Keywords: Other arthropods
Genetically modified mice could fight Lyme disease in Massachusetts
35429Dave Puglisi, 7News, 2026-01-29 10:43:05.
Tiny insects are spreading a devastating disease. Scientists at Massachusetts Institute of Technology (MIT) believe they’ve discovered something that could help stop Lyme disease before it starts. “The right side of my body went numb. I felt disoriented. My heart was racing,” said Brandi Dean. Dean thought what she was experiencing was a stroke but it was actually the start of a 10-year battle with Lyme disease. “It’s a devastating illness, emotionally, physically, and financially,” she said. The illness began with a tick bite that spread bacteria throughout her body. “I was really struggling to just survive every day and to take care of my kids,” said Dean. Brandi pushed through muscle pain, dizziness and exhaustion so severe she couldn’t walk down the stairs. “I would literally scoot down each stair. I had very little energy to walk,” said Dean. “It was frightening at that time.” Doctor Sam Telford, a professor of infectious disease and global health at Tufts University, has studied ticks for more than 40-years. He says mice are a perfect host for several diseases ticks can spread. “They’re very good hosts for the bacteria. They suffer no disease from having the bacteria,” said Telford. “They pass it back-and-forth and us humans are collateral damage.”
Sterile insect technique reduces cabbage maggot (Diptera: Anthomyiidae) infestation in root crucifers in Canada
35337Anne-Marie Fortier, Allen Bush-Beaupré, Jade Savage, et al., Journal of Economic Entomology, 118:2710–2717. 2026-01-07 11:20:58.
The cabbage maggot (Delia radicum (L.)) is a major pest of brassica vegetables in Canada that has traditionally been managed with soil-applied insecticides. However, recent regulatory restrictions on key products such as chlorpyrifos have created a pressing need for alternative solutions. This study evaluates the sterile insect technique (SIT) as a control method for the cabbage maggot in root crucifers. Large-scale field trials conducted from 2019 to 2022 in Quebec (Canada) demonstrated significant reductions in D. radicum infestations in radish and daikon crops. Quality control measures confirmed the effectiveness of sterilization on cabbage maggot, with minimal impact on male performance. The results suggest that the SIT is a promising, environmentally friendly alternative to chemical control for cabbage maggot management. The study further highlights the importance of optimizing release strategies and improving predictive models to guide deployment. Overall, the SIT offers growers a viable option to reduce reliance on insecticides while maintaining crop health and yield.
A comprehensive review of biological and genetic control approaches for leishmaniasis vector sand flies; emphasis towards promoting tools for integrated vector management
34611Kumari, Y., Gunathilaka, N., Amarasinghe, D., PLOS Neglected Tropical Diseases, 19. 2025-01-27 11:07:43.
Leishmaniasis is a health problem in many regions with poor health and poor life resources. According to the World Health Organization (WHO), an estimated 700,000–1 million new cases arise annually. Effective control of sand fly vector populations is crucial for reducing the transmission of this disease. Therefore, this review aims to comprehensively examine and evaluate the current methods for controlling sand fly populations, focusing on biological and gene drive techniques. A detailed, comprehensive literature search was carried out using databases including Google Scholar, PubMed, ScienceDirect, and the National Library of Medicine (NIH). These searches were done using specific keywords related to the field of study. This current review identified several promising methods, including genetically modified sand flies, using transgenic approaches by taking advanced gene editing tools like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) and genetic modification of symbiotic microorganisms for controlling sand fly populations, which appeared to be proven under laboratory and field settings. Genetic control approaches have many benefits over chemical control, including long-lasting effects on targets, high specificity, and less environmental impact. Advances in genetic engineering technologies, particularly CRISPR/Cas9, sterile insect techniques, and gene drive insect modification, offer new avenues for precise and efficient sand fly management. Future research should prioritize optimizing rearing and sterilization techniques, conducting controlled field trials, and fostering collaboration across disciplines to realize the potential of genetic control strategies in combating leishmaniasis.
Biased social chromosome transmission in males of the fire ant Solenopsis invicta
34049Daniel R Hettesheimer, Haolin Zeng, Brendan G Hunt, Kenneth G Ross, G3: Genes|Genomes|Genetics, 2024-12-16 14:21:28.
Selfish genetic elements subvert the normal rules of inheritance to unfairly propagate themselves, often at the expense of other genomic elements and the fitness of individuals carrying them. Social life provides diverse avenues for the propagation of such elements. In the fire ant Solenopsis invicta, polymorphic social organization is controlled by a social chromosome, one variant of which (Sb) enhances its own transmission in polygyne colonies through effects on caste development and queen acceptance by workers. Whether the selfish effects of Sb extend to haploid (reproductive) males in this system is less clear. Here, we demonstrate a strong overrepresentation of the Sb social chromosome haplotype in reproductive males, relative to Mendelian expectations, in both the pupal and adult stages. We tested for the presence of selective execution of adult SB males by workers but did not detect such behavior. Combined with the presence of a strong imbalance in the haplotype frequencies already early in the pupal stage, these results indicate that the Sb supergene may distort male haplotype frequencies during larval or embryonic development. These findings are significant because they demonstrate yet another mode by which the selfish tendencies of the Sb supergene are manifested, illuminate complex interactions between Sb and the fire ant breeding system, inform the development of models of the population dynamics of Sb, and illustrate how a selfish supergene can increase in frequency in a population despite harboring deleterious mutations.
To CRISPR or Not to CRISPR? Ethical Considerations in Gene-Editing Insects
31614Brendan Parent, Meghan Barrett, American Entomologist, 70:54-57. 2024-09-18 21:33:47.
Genetically modified corn has helped feed the world (Hernandes-Lopes et al. 2023). Genetically modified mosquitoes could help eliminate devastating diseases like malaria (Hammond and Galizi 2017). Plainly, gene editing can serve some important human interests. Still, many people object to it. While some concerns have little scientific validity, there are valid ethical concerns that should be addressed. A concern many people share is the potential impact of genetically edited insects on the environment. Gene drives are “selfish” genetic elements that are transmitted to progeny at unusually high rates and thus spread rapidly through populations. As a result, they are capable of modifying an entire population or species. The most widely discussed use of gene drives is in the prevention of malaria, the leading cause of human illness and death in many parts of the world (CDC 2021), where gene drives could be used to control mosquito populations. At present, however, there are no sure-fire strategies to “recall” a gene drive once it has been released (Hammond and Galizi 2017). Given the many unintended environmental impacts of other technological advancements and our uncertainties about the impacts of using gene drives (Ahmad et al. 2022), it makes sense to have similar concerns about this form of gene editing. Granted, it is possible that the extraordinary benefits to human life of such a gene drive, if successful, outweigh the risks of any unintended environmental consequences. This is particularly likely to be true if convincing measures like “terminator genes” can be employed to control genetically edited insect populations in the wild (Hammond et al. 2021). Given the serious promise and ethical concerns of this technology, the National Academy of Sciences has published guidelines for responsible research that include self-governance and government regulation, evaluating gene drives on a case-by-case basis (NASEM 2016). So, while risks of environmental harm are important, we can now see how they might not be decisive: first, the corresponding benefits might be very weighty; second, the risks might be mitigable.
What if GM mosquitoes could help limit the tiger mosquito population?
31311Anonymous, All News Press, 2024-09-03 15:23:03.
What if the fight against the tiger mosquito, this invasive species originating from Southeast Asia and established in France for about twenty years, was not totally lost in advance? The exploratory project of Éric Marois, research officer Inserm, within the Institute of Molecular and Cellular Biology (CNRS) in Strasbourgoffers some hope. This fundamental biology researcher explains to 20 Minutes that thanks to Crispr/Cas9 molecular scissors it is possible to cut DNA at a specific location to create a transgenic mosquito. This will either transform female tiger mosquitoes into males or make their offspring sterile. To sort the insects thus modified, they are made fluorescent in the laboratory. An update on this work, funded for at least four years by the national research agency and which could make headlines in the coming years. Genetic engineering, or the idea of using genetic elements to modify the characteristics of mosquitoes, dates back to the 1960s. But at the time, there were no tools at all to carry it out in the laboratory. It was in 2012, with the discovery of the Crispr/Cas9 molecular scissors, which earned Emmanuelle Charpentier and Jennifer Doudna the Nobel Prize in Chemistry, that its application was truly made possible. It involves artificially producing a guide RNA (as exists in nature) and thus directing the Cas9 protein to a chosen DNA sequence within the desired genome.
Wolbachia symbionts control sex in a parasitoid wasp using a horizontally acquired gene
29885Li C, Li CQ, Chen ZB, Liu BQ, Sun X, Wei KH, Li CY, Luan JB., Current Biology, 2024-05-07 15:55:59.
Host reproduction can be manipulated by bacterial symbionts in various ways. Parthenogenesis induction is the most effective type of reproduction manipulation by symbionts for their transmission. Insect sex is determined by regulation of doublesex (dsx) splicing through transformer2 (tra2) and transformer (tra) interaction. Although parthenogenesis induction by symbionts has been studied since the 1970s, its underlying molecular mechanism is unknown. Here we identify a Wolbachia parthenogenesis-induction feminization factor gene (piff) that targets sex-determining genes and causes female-producing parthenogenesis in the haplodiploid parasitoid Encarsia formosa. We found that Wolbachia elimination repressed expression of female-specific dsx and enhanced expression of male-specific dsx, which led to the production of wasp haploid male offspring. Furthermore, we found that E. formosa tra is truncated and non-functional, and Wolbachia has a functional tra homolog, termed piff, with an insect origin. Wolbachia PIFF can colocalize and interact with wasp TRA2. Moreover, Wolbachia piff has coordinated expression with tra2 and dsx of E. formosa. Our results demonstrate the bacterial symbiont Wolbachia has acquired an insect gene to manipulate the host sex determination cascade and induce parthenogenesis in wasps. This study reveals insect-to-bacteria horizontal gene transfer drives the evolution of animal sex determination systems, elucidating a striking mechanism of insect-microbe symbiosis.
A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance
28651Jingheng Chen, Shibo Hou, Ruobing Feng, Xuejiao Xu, Nan Liang, Jackson Champer, bioRxiv, 2023-12-05 10:59:48.
CRISPR homing gene drive is a potent technology with considerable potential for managing populations of medically and agriculturally significant insects. It induces a bias in the inheritance of the drive allele in progeny, rapidly spreading desired genes throughout the population. Homing drives operate by Cas9 cleavage followed by homology-directed repair, copying the drive allele to the wild-type chromosome. However, resistance alleles formed by end-joining repair pose a significant obstacle to the spread of the drive. To address this challenge, we created a homing drive targeting the essential but haplosufficient hairy gene. Our strategy involves spreading the drive construct through the homing process, eliminating nonfunctional resistance, which are recessive lethal, while rescuing drive-carrying individuals with a recoded version of hairy. This strategy eliminates resistance more slowly than a previous strategy targeting haplolethal genes, but it may be easier to construct in non-model organisms. Our drive inheritance rate was moderate, and multigenerational cage studies showed quick drive spread to 96-97% of the population. However, the drive failed to reach the whole population due to the formation of functional resistance alleles, despite use of four gRNAs, a strategy that previously was successful at preventing functional resistance. Sequencing showed that these alleles had a large deletion and must have utilized an alternate start codon. The resistance allele had a modest fitness advantage over the drive in a cage study, which could prevent long-term persistence of the drive, especially if cargo genes had an additional fitness cost. Thus, revised design strategies targeting more essential regions of a target gene may often be necessary to avoid such functional resistance, even when using multiplexed gRNAs.
How to fight insects that transmit diseases to people without harming those who cannot?
28157Nation World News Desk, Nation World, 2023-10-20 11:55:16.
One way to avoid this severe environmental impact is to specifically control the population of species that cause problems. This can be done chemically by releasing hormones into the environment that prevent passage to the adult stage, or pheromones that make them believe that a beautiful insect is waiting for them ready for sex, when in fact they fell in the trap of death. The problem with these methods is that sometimes the required molecules are very expensive and not always specific to what we want. A more effective strategy is to sterilize the population of male insects with radioactivity. In nature, these males mate with females, but cannot produce children. This technique has been used for a long time with reasonable results, although it is not 100% effective and the use of radioactivity means the appearance of mutations and it may happen (unlikely) that some give some development for the insect, and a recurring problem for us.However, genetic engineering offers us help. CRISPR/Cas9 is a technology that allows us to make specific changes in a specific area of the genome of any living organism. We can give it a twist and, instead of applying this technique to the genome of an insect by making a specific modification, what we do is modify an insect so that its genome has everything it needs to activate CRISPR/Cas9. time and cause sterility. It’s like hiding in your genome a complete CRISPR/Cas9 kit and the instructions to change a specific gene to create sterility. What is the advantage? If we only disperse the sterile males, those that are not sterile (sterilization is never 100% and we have to compete with the native population) will continue to reproduce, and in a few generations the effect will disappear.
X-rays are as effective as gamma-rays for the sterilization of Glossina palpalis gambiensis Vanderplank, 1911 (Diptera: Glossinidae) for use in the sterile insect technique
28223B. A. Kaboré, A. Nawaj, H. Maiga, O. Soukia, S. Pagabeleguem, M. S. G. Ouédraogo/Sanon, M. J. B. Vreysen, R. L. Mach and C. J. de Beer, Scientific Reports, 13:17633. 2023-10-17 15:00:27.
An area-wide integrated pest management strategy with a sterile insect technique (SIT) component requires a radiation source for the sterilisation of male insects. Self-contained gamma irradiators, which were exclusively used in past SIT programmes, are now facing increasing constraints and challenges due to stringent regulations. As a potential alternative, new generation high output X-ray irradiators have been proposed. The feasibility of using X-ray irradiators was assessed by comparing the effects of both gamma- and X-ray irradiators on biological parameters of Glossina palpalis gambiensis (Vanderplank, 1911), that are important for SIT applications. The gamma irradiator Foss Model 812 and two X-ray irradiators, the Rad Source 2400 and the blood irradiator Raycell Mk2 were used. Glossina palpalis gambiensis males were exposed to radiation as pupae. A radiation dose of 110 Gy or above induced more than 97% sterility in females that mated with the irradiated males for all the irradiators. Adult emergence rate, flight propensity, survival and mating performance did not differ between gamma- and X-rays irradiators. These results suggest that irradiating pupae with a dose of 110 Gy is optimal for both gamma-and X-ray irradiators used in this study, to achieve a sterility of approximately 99%. Similar research on other tsetse species could gradually phase out the use of gamma-ray irradiators in favour of X-rays irradiators, especially for smaller SIT programmes.
Development and characterization of microsatellite markers for the tsetse species Glossina brevipalpis and preliminary population genetics analyses
27882F. Gstöttenmayer, P. Moyaba, M. Rodriguez, F. C. Mulandane, H. N. Mucache, L. Neves, C. De Beer, S. Ravel, T. De Meeûs, R. L. Mach, M. J. B. Vreysen and A. M. M. Abd-Alla, Parasite, 30:34. 2023-09-15 08:27:06.
Tsetse flies, the vectors of African trypanosomes are of key medical and economic importance and one of the constraints for the development of Africa. Tsetse fly control is one of the most effective and sustainable strategies used for controlling the disease. Knowledge about population structure and level of gene flow between neighbouring populations of the target vector is of high importance to develop appropriate strategies for implementing effective management programmes. Microsatellites are commonly used to identify population structure and assess dispersal of the target populations and have been developed for several tsetse species but were lacking for Glossina brevipalpis. In this study, we screened the genome of G. brevipalpis to search for suitable microsatellite markers and nine were found to be efficient enough to distinguish between different tsetse populations. The availability of these novel microsatellite loci will help to better understand the population biology of G. brevipalpis and to assess the level of gene flow between different populations. Such information will help with the development of appropriate strategies to implement the sterile insect technique (SIT) in the framework of an area-wide integrated pest management (AW-IPM) approach to manage tsetse populations and ultimately address the trypanosomoses problem in these targeted areas.
Influence of environmental conditions on mass rearing parameters of tsetse flies at the Bobo-Dioulasso insectary (Burkina Faso): retrospective study
27966K. S. M. Dera, B. A. Kaboré, S. Pagabeleguem, A. A. Ouedraogo, A. I. Toé, M. Ira, A. M. G. Belem and G. M. S. O. Sanou, International Journal of Biological and Chemical Sciences, 17:1020-1032. 2023-08-24 07:18:58.
With the goal of eradicating tsetse flies and trypanosomiasis in Africa, several control methods have been developed. One of this is the biological control through the application of the sterile insect technique (SIT) as a part of an area-wide integrated pest management. This method required the mass production of sterile males with a high competitiveness. The success of the tsetse mass rearing is strongly linked to the rearing conditions. The objective of this study was to do a retrospective evaluation of the impact of ambient conditions on the production performances of Glossina palpalis gambiensis at Insectary of Bobo Dioulasso. Data of productivity, fecundity, adult emergence and environmental conditions (temperature and relative humidity) of the rearing rooms were recorded from March to June 2020 and were analysed. The results showed a reduction of the normal pupae produced and the increase of soft pupae during this period. In addition, the relative humidity has shown a significant positive correlation with the production of soft pupae, whereas it had a significant negative correlation with the number of pupae produced per female per 10 days. However, the temperature variation during the period of the data recording didn’t have any impact on the production parameters. Rearing rooms need a better management to avoid large variations in environmental parameters. © 2023 International Formulae Group. All rights reserved.
Gene drives for invasive wasp control: Extinction is unlikely, with suppression dependent on dispersal and growth rates
27669P. J. Lester, D. O'Sullivan and G. L. W. Perry, Ecological Applications, 2023-08-24 06:36:30.
Abstract Gene drives offer a potentially revolutionary method for pest control over large spatial extents. These genetic modifications spread deleterious variants through a population and have been proposed as methods for pest suppression or even eradication. We examined the influence of local dispersal, long-distance and/or human-mediated dispersal, and variation in population growth, on the success of a gene drive for the control of invasive social wasps (Vespula vulgaris). Our simulations incorporated a spatially realistic environment containing variable habitat quality in New Zealand. Pest eradication was not observed, except in extreme and unrealistic scenarios of constant, widespread, and spatially intense releases of genetically modified individuals every year for decades. Instead, the regional persistence of genetically modified and wild-type wasps was predicted. Simulations using spatially homogeneous versus realistic landscapes (incorporating uninhabitable areas and dispersal barriers) showed little difference in overall population dynamics. Overall, little impact on wasp abundance was observed in the first 15?years post-introduction. After 25?years, populations were suppressed to levels <95% of starting populations. Populations exhibited ?chase dynamics? with population cycles in space, with local extinction occurring in some areas while wasps became abundant in others. Increasing the wasps' local dispersal distance increased the spatial and temporal variability of the occupied area and population suppression. Varying levels of human-associated long-distance dispersal had little effect on population dynamics. Increasing intrinsic population growth rates interacted with local dispersal to cause higher mean populations and substantially higher levels of variation in population suppression and the total amount of landscape occupied. Gene drives appear unlikely to cause a rapid and widespread extinction of this and probably other pests, but could offer long-term and cost-effective methods of pest suppression. The predicted level of <95% pest suppression would substantially reduce the predation pressure and competitive interactions of this invasive wasp on native species. However, the predicted long-term persistence of genetically modified pests will influence the ethics and likelihood of using gene drives for pest control, especially given concerns that modified wasps would eventually be transported back to their home range.
Ability of a selfish B chromosome to evade genome elimination in the jewel wasp, Nasonia vitripennis
27561H. Lee, P. Seo, S. Teklay, E. Yuguchi, E. D. Benetta, J. H. Werren and P. M. Ferree, Heredity, 2023-07-31 07:06:11.
B chromosomes are non-essential, extra chromosomes that can exhibit transmission-enhancing behaviors, including meiotic drive, mitotic drive, and induction of genome elimination, in plants and animals. A fundamental but poorly understood question is what characteristics allow B chromosomes to exhibit these extraordinary behaviors. The jewel wasp, Nasonia vitripennis, harbors a heterochromatic, paternally transmitted B chromosome known as paternal sex ratio (PSR), which causes complete elimination of the sperm-contributed half of the genome during the first mitotic division of fertilized embryos. This genome elimination event may result from specific, previously observed alterations of the paternal chromatin. Due to the haplo-diploid reproduction of the wasp, genome elimination by PSR causes female-destined embryos to develop as haploid males that transmit PSR. PSR does not undergo self-elimination despite its presence with the paternal chromatin until the elimination event. Here we performed fluorescence microscopic analyses aimed at understanding this unexplained property. Our results show that PSR, like the rest of the genome, participates in the histone-to-protamine transition, arguing that PSR does not avoid this transition to escape self-elimination. In addition, PSR partially escapes the chromatin-altering activity of the intracellular bacterium, Wolbachia, demonstrating that this ability to evade chromatin alteration is not limited to PSR's own activity. Finally, we observed that the rDNA locus and other unidentified heterochromatic regions of the wasp's genome also seem to evade chromatin disruption by PSR, suggesting that PSR's genome-eliminating activity does not affect heterochromatin. Thus, PSR may target an aspect of euchromatin to cause genome elimination.
X chromosome drive is constrained by sexual selection and influences ornament evolution
27304K. A. Paczolt, G. T. Welsh and G. S. Wilkinson, Proceedings of the Royal Society B: Biological Sciences, 290:20230929. 2023-07-26 07:17:43.
Experimental evolution provides an integrative method for revealing complex interactions among evolutionary processes. One such interaction involves sex-linked selfish genetic elements and sexual selection. X-linked segregation distorters, a type of selfish genetic element, influence sperm transmission to increase in frequency and consequently alter the population sex ratio and the opportunity for sexual selection, while sexual selection may impact the spread of X-linked distorters. Here we manipulated sexual selection by controlling female mating opportunities and the presence of a distorting X chromosome in experimental lines of the stalk-eyed fly, Teleopsis dalmanni, over 11 generations. We find that removal of sexual selection leads to an increase in the frequency of the X-linked distorter and sex ratio across generations and that post-copulatory sexual selection alone is sufficient to limit the frequency of distorters. In addition, we find that male eyestalk length, a trait under pre-copulatory sexual selection, evolves in response to changes in the strength of sexual selection with the magnitude of the response dependent on X chromosome type and the frequency of distorting X chromosomes. These results reveal how a selfish X can interact with sexual selection to influence the evolution of sexually selected traits in multiple ways.
Impacts of sex ratio meiotic drive on genome structure and function in a stalk-eyed fly
26279J. A. Reinhardt, R. H. Baker, A. V. Zimin, C. Ladias, K. A. Paczolt, J. H. Werren, C. Y. Hayashi and G. S. Wilkinson, Genome Biology Evolution, 2023-06-26 10:49:44.
Stalk-eyed flies in the genus Teleopsis carry selfish genetic elements that induce sex ratio meiotic drive (SR) and impact the fitness of male and female carriers. Here, we assemble and describe a chromosome-level genome assembly of the stalk-eyed fly, Teleopsis dalmanni, to elucidate patterns of divergence associated with SR. The genome contains tens of thousands of transposable element (TE) insertions and hundreds of transcriptionally and insertionally active TE families. By resequencing pools of SR and ST males using short and long-reads, we find widespread differentiation and divergence between XSR and XST associated with multiple nested inversions involving most of the sex ratio haplotype. Examination of genomic coverage and gene expression data revealed seven X-linked genes with elevated expression and coverage in SR males. The most extreme and likely drive candidate involves an XSR-specific expansion of an array of partial copies of JASPer, a gene necessary for maintenance of euchromatin and associated with regulation of TE expression. In addition, we find evidence for rapid protein evolution between XSR and XST for testis expressed and novel genes, i.e. either recent duplicates or lacking a dipteran ortholog, including an X-linked duplicate of maelstrom, which is also involved in TE silencing. Overall, the evidence suggests that this ancient XSR polymorphism has had a variety of impacts on repetitive DNA and its regulation in this species.
Oxitec Launches New Technology Program to Develop a Friendly™ Solution for the World’s Most Damaging Cattle Tick
25292Oxitec Ltd, Oxitec Press Release, 2023-05-24 07:45:30.
Oxitec Ltd, the leading developer of insect-based biological solutions to control pests that transmit disease, destroy crops and harm livestock, today announced the launch of development of a targeted, biological Friendly™ solution for the world’s most devastating cattle pest, the Asian blue tick, or Rhipicephalus microplus. In a feasibility project funded by the Bill & Melinda Gates Foundation, Oxitec’s team validated the key methods for development of a Friendly™ R. microplus, and found that, for management of this dangerous tick, this biological approach is anticipated to provide a highly effective alternative to chemical pesticides. The Foundation has now committed $4.8 million to an early development phase to start to build the Friendly™ R. microplus solution, Oxitec’s first targeting a non-insect pest.
Near-infrared imaging for automated tsetse pupae sex sorting in support of the sterile insect technique
25472R. Argilés-Herrero, G. Salvador-Herranz, A. G. Parker, M. Zacarés, A. G. Fall, A. M. Gaye, A. Nawaz, P. Takáč, M. J. B. Vreysen and C. J. de Beer, Parasite, 30. 2023-05-17 08:49:45.
Tsetse flies are the cyclical vectors of African trypanosomes and one of several methods to manage this vector is the sterile insect technique (SIT). The ability to determine the sex of tsetse pupae with the objective to separate the sexes before adult emergence has been a major goal for decades for tsetse management programmes with an SIT component. Tsetse females develop faster and pharate females inside the pupae melanise 1–2 days before males. This earlier melanisation can be detected by infrared cameras through the pupal shell, and the newly developed Near InfraRed Pupae Sex Sorter (NIRPSS) takes advantage of this. The melanisation process is not homogeneous for all fly organs and the pupa needs to be examined ventrally, dorsally and laterally to ensure accurate classification by an image analysis algorithm. When the pupae are maturing at a constant temperature of 24 °C and sorted at the appropriate age, 24 days post-larviposition for Glossina palpalis gambiensis, the sorting machine can efficiently separate the sexes. The recovered male pupae can then be sterilised for field releases of males, while the rest of the pupae can be used to maintain the laboratory colony. The sorting process with the new NIRPSS had no negative impact on adult emergence and flight ability. A mean male recovery of 62.82 ± 3.61% was enough to provide sterile males to an operational SIT programme, while mean contamination with females (4.69 ± 3.02%) was low enough to have no impact on the maintenance of a laboratory colony
Evaluating the Effect of Irradiation on the Densities of Two RNA Viruses in Glossina morsitans morsitans
25137C. K. Mirieri, A. M. M. Abd-Alla, V. I. D. Ros and M. M. van Oers, Insects, 14. 2023-04-20 14:11:24.
Tsetse flies are cyclic vectors of Trypanosoma parasites, which cause debilitating diseases in humans and animals. To decrease the disease burden, the number of flies is reduced using the sterile insect technique (SIT), where male flies are sterilized through irradiation and released into the field. This procedure requires the mass rearing of high-quality male flies able to compete with wild male flies for mating with wild females. Recently, two RNA viruses, an iflavirus and a negevirus, were discovered in mass-reared Glossina morsitans morsitans and named GmmIV and GmmNegeV, respectively. The aim of this study was to evaluate whether the densities of these viruses in tsetse flies are affected by the irradiation treatment. Therefore, we exposed tsetse pupae to various doses (0–150 Gy) of ionizing radiation, either in air (normoxia) or without air (hypoxia), for which oxygen was displaced by nitrogen. Pupae and/or emerging flies were collected immediately afterwards, and at three days post irradiation, virus densities were quantified through RT-qPCR. Generally, the results show that irradiation exposure had no significant impact on the densities of GmmIV and GmmNegeV, suggesting that the viruses are relatively radiation-resistant, even at higher doses. However, sampling over a longer period after irradiation would be needed to verify that densities of these insect viruses are not changed by the sterilisation treatment. © 2023 by the authors.
Gamma-radiation of Glossina palpalis gambiensis revisited: effect on fertility and mating competitiveness
24993S. Pagabeleguem, O. Koughuindida, E. W. Salou, G. Gimonneau, A. I. Toé, B. A. Kaboré, K. S. M. Dera, H. Maïga, A. M. G. Belem, G. M. S. Sanou/Ouédraogo, M. J. Vreysen and J. Bouyer, Parasite, 30:8. 2023-03-31 14:58:29.
African animal trypanosomoses are vector-borne diseases that cause enormous livestock losses in sub-Saharan Africa, with drastic socio-economic impacts. Vector control in the context of an area-wide integrated pest management program with a sterile insect technique component requires the production of high-quality sterile male tsetse flies. In our study, we evaluated the effect of irradiation on the fecundity of Glossina palpalis gambiensis to identify the optimal dose that will induce maximum sterility while maintaining biological performance as much as possible. In addition, male mating performance was evaluated in semi-field cages. The irradiation doses used were 90, 100, 110, 120, 130, 140, and 150 Gy, and untreated males were used as the control. The results showed that pupal production and emergence rates were higher in batches of females that had mated with fertile males than in those that had mated with irradiated males with any experimental dose. A dose of 120 Gy administered to male flies induced 97-99% sterility after mating with virgin females. For the semi-field cage experiments, males irradiated with 120 Gy showed good sexual competitiveness as compared to fertile males and those irradiated with 140 Gy, considering the level of filling of spermatheca and the number of pairs formed. The optimal radiation dose of 120 Gy found in this study is slightly different from the traditional dose of 110 Gy that has been used in several eradication programmes in the past. The potential reasons for this difference are discussed, and an argument is made for the inclusion of reliable dosimetry systems in these types of studies.
Vector competence of sterile male Glossina fuscipes fuscipes for Trypanosoma brucei brucei: implications for the implementation of the sterile insect technique in a sleeping sickness focus in Chad
24883M. H. Mahamat, A. Ségard, J.-B. Rayaisse, R. Argiles-Herrero, A. G. Parker, P. Solano, A. M. M. Abd-Alla, J. Bouyer and S. Ravel, Parasites and Vectors, 16:111. 2023-03-22 07:59:24.
Human African trypanosomiasis (HAT) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by tsetse flies in sub‑Saharan West Africa. In southern Chad the most active and persistent focus is the Mandoul focus, with 98% of the reported human cases, and where African animal trypanosomosis (AAT) is also present. Recently, a control project to eliminate tsetse flies (Glossina fuscipes fuscipes) in this focus using the sterile insect technique (SIT) was initiated. However, the release of large numbers of sterile males of G. f. fuscipes might result in a potential temporary increase in transmission of trypanosomes since male tsetse flies are also able to transmit the parasite. The objective of this work was therefore to experimentally assess the vector competence of sterile males treated with isometamidium for Trypanosoma brucei brucei.
Engineered symbiotic bacteria interfering Nosema redox system inhibit microsporidia parasitism in honeybees
24493H. Lang, H. Wang, H. Wang, X. Xie, X. Hu, X. Zhang and H. Zheng, bioRxiv, 2023.01.13.524015. 2023-01-14 16:42:03.
Nosema ceranae is an emergent microsporidia parasite of the European honey bee (Apis mellifera), which causes serious nosemosis implicated in honeybee colony losses worldwide. N. ceranae is an obligate intracellular eukaryotic parasite that mainly invades the midgut of honeybees. Recent studies find that bee gut microbiota is potentially involved in protecting against parasitism. Here, using laboratory-generated bees mono-associated with gut members, we find that Snodgrassella alvi inhibited microsporidia proliferation, potentially via the stimulation of host oxidant-mediated immune response. Accordingly, N. ceranae employs the thioredoxin and glutathione systems to defend against oxidative stress and maintain a balanced redox equilibrium, which is essential for the infection process. We knocked down the gene expression using nanoparticle-mediated RNA interference, which targets the γ-glutamyl-cysteine synthetase and thioredoxin reductase genes of microsporidia. It significantly reduces the spore load, confirming the importance of the antioxidant mechanism for the intracellular invasion of the N. ceranae parasite. Finally, we genetically modified the symbiotic S. alvi to deliver dsRNA corresponding to the genes involved in the redox system of the microsporidia. The engineered S. alvi induces RNA interference and represses parasite gene expression, thereby inhibits the parasitism by up to 99.8%. Specifically, N. ceranae was most suppressed by the recombinant strain corresponding to the glutathione synthetase or by a mixture of bacteria expressing variable dsRNA. Our findings extend our previous understanding of the protection of gut symbionts against N. ceranae and provide a symbiont-mediated RNAi system for inhibiting microsporidia infection in honeybees.Competing Interest StatementThe authors have declared no competing interest.
Cell-based analysis reveals that sex-determining gene signals in Ostrinia are pivotally changed by male-killing Wolbachia
24288B. Herran, T. N. Sugimoto, K. Watanabe, S. Imanishi, T. Tsuchida, T. Matsuo, Y. Ishikawa and D. Kageyama, PNAS Nexus, pgac293. 2022-12-13 08:59:49.
Wolbachia, a maternally transmitted bacterium, shows male-killing, an adaptive phenotype for cytoplasmic elements, in various arthropod species during the early developmental stages. In lepidopteran insects, lethality of males is accounted for by improper dosage compensation in sex-linked genes owing to Wolbachia-induced feminization. Herein, we established Ostrinia scapulalis cell lines that retained sex specificity per the splicing pattern of the sex-determining gene doublesex (Osdsx). We found that Wolbachia transinfection in male cell lines enhanced the female-specific splice variant of Osdsx (OsdsxF) while suppressing the male-specific variant (OsdsxM), indicating that Wolbachia affects sex-determining gene signals even in vitro. Comparative transcriptome analysis isolated only two genes that behave differently upon Wolbachia infection. The two genes were respectively homologous to Masculinizer (BmMasc) and zinc finger-2 (Bmznf-2), male-specifically expressed sex-determining genes of the silkworm Bombyx mori that encode CCCH-type zinc finger motif proteins. By using cultured cells and organismal samples, OsMasc and Osznf-2 were found to be sex-determining genes of O. scapulalis that are subjected to sex-specific alternative splicing depending upon the chromosomal sex, developmental stage, and infection status. Overall, our findings expound the cellular autonomy in insect sex determination and the mechanism through which sex is manipulated by intracellular selfish microbes.
Meiotic drive does not impede success in sperm competition in the stalk-eyed fly, Teleopsis dalmanni
23566S. Bates, L. Meade and A. Pomiankowski, bioRxiv, 2022-09-13 15:00:24.
Meiotic drive genes are selfish genetic elements that distort Mendelian patterns of inheritance to bias transmission in their favour. We use the stalk-eyed fly, Teleopsis dalmanni, to investigate the fitness effects associated with a meiotic drive gene called Sex Ratio (SR), which is linked to the X chromosome. In males, SR destroys Y-bearing sperm, meaning only X-bearing sperm are viable, and females who mate with drive males sire all-female broods. This confers a two-fold transmission advantage to the SR gene, as it is transmitted to all offspring.We recently discovered that drive males have evolved compensatory mechanisms to cope with the sperm destruction caused by meiotic drive. They have greatly enlarged testes, allowing them to produce more sperm. When drive males mate with females, they deliver as many sperm and sire as many offspring as wildtype males. Building on this finding, we measured how drive male sperm performs against sperm from a non-carrier male in sperm competition – where the sperm from different males compete to fertilise an egg. Double mating trials were performed, where a single female was mated once to a drive and once to a non-carrier male. By genotyping offspring, we show that the number of offspring sired by the drive male was not different from the number sired by the non-carrier competitor.These findings contrast with those in other species. Typically, drive males do poorly in sperm competition and their spread is severely restricted by sperm competition. In stalk-eyed flies, female multiple mating with many males is the norm, but this does not appear to inhibit the fertility of drive males. The success of drive under sperm competition helps to explain the high frequency of drive around 20% in natural populations of T. dalmanni.Competing Interest StatementThe authors have declared no competing interest.
Genetic Tools for Integrated Management of Pests on Honeybees in the Tropics
25464M. Pattabhiramaiah, S. Mallikarjunaiah and D. Brueckner, Genetic Methods and Tools for Managing Crop Pests, 2022-08-22 09:48:31.
The Asian honeybee is endemic to Asia where it has been used for honey production and pollination services from time immemorial. They are integral to modern agricultural productivity and to survival and vitality of natural ecosystems. However, recent declines in populations and species diversity threaten both food security and natural habitats. Honeybee colonies are assaulted by numerous pests and pathogens including mites and beetles. Novel, cost-effective pest management practices are desperately needed to preserve colony health. Increased pest pressure levels justify the need for additional control methods. Beekeepers should follow the guidelines of integrated pest management (IPM) as an effective control option that will have a minimum impact on honeybee health. The use of genomic tools and engineering technologies has a great potential for enhancement and sustenance of the health of honeybees. This review focusses on the application of innovative advanced genetic tools such as SIT (sterile insect technique), genome editing, gene drive, RNAi, CRISPR/Cas9-mediated gene editing, and gene pyramiding in honeybee pest management.
Reflection on the Challenges, Accomplishments, and New Frontiers of Gene Drives
23416M. Melesse Vergara, J. Labbé and J. Tannous, BioDesign Research, 2022:9853416. 2022-08-09 07:29:59.
Ongoing pest and disease outbreaks pose a serious threat to human, crop, and animal lives, emphasizing the need for constantgenetic discoveries that could serve as mitigation strategies. Gene drives are genetic engineering approaches discovered decadesago that may allow quick, super-Mendelian dissemination of genetic modifications in wild populations, offering hopes formedicine, agriculture, and ecology in combating diseases. Following itsfirst discovery, several naturally occurring selfishgenetic elements were identified and several gene drive mechanisms that could attain relatively high threshold populationreplacement have been proposed. This review provides a comprehensive overview of the recent advances in gene drive researchwith a particular emphasis on CRISPR-Cas gene drives, the technology that has revolutionized the process of genomeengineering. Herein, we discuss the benefits and caveats of this technology and place it within the context of natural genedrives discovered to date and various synthetic drives engineered. Later, we elaborate on the strategies for designing syntheticdrive systems to address resistance issues and prevent them from altering the entire wild populations. Lastly, we highlight themajor applications of synthetic CRISPR-based gene drives in different living organisms, including plants, animals, andmicroorganisms.
Quality Control and Mating Performance of Irradiated Glossina palpalis gambiensis Males
22546K. Ilboudo, K. Camara, E. W. Salou and G. Gimonnea, Insects, 13. 2022-05-19 08:04:34.
The biological quality of sterile male insects produced in a mass-rearing facility is a prerequisite for the success of the SIT, which is a component of area-wide integrated pest management (AW-IPM). Indeed, sterile male insects released in the field must have a good mating performance in order to compete with wild males, but they must also present the required level of sterility. In the present study, the biological quality of sterile male Glossina palpalis gambiensis produced in a mass-rearing insectary was assessed through quality control testing. The mating performance of irradiated males was assessed in walk-in field cages. Irradiation had no effect on adult emergence but significantly reduced the percentage of operational flies (from 89.58% to 79.87%) and male survival (from 5 to 4 days, on average). However, irradiation did not impact the sterile male insemination potential, with all females inseminated and more than 80% of the spermathecae completely filled. The rate of induced sterility in females was 89.67% due to a dose rate decrease of the radiation source. Moreover, sterile males were able to compete successfully with untreated fertile males for untreated females in walk-in field cages. This study confirmed that the flies were still competitive and stressed the importance of regularly checking the radiation source parameters.
Wolbachia Impacts Anaplasma Infection in Ixodes scapularis Tick Cells
20436K. M. Skinner, J. Underwood, A. Ghosh, A. S. Oliva Chavez and C. L. Brelsfoard, International Journal of Environmental Research and Public Health, 19. 2022-02-16 08:58:32.
The specific interactions of members of tick bacterial microbiota and their effects on pathogen transmission remains relatively unexplored. Here, we introduced a novel Wolbachia infection type into Ixodes scapularis tick cells and examined the antipathogenic effects on the intracellular pathogen Anaplasma phagocytophilum. An increase in A. phagocytophilum replication was observed in Wolbachia-infected tick cells. However, Wolbachia infection densities decreased when cells were serially passaged and ultimately the infection was lost. Host-cell immune response was also examined as an additional factor that could have affected A. phagocytophilum replication in Wolbachia-infected cells. In early passages post-Wolbachia infection, a decreased immune response was observed, but in later passages of cells with low Wolbachia densities, there was no change in the immune response. The results are discussed in relation to the importance of studying the interactions of the tick microbiota, the host cell, and the pathogen and the development of novel tick and tick-borne disease-control approaches.
First ever gene-edited ticks offer new weapons against Lyme disease
20524N. Lavars, New Atlas, 2022-02-16 08:14:12.
Gene editing in ticks had been thought to be impossible until now, and with good reason. Tick embryos are very tricky to inject because the egg that contains them has a tough layer on the outside, high pressure levels inside, and is also coated in a waxy layer the mothers create using what's called the Gené's organ."Despite their capacity to acquire and pass on an array of debilitating pathogens, research on ticks has lagged behind other arthropod vectors, such as mosquitoes, largely because of challenges in applying available genetic and molecular tools," said Monika Gulia-Nuss, a co-senior author of the study and a molecular biologist at the University of Nevada, Reno. Gulia-Nuss and her research team, which included scientists from the University of Maryland and Penn State University, believe they have finally cracked the code. The first step in the breakthrough technique involves ablating the Gené's organ to prevent the formation of the waxy coating. The eggs were then treated with chemicals benzalkonium chloride and sodium chloride to both eliminate the tough protective layer and lower the pressure inside the eggs.
A gene drive does not spread easily in populations of the honey bee parasite Varroa destructor
20173N. R. Faber, A. B. Meiborg, G. R. McFarlane, G. Gorjanc and B. A. Harpur, Apidologie, 52:1112-1127. 2022-01-25 09:13:37.
Varroa mites (Varroa destructor) are the most significant threat to beekeeping worldwide. They are directly or indirectly responsible for millions of colony losses each year. Beekeepers are somewhat able to control varroa populations through the use of physical and chemical treatments. However, these methods range in effectiveness, can harm honey bees, can be physically demanding on the beekeeper, and do not always provide complete protection from varroa. More importantly, in some populations varroa mites have developed resistance to available acaricides. Overcoming the varroa mite problem will require novel and targeted treatment options. Here, we explore the potential of gene drive technology to control varroa. We show that spreading a neutral gene drive in varroa is possible but requires specific colony-level management practices to overcome the challenges of both inbreeding and haplodiploidy. Furthermore, continued treatment with acaricides is necessary to give a gene drive time to fix in the varroa population. Unfortunately, a gene drive that impacts female or male fertility does not spread in varroa. Therefore, we suggest that the most promising way forward is to use a gene drive which carries a toxin precursor or removes acaricide resistance alleles. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13592-021-00891-5.
Cas9-Mediated Gene-Editing in the Black-Legged Tick, Ixodes Scapularis, by Embryo Injection and ReMOT Control.
17197A. a. P. Sharma, Michael N. and Reyes, Jeremiah B. and Chana, Randeep and Yim, Won C. and Heu, Chan C. and Kim, Donghun and Chaverra-Rodriguez, Duverney and Rasgon, Jason L. and Harrell, Robert A. and Nuss, Andrew B. and Gulia-Nuss, Monika,, Cell Reports, 2021-08-20 20:35:08.
Despite their capacity to acquire and pass on an array of debilitating pathogens, research on ticks has lagged behind other arthropod vectors, such as mosquitoes, largely because of a lack of genetic and molecular tools. CRISPR-Cas9 is transforming non-model organism research; however, successful gene editing has not yet been reported in ticks. Technical challenges for injecting tick embryos to attempt gene editing have further slowed research progress. Herein we report a successful tick embryo injection protocol for the black-legged tick, Ixodes scapularis, the first for any chelicerate species, and the use of this protocol for genome editing with CRISPR-Cas9. We also demonstrated for the first time that the ReMOT Control technique can be successfully used to generate genome mutations outside Insecta. Our results provide innovative tools to the tick research community that are essential for advancing our understanding of the molecular mechanisms governing pathogen transmission by tick vectors as well as for understanding the underlying biology of host-vector-pathogen interactions.
Area-Wide Integrated Management of a Glossina palpalis gambiensis Population from the Niayes Area Of Senegal: A review of operational research in support of a phased conditional approach
25657M. J. B. Vreysen, M. T. Seck, B. Sall, A. G. Mbaye, M. Bassene, A. G. Fall, M. Lo and J. Bouyer, AREA-WIDE INTEGRATED PEST MANAGEMENT:, 2021-06-12 13:45:08.
In 2005, the Government of Senegal initiated a project entitled "Projet de lutte contre les glossines dans les Niayes" (Tsetse control project in the Niayes) with the aim of creating a zone free of Glossina palpalis gambiensis in that area. The project received technical and financial support from the International Atomic Energy Agency (IAEA), the Food and Agriculture Organization of the United Nations (FAO), the Centre de Cooperation Internationale en Recherche Agronomique pour le Developpement (CIRAD) and the US Department of State through the Peaceful Uses Initiative (PUI). It was implemented in the context of the Pan African Tsetse and Trypanosomosis Eradication Campaign (PATTEC) following a phased conditional approach (PCA) that entails implementation in distinct phases, in which support to the next phase is conditional upon completion of all (or at least the majority of) activities in the previous phase. In the case of the tsetse project in Senegal, the PCA consisted of 4 phases: (1) commitment of all stakeholders and training, (2) baseline data collection, feasibility studies and strategy development, (3) preparatory pre-operational activities and (4) operational activities. This paper provides an overview of the main activities that were carried out within each phase, with emphasis on the operational research carried out in phases 2 and 3, that was instrumental in guiding the project's decision-making. Activities of phase 2 focused on the collection of entomological, veterinary, socio-economic and environmental baseline data, and a population genetics study that proved the isolated character of the G. p. gambiensis population of the Niayes. These data enabled the tsetse-infested area to be delimited to 1000 km(2), the impact of animal trypanosomosis on the farmers' welfare to be quantified (annual benefits of 2 million Euro in the tsetse-infested zone), and the formulation of an area-wide integrated pest management (AW-IPM) strategy that included a sterile insect (SIT) component to eradicate the isolated tsetse populations from the Niayes. In view of the extreme fragmentation of the remaining favourable habitat of the Niayes and the high human population density (peri-urban area), which excluded the possibility of using the Sequential Aerosol Technique, the IPM strategy that was selected comprised the suppression of the tsetse population with insecticide-impregnated traps/targets and the use of "pour-on" for cattle, followed by the release of sterile males to eliminate the remaining relic pockets. During phase 3, the pre-operational phase, a series of activities were carried out that were needed to implement the operational phase. These included the establishment of a colony of tsetse originating from the target area in Senegal, competitiveness studies between the sterile flies and those from the target area, development of transport methods for long-distance shipments of sterile male pupae, competitiveness of the sterile male flies after release in the target area, development of aerial release methods (including a new chilled adult release system) and development of a Maxent-based distribution model to guide the suppression, sterile male releases and monitoring of the eradication campaign. To be able to properly manage the eradication campaign in different phases, the entire target area was divided into 3 operational blocks. This paper demonstrates how, during the operational phase, scientific principles continued to guide the implementation process. The results to date are encouraging, i.e. the deployment of 269 insecticide-impregnated Vavoua traps in favourable habitat of Block 1 reduced the apparent density of the G. p. gambiensis population significantly (from 0.42 (SD 0.39) to 0.04 (SD 0.11) flies/trap/day). This was followed by the aerial release of sterile males that reduced the apparent density to zero after six months of releases. The last wild fly was trapped on August 9, 2012 in Block 1. In Block 2, during the suppression, the apparent fly density dropped from 1.24 (SD 1.23) to 0.005 (SD 0.017) flies/trap/day. Sterile male releases were initiated in February 2014 and expanded to cover the entire Block 2 in January 2015. The apparent fly density has so far been reduced to < 0.001 fly per trap per day until the end of 2018 and releases are still ongoing. The results of the campaign are discussed with respect to the "adaptive management approach" used, which was deemed critical for the success of the campaign.
Genetic Manipulation of Ticks: A Paradigm Shift in Tick and Tick-Borne Diseases Research
17164A. Nuss, A. Sharma and M. Gulia-Nuss, Frontiers in Cellular and Infection Microbiology, 11:7. 2021-05-02 19:18:28.
Ticks are obligate hematophagous arthropods that are distributed worldwide and are one of the most important vectors of pathogens affecting humans and animals. Despite the growing burden of tick-borne diseases, research on ticks has lagged behind other arthropod vectors, such as mosquitoes. This is largely because of challenges in applying functional genomics and genetic tools to the idiosyncrasies unique to tick biology, particularly techniques for stable genetic transformations. CRISPR-Cas9 is transforming non-model organism research; however, successful germline editing has yet to be accomplished in ticks. Here, we review the ancillary methods needed for transgenic tick development and the use of CRISPR/Cas9, the most promising gene-editing approach, for tick genetic transformation.
Meiotic drive does not cause condition-dependent reduction of the sexual ornament in stalk-eyed flies
17034S. R. Finnegan, M. Mondani, K. Fowler and A. Pomiankowski, Journal of Evolutionary Biology, 11. 2021-02-28 11:18:46.
Meiotic drive systems are associated with low-frequency chromosomal inversions. These are expected to accumulate deleterious mutations due to reduced recombination and low effective population size. We test this prediction using the 'sex-ratio' (SR) meiotic drive system of the Malaysian stalk-eyed fly Teleopsis dalmanni. SR is associated with a large inversion (or inversions) on the X chromosome. In particular, we study eyespan in males carrying the SR chromosome, as this trait is a highly exaggerated, sexually dimorphic trait, known to have heightened condition-dependent expression. Larvae were raised in low and high larval food stress environments. SR males showed reduced eyespan under the low and high stress treatments, but there was no evidence of a condition-dependent decrease in eyespan under high stress. Similar but more complex patterns were observed for female eyespan, with evidence of additivity under low stress and heterosis under high stress. These results do not support the hypothesis that reduced sexual ornament size in meiotic drive males is due to a condition-dependent response to the putative increase in mutation load. Instead, reduced eyespan likely reflects compensatory resource allocation to different traits in response to drive-mediated destruction of sperm.
Researchers help complete world first wasp genome project
14798Staff, The National Tribune, 2020-10-21 15:12:01.
In a world first, New Zealand researchers have sequenced the genome of three wasps, two of which are invasive wasps in New Zealand, paving the way for new methods of control for these significant pests.
Researchers complete world first wasp genome project
14796University of Otago, Phys Org, 2020-10-21 15:07:20.
In a world first, New Zealand researchers have sequenced the genome of three wasps, two of which are invasive wasps in New Zealand, paving the way for new methods of control for these significant pests.
Towards rangatiratanga in pest management? Maori perspectives and frameworks on novel biotechnologies in conservation
14653S. Palmer, O. R. Mercier and A. King-Hunt, Pacific Conservation Biology, 11. 2020-10-09 13:58:04.
We gathered Maori perspectives on novel biotechnological controls for pest wasps through three distinct studies. Study participants included tertiary students, businesses, and spiritual or religiously affiliated groups. All participants drew from their identities as Maori people to help identify their position on these issues.
Biotechnologies in pest wasp control: taking the sting out of pest management for Māori businesses?
14710S. Palmer and O. R. Mercier, New Genetics and Society, 2020-07-31 19:13:18.
A Maori-centered mixed-method study gauged the perceptions of eight Maori businesses about the potential use of five specific new biotechnological controls in pest management.
The potential for a CRISPR gene drive to eradicate or suppress globally invasive social wasps
13486P. J. Lester, M. Bulgarella, J. W. Baty, P. K. Dearden, J. Guhlin and J. M. Kean, Scientific Reports, 10:12398. 2020-07-24 17:41:41.
P. J. Lester, M. Bulgarella, J. W. Baty, P. K. Dearden, J. Guhlin and J. M. Kean (2020). Scientific Reports. doi: 10.1038/s41598-020-69259-6 Gene drives have potential for widespread and cost-efficient pest control, but are highly controversial. We examined a potential gene drive targeting spermatogenesis to control the invasive common wasp (Vespula vulgaris) in New Zealand.
How do you make a gene drive mosquito?
13053GeneConvene Virtual Institute, GeneConvene Global Collaborative, 2020-07-17 14:10:32.
This short video explains and illustrates how transgenic mosquitoes are made in the laboratory. While mosquitoes are the focus of the video, the process shown is used to create transgenic insects of almost any species.
A fly model establishes distinct mechanisms for synthetic CRISPR/Cas9 sex distorters
7973B. Fasulo, A. Meccariello, M. Morgan, C. Borufka, P. A. Papathanos and N. Windbichler, PLOS Genetics, 16:e1008647. 2020-03-13 15:02:19.
Author summary Harmful insect populations can be eliminated for a lack of females if they are made to produce mostly male offspring. There are genes that occur naturally that make males produce mostly sons and, although we don’t know exactly how they work, this appears to coincide with damage to the X-chromosome during the production of sperm. Recently, we showed in a mosquito species that such sex-biasing genes could also be constructed artificially from first principles. To better understand if this works in other species too, we designed and built male-biasing genes of two types in the fruit fly and determined what is needed to for a shift towards males. We show how different ways of cutting the X-chromosome DNA at different times with CRISPR, results in distinct outcomes and started to ask what cellular processes are involved in this. These models will help us to design such genes for the control of insect species that transmit disease or threaten crops.
Engineered symbionts activate honey bee immunity and limit pathogens
19387P. Leonard Sean, J. E. Powell, J. Perutka, P. Geng, C. Heckmann Luke, D. Horak Richard, W. Davies Bryan, D. Ellington Andrew, E. Barrick Jeffrey and A. Moran Nancy, Science, 367:573-576. 2020-01-31 17:14:03.
Honey bees are essential pollinators threatened by colony losses linked to the spread of parasites and pathogens. Here, we report a new approach for manipulating bee gene expression and protecting bee health. We engineered a symbiotic bee gut bacterium, Snodgrassella alvi, to induce eukaryotic RNA interference (RNAi) immune responses. We show that engineered S. alvi can stably recolonize bees and produce double-stranded RNA to activate RNAi and repress host gene expression, thereby altering bee physiology, behavior, and growth. We used this approach to improve bee survival after a viral challenge, and we show that engineered S. alvi can kill parasitic Varroa mites by triggering the mite RNAi response. This symbiont-mediated RNAi approach is a tool for studying bee functional genomics and potentially for safeguarding bee health.
Senegal celebrates first victory against tsetse fly eradication
27128FAO, FAO, 2020-01-01 13:40:22.
A campaign against the tsetse fly, a pest that transmits a disease that devastates livestock, in the Niayes area near the capital Dakar started four years ago paving the way for complete eradication of this pest. “I have not seen a single tsetse fly for a year now,” said cattle farmer Oumar Sow. “This is in contrast to earlier, when they increased in numbers, especially during the cold season. The flies were really a nuisance to our animals and we had to carefully select the time for milking. Now, there is no problem with that.” Senegal has successfully integrated an insect birth control technique using irradiation to sterilize male flies, reducing the fly population over time. The technique has already eradicated the fly population in one area in the Niayes, suppressed it in another by 98 per cent, while the technique will be implemented in a third area in 2016, said Baba Sall, Project Manager at Senegal’s Ministry of Livestock and Animal Production.
Fitness consequences of a non-recombining sex-ratio drive chromosome can explain its prevalence in the wild
5797Dyer, K. A. and D. W. Hall, Proceedings of the Royal Society B: Biological Sciences, 286:20192529. 2019-12-19 14:27:34.
Understanding the pleiotropic consequences of gene drive systems on host fitness is essential to predict their spread through a host population. Here, we study sex-ratio (SR) X-chromosome drive in the fly Drosophila recens, where SR causes the death of Y-bearing sperm in male carriers. SR males only sire daughters, which all carry SR, thus giving the chromosome a transmission advantage. The prevalence of the SR chromosome appears stable, suggesting pleiotropic costs. It was previously shown that females homozygous for SR are sterile, and here, we test for additional fitness costs of SR. We found that females heterozygous for SR have reduced fecundity and that male SR carriers have reduced fertility in conditions of sperm competition. We then use our fitness estimates to parametrize theoretical models of SR drive and show that the decrease in fecundity and sperm competition performance can account for the observed prevalence of SR in natural populations. In addition, we found that the expected equilibrium frequency of the SR chromosome is particularly sensitive to the degree of multiple mating and performance in sperm competition. Together, our data suggest that the mating system of the organism should be carefully considered during the development of gene drive systems.
A cross-sectional survey of biosafety professionals regarding genetically modified insects
5650O’Brochta, D. A., W. K. Tonui, B. Dass and S. James, Applied Biosafety, 2019:1-9. 2019-12-17 17:57:33.
Background:Genetic technologies such as gene editing and gene drive create challenges for existing frameworks used to assess risk and make regulatory determinations by governments and institutions. Insect genetic technologies including transgenics, gene editing, and gene drive may be particularly challenging because of the large and increasing number of insect species being genetically modified and the degree of familiarity with these organisms and technologies by biosafety officials charged with making containment decisions.Methods:An anonymous online survey of biosafety professionals was distributed to the membership of ABSA International, a global society of biosafety professionals, to investigate their perspectives on their preparedness to meet these new challenges.Results:Existing guidance used to make containment decisions for nongenetically modified insects was widely seen as adequate, and most respondents thought the available guidance for making containment decisions for genetically modified insects with and without gene drives was inadequate. Most respondents reported having less confidence in their decisions concerning containment of genetically modified insects compared to decisions involving genetically modified microbes, (noninsect) animals, and plants.Conclusions:These results reveal a need for additional support for biosafety professionals to improve the quality of and confidence in containment decisions regarding genetically modified insects with and without gene drive. These needs might be addressed by increasing training, updating existing guidance, creating new guidance, and creating a third-party accreditation entity to support institutions. Sixty percent of the respondents said they either would or might use a voluntary third-party accreditation service to support insect containment decisions.
The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes
5648Alcalay, Y., S. Fuchs, R. Galizi, F. Bernardini, R. E. Haghighat-Khah, D. B. Rusch, J. R. Adrion, M. W. Hahn, P. Tortosa and P. A. Papathanos, bioRxiv, 2019:860551. 2019-12-17 17:51:02.
Synthetic sex-ratio distorters based on X-chromosome shredding are predicted to be more efficient than sterile males for population suppression of malaria mosquitoes using genetic control. X chromosome shredding operates through the targeted elimination of X-chromosome-bearing gametes during male spermatogenesis, resulting in males that have a high fraction of male offspring. Strains harboring autosomal constructs containing a modified endonuclease I-PpoI have now been developed in the malaria mosquito Anopheles gambiae, resulting in strong sex-ratio distortion towards males. Data are being gathered for these strains for submission of regulatory dossiers for contained use and subsequent field release in West Africa. Since autosomal X shredders are transmitted in a Mendelian fashion and can be selected against their frequency in the population is expected to decline once releases are halted. However, any unintended transfer of the X-shredder to the Y-chromosome could theoretically change these dynamics: This could lead to 100% transmission of the newly Y-linked X-shredder to the predominant male-biased offspring and its insulation from negative selection in females, resulting in its potential spread in the population and ultimately to suppression. Here, we analyze plausible mechanisms whereby an autosomal X-shredder could become linked to the Y-chromosome after release and provide data regarding its potential for activity should it become linked to the Y-chromosome. Our results strongly suggest that Y-chromosome linkage through remobilization of the transposon used for the initial genetic transformation is unlikely, and that, in the unexpected event that the X-shredder becomes linked to the Y-chromosome, expression and activity of the X-shredder would likely be inhibited by meiotic sex chromosome inactivation. We conclude that a functioning X-shredding based Y-drive resulting from a naturally induced transposition or translocation of the transgene onto the Y-chromosome is unlikely.
Maintenance of fertility in the face of meiotic drive
5622Meade, L., S. Finnegan, R. Kad, K. Fowler and A. Pomiankowsk, The American Naturalist, 2019:2019. 2019-12-17 16:32:30.
Selfish genetic elements that gain a transmission advantage through the destruction of sperm have grave implications for drive male fertility. In the X-linked SR meiotic drive system of a stalk-eyed fly, we found that drive males have greatly enlarged testes and maintain high fertility despite the destruction of half their sperm, even when challenged with fertilizing large numbers of females. Conversely, we observed reduced allocation of resources to the accessory glands that probably explains the lower mating frequency of SR males. Body size and eyespan were also reduced, which are likely to impair viability and pre-copulatory success. We discuss the potential evolutionary causes of these differences between drive and standard males.
An assessment of the immune costs associated with meiotic drive elements in Drosophila
5614Lea, J. K. and R. L. Unckless, Proceedings of the Royal Society B: Biological Sciences, 286:20191534. 2019-12-17 16:21:00.
Most organisms are constantly adapting to pathogens and parasites that exploit their host for their own benefit. Less studied, but perhaps more ubiquitous, are intragenomic parasites or selfish genetic elements. These include transposable elements, selfish B chromosomes and meiotic drivers that promote their own replication without regard to fitness effects on hosts. Therefore, intragenomic parasites are also a constant evolutionary pressure on hosts. Gamete-killing meiotic drive elements are often associated with large chromosomal inversions that reduce recombination between the drive and wild-type chromosomes. This reduced recombination is thought to reduce the efficacy of selection on the drive chromosome and allow for the accumulation of deleterious mutations. We tested whether gamete-killing meiotic drive chromosomes were associated with reduced immune defence against two bacterial pathogens in three species of Drosophila. We found little evidence of reduced immune defence in lines with meiotic drive. One line carrying the Drosophila melanogaster autosomal Segregation Distorter did show reduced defence, but we were unable to attribute that reduced defence to either genotype or immune gene expression differences. Our results suggest that though gamete-killing meiotic drive chromosomes probably accumulate deleterious mutations, those mutations do not result in reduced capacity for immune defence.
Invasive insects: Management methods explored
5612McLaughlin, G. M. and P. K. Dearden, Journal of Insect Science, 19:1-9. 2019-12-17 16:18:09.
Invasive insect species can act as a plague across the globe, capable of vast expansion and rapid, proliferate reproduction. The spread of pathogens of serious diseases such as malaria and Zika virus and damages to agricultural crops number some of the afflictions invasive insects provide to humans alone. Additionally, an escape from predators can fail to keep invasive insects in check, providing potential threats such as extra resource competition to native species when insects invade. A variety of methods are employed to combat these invasive species, each with their own varying levels of success. Here, we explore the more traditional methods of invasive insect pest control, such as pesticides and biological control. In lieu of several unintended consequences resulting from such practices, we suggest some should be abandoned. We evaluate the potential of new techniques, in particular, those with a genetic component, regarding the costs, benefits and possible consequences of implementing them. And finally, we consider which techniques should be the focus of future research, if we truly wish to manage or even eradicate invasive insects in their introduced lands.
Identification and characterisation of a Masculinizer homolog in the diamondback moth Plutella xylostella
5607Harvey-Samuel, T., V. C. Norman, R. Carter, E. Lovett and L. Alphey, Insect Molecular Biology, 2019:2019. 2019-12-17 16:09:12.
Recently, a novel sex-determination system was identified in the silkworm (Bombyx mori) in which a piRNA encoded on the female-specific W chromosome silences a Z-linked gene (Masculinizer) which would otherwise initiate male sex-determination and dosage compensation. Masculinizer provides various opportunities for developing improved genetic pest management tools. A pest lepidopteran in which a genetic pest management system has been developed, but which would benefit greatly from such improved designs, is the diamondback moth, Plutella xylostella. However, Masculinizer has not yet been identified in this species. Here, focusing on the previously described ?masculinizing? domain of B. mori Masculinizer, we identify P. xylostella Masculinizer (PxyMasc). We show that PxyMasc is Z-linked, regulates sex-specific alternative splicing of doublesex and is necessary for male survival. Similar results in B. mori suggest this survival effect is possibly through failure to initiate male dosage compensation. The highly conserved function and location of this gene between these two distantly related lepidopterans suggests a deep role for Masculinizer in the sex-determination systems of the Lepidoptera.
A novel drug-inducible sex separation technique for insects
5605Kandul, N. P., J. Liu, A. D. Hsu, B. A. Hay and O. S. Akbari, bioRxiv, 2019:2019.12.13.875716. 2019-12-17 16:05:02.
Large sterile male releases are the gold standard for most insect population control methods and thus precise sex sorting is essential to the success of these technologies. Sex sorting is especially important for mosquito control because female mosquitoes bite and transmit diseases. However, current methods for insect sex sorting have deficiencies as they are error prone, low throughput, expensive, reduce male fitness, or lack cross species adaptability. Here we describe a novel drug-inducible system for insect sex-separation that demonstrates proof-of-principle for positive sex selection in D. melanogaster. The system exploits the toxicity of commonly used broad-spectrum antibiotics geneticin and puromycin and rescues only one sex. Sex specific rescue is achieved by inserting the sex-specific introns, TraF and DsxM, into the coding sequence of antibiotic resistance genes, NeoR or PuroR. We engineer a dual sex-sorter gene cassette and demonstrate sex specific, constitutive expression of NeoR and PuroR proteins in females and males, respectively. When raised on geneticin supplements, this sex-sorter line established 100% positive selection for female progeny, while the food supplemented with puromycin generated 100% male progeny. This system is 100% efficient and operates at remarkably low fitness costs in D. melanogaster. Since the described system exploits a conserved sex-specific splicing mechanism and reagents, which are active in many insects, it has the potential to be adaptable to insect species of medical and agricultural importance.
The bold plan to end malaria with a gene drive
5462VOX, 2019-12-13 16:52:47.
How genetically engineered mosquitoes might defeat a disease that kills millions of children. This describes gene drive and features work from a group (Target Malaria) that is developing this technology for use against malaria
Out for blood: the fight against the planet’s deadliest creature
5681Matsangou, E., The New Economy, 2019-12-02 19:16:40.
The deadliest creature on the planet is not a great white shark, a starved lion, an enraged hippopotamus or a poisonous snake – it’s the minute mosquito. According to the World Health Organisation (WHO), mosquitoes kill millions of people each year, with malaria – the most deadly mosquito-borne disease – responsible for more than half of these fatalities. The Bill and Melinda Gates Foundation has noted: “Malaria’s economic impact is estimated to cost billions of dollars in lost productivity every year.”
Evolutionary simulations of Z-linked suppression gene drives
6643L. Holman, Proceedings of the Royal Society B-Biological Sciences, 286:1-9. 2019-10-09 20:23:58.
Synthetic gene drives may soon be used to suppress or eliminate populations of disease vectors, pathogens, invasive species, and agricultural pests. Recent proposals have focused on using Z-linked gene drives to control species with ZW sex determination, which include Lepidopteran pests, parasitic trematodes, and cane toads. These proposals include Z-linked 'W-shredders', which would suppress populations by cleaving the W chromosome and causing females to produce only sons, as well as Z-linked female-sterilizing gene drives. Here, I use eco-evolutionary simulations to evaluate the potential of some proposed Z-linked gene drives, and to produce recommendations regarding their design and use. The simulations show that W-shredders are likely to be highly effective at eradicating populations provided that resistance to W-shredding cannot evolve. However, W-shredder alleles can invade populations from very low frequencies, making it difficult to eliminate specific populations while leaving nearby populations untouched; this issue may restrict their possible uses.
Assessment of a split homing based gene drive for efficient knockout of multiple genes
5915Kandul, N. P., J. Liu, A. Buchman, V. M. Gantz, E. Bier and O. S. Akbari, bioRxiv, 2019:706929. 2019-07-18 16:34:25.
Homing based gene drives (HGD) possess the potential to spread linked cargo genes into natural populations and are poised to revolutionize population control of animals. Given that host-encoded genes have been identified that are important for pathogen transmission, targeting these genes using guide RNAs as cargo genes linked to drives may provide a robust method to prevent transmission. However, effectiveness of the inclusion of additional guide RNAs that target separate host encoded genes has not been thoroughly explored. To test this approach, here we generated a split-HGD in Drosophila melanogaster that encoded a drive linked effector consisting of a second gRNA engineered to target a separate host encoded gene, which we term a gRNA-mediated effector (GME). This design enabled us to assess homing and knockout efficiencies of two target genes simultaneously, and also explore the timing and tissue specificity of Cas9 expression on cleavage/homing rates. We demonstrate that inclusion of a GME can result in high efficiency of disruption of its target gene during super-Mendelian propagation of split-HGD. However, maternal deposition and embryonic expression of Cas9 resulted in the generation of drive resistant alleles which can accumulate and limit the spread of such a drive. Alternative design principles are discussed that could mitigate the accumulation of resistance alleles while incorporating a GME.
Interpopulation spread of a parasitic B chromosome is unlikely through males in the grasshopper Eyprepocnemis plorans
6166M. I. Manrique-Poyato, J. Cabrero, M. D. López-León, F. Perfectti, R. Gómez and J. P. M. Camacho, Heredity, 124:197-206. 2019-07-08 18:29:07.
The near-neutral model of B chromosome evolution predicts that population invasion is quite fast. To test this prediction, in 1994, we introduced males of the grasshopper Eyprepocnemis plorans from a B-carrying population into a B-lacking population and monitored the evolution of B-chromosome frequency up to 2013. We observed fluctuating very low B frequency across years but, remarkably, the B chromosome introduced (the B2 variant) was found up to 1996 only, whereas the B1 variant was present from 1996 onwards, presumably introduced by fishermen using E. plorans males as bait. Effective introgression of genetic material from the donor population was evidenced by the presence of a satellite DNA on autosome 9 (up to 1999) and the presence of one individual in 2006 showing an ISSR marker profile being highly similar to that found in the donor population. This indicated that the males introduced by us effectively mated with resident females, but donor genes rapidly decreased in frequency after this non-recurrent migration event. Taken together, our results indicated: (i) that the non-recurrent migration event had a slight, transient genetic effect on the recipient population, which was diluted in only a few generations; and (ii) that even with recurrent migration (forced by fishermen) the B chromosome failed to increase in frequency. Bearing in mind that B chromosomes in this species drive through females only, we hypothesize that B chromosomes most likely failed invasion in both migration events because the migrating sex shows no B-drive.
Effective strategies for safeguarding CRISPR gene-drive experiments
4540ScienceDaily, ScienceDaily, 2019-01-22 00:00:00.
Researchers have demonstrated for the first time how two molecular strategies can safeguard CRISPR gene-drive experiments in the lab, according to a new study.
Genome-wide transcriptome profiling reveals genes associated with meiotic drive system of Aedes aegypti
3943Shin, DB, K. Susanta; Severson, W. David, Insects, 10:e25. 2019-01-21 00:00:00.
Aedes aegypti is an important mosquito vector of several arboviruses, including dengue, yellow fever, Zika, and Chikungunya, which cause significant human morbidity and mortality globally. In certain populations of this mosquito, a native meiotic drive system causes abnormal spermatogenesis that results in highly male-biased progenies from some matings. Although the basic genetics and cytogenetics of the drive mechanism were elucidated, very little is known on a transcriptome level about how the meiotic drive phenotype is expressed in individual males. To address this question, we conducted a whole-genome microarray expression study of testes from a meiotic-drive-carrying strain (T37) in comparison with testes from a non-drive-carrying strain (RED). Based on bioinformatics analyses of the microarray data, we identified 209 genes associated with the meiotic drive phenotype that were significantly differentially expressed between the two strains. K-means cluster analysis revealed nine clusters, in which genes upregulated in T37 testes were assigned to five clusters and genes downregulated in T37 testes were assigned to four clusters. Our data further revealed that genes related to protein translation, phosphorylation, and binding, as well as to G-protein-coupled receptor (GPCR) and peptidase activities, are differentially upregulated in testes from males with the meiotic drive genotype. Based on pathway analysis of these differentially expressed genes, it was observed that the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway may play a role in the meiotic drive system. Overall, this investigation enhances our understanding of whole-genome gene expression associated with the meiotic drive system in Ae. aegypti.
Killing two bugs with one stone: a perspective for targeting multiple pest species by incorporating reproductive interference into sterile insect technique
3921Honma, AK, N.; Noriyuki, S., Pest Management Science, 75:571-577. 2019-01-19 00:00:00.
The sterile insect technique is an environmentally friendly method to control and even eradicate agricultural and veterinary insect pests without using chemical pesticides in excess. However, the continuous production and release of sterile insects is economically costly and eradication programs using sterile insects have not always been successful owing to the incomplete mating ability of the sterile insects. Here we focus on the theory and empirical findings of interspecific negative mating interaction, known as reproductive interference, to develop a more cost-effective and value-added pest management program. We suggest that sterile insects can be used for simultaneous control of both wild-type conspecifics and closely related pest species by taking advantage of the fact that, when species recognition abilities are incomplete, courtship and mating are often misdirected toward heterospecies. This new approach might help mitigate economic damage and human health crises caused by pest insects. (c) 2018 Society of Chemical Industry
Arthropod containment guidelines, version 3.2
3920American Committee of Medical Entomology, American Society of Tropical Medicine and Hygiene Vector-Borne and Zoonotic Diseases, 19:3:152-173. 2019-01-18 00:00:00.
In 2003, just a few months after I became editor of Vector-; Borne and Zoonotic Diseases, we published the Arthropod; Containment Guidelines, likely our first of what would become; known as an Open Access publication. The concept to; produce the guidelines resulted from a discussion with staff; from the National Institutes of Health that had been involved; in supporting efforts to develop the capacity to genetically; engineer mosquitoes. What followed was more than a 2-year; effort by members of the American Committee for Medical; Entomology (ACME)—a subgroup of the American Society; of Tropical Medicine and Hygiene (ASTMH). Drafts of the; document were widely circulated among researchers and; vector biologists, and revised several times until a consensus; document was finalized. The guidelines were rapidly embraced; by the international community as the ‘‘go-to’’ reference; document for those working with arthropod vectors in; laboratories, and administrators on committees that oversee; these facilities.
Gene drives as a response to infection and resistance
3919Hayirli, TCM, P.F., Infection and Drug Resistance, 12:229-234. 2019-01-17 00:00:00.
Vector-borne infectious diseases continue to be a major threat to public health. Although some prevention and treatment modalities exist for these diseases, resistance to such modalities, exacerbated by global climate change, remains a fundamental challenge. Developments in genomic engineering technologies present a new front in battling vector-borne illnesses; however, there is a lack of consensus over the scope and consequences of these approaches. In this article, we use malaria as a case study to address the developments and controversies surrounding gene drives, a novel genomic engineering technology. We draw attention to the themes of infection control, resistance, and reversibility using a science and technology studies framework. Unlike other current prevention and treatment modalities, gene drives have the capacity to alter not only single organisms but also entire species and ecologies. Therefore, broader public and scientific engagement is needed to inform a more inclusive discussion between clinicians, researchers, policy makers, and society.
Efficient allelic-drive in Drosophila
3915Guichard, AH, T.; Bobik, M.; Xu, X. R. S.; Klanseck, C.; Kushwah, R. B. S.; Berni, M.; Kaduskar, B.; Gantz, V. M.; Bier, E., Nature Communications, 10:1640. 2019-01-13 00:00:00.
Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. Here, we generalize this "active genetic" approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. We test two configurations for allelic-drive: one, copy-cutting, in which a nonpreferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located in close proximity to the gRNA cut site. We also characterize a phenomenon we refer to as lethal-mosaicism that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process we refer to as "shadow-drive", have broad practical applications in improving health and agriculture and greatly extend the active genetics toolbox.
Cleave and Rescue, a novel selfish genetic element and general strategy for gene drive
3934Oberhofer, GI, T.; Hay, B. A., Proceedings of the National Academy of Sciences of the United States of America, 116:6250-6259. 2019-01-12 00:00:00.
There is great interest in being able to spread beneficial traits throughout wild populations in ways that are self-sustaining. Here, we describe a chromosomal selfish genetic element, CleaveR [Cleave and Rescue (ClvR)], able to achieve this goal. ClvR comprises two linked chromosomal components. One, germline-expressed Cas9 and guide RNAs (gRNAs)-the Cleaver-cleaves and thereby disrupts endogenous copies of a gene whose product is essential. The other, a recoded version of the essential gene resistant to cleavage and gene conversion with cleaved copies-the Rescue-provides essential gene function. ClvR enhances its transmission, and that of linked genes, by creating conditions in which progeny lacking ClvR die because they have no functional copies of the essential gene. In contrast, thosewho inherit ClvR survive, resulting in an increase in ClvR frequency. ClvR is predicted to spread to fixation under diverse conditions. To test these predictions, we generated a ClvR element in Drosophilamelanogaster. ClvRtko is located on chromosome 3 and uses Cas9 and four gRNAs to disrupt melanogaster technical knockout (tko), an X-linked essential gene. Rescue activity is provided by tko from Drosophila virilis. ClvRtko results in germline and maternal carryover-dependent inactivation of melanogaster tko (> 99% per generation); lethality caused by this loss is rescued by the virilis transgene; ClvRtko activities are robust to genetic diversity in strains from five continents; and uncleavable but functional melanogaster tko alleles were not observed. Finally, ClvRtko spreads to transgene fixation. The simplicity of ClvR suggests it may be useful for altering populations in diverse species.
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9-mediated mutagenesis of the multiple edematous wings gene induces muscle weakness and flightlessness in Bactrocera dorsalis (Diptera: Tephritidae)
3954Zheng, WL, Q.; Sun, H.; Ali, M. W.; Zhang, H., Insect Molecular Biology, 28:222-234. 2019-01-12 00:00:00.
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system is a versatile, efficient and heritable gene editing tool that can be useful for genome engineering. Bactrocera dorsalis (Hendel) is a major pest of agriculture that causes great economic losses. We used the B. dorsalis multiple edematous wings (Bdmew) gene as the target gene to explore the effectiveness of CRISPR/Cas9 for B. dorsalis genome manipulation. We studied the physiological functions of the Bdmew gene, particularly those related to muscle development. Site-specific genome editing was feasible using direct microinjection of specific guide RNA and the Cas9-plasmid into B. dorsalis embryos. Mutation frequencies ranged from 12.1 to 30.2% in the injected generation. Mosaic G0, with the mew mutation, was heritable to the next generation. The G1 displayed a series of defective phenotypes including muscle weakness, flightlessness, failure to eclose, wing folds and unbalanced movement. These results demonstrated that CRISPR/Cas9 can act as a highly specific, efficient, heritable tool for genome manipulation in B. dorsalis and this has significance for gene function research and genetic control of pests. The Bdmew gene possesses key functions in muscle development of B. dorsalis. Bdmew mutations cause a series of serious defects by interfering with muscle development and may provide a means for controlling B. dorsalis via a gene-based method such as gene drive.
Efficient somatic and germline genome engineering of Bactrocera dorsalis by the CRISPR/Cas9 system
3953Zhao, STX, Z. Z.; Liu, Z. G.; Liu, Y. H.; Liu, X. R.; Chen, Z.; Li, J. H.; Yan, R. H., Pest Management Science, 75:1921-1932. 2019-01-11 00:00:00.
Bactrocera dorsalis (Hendel), a very destructive insect pest of many fruits and vegetables, is widespread in many Asian countries. To facilitate control of this pest, it is essential to investigate its genetics and gene function using targeted gene disruption. RESULTS Here, we describe successful targeted mutagenesis of the white and transformer genes in B. dorsalis through use of the clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) system. Co-injection of the white sgRNA and Cas9 mRNA into B. dorsalis embryos caused eye color change, and the white mutations in the germline were heritable. CRISPR-mediated knockout of the sex determination gene transformer (tra) in B. dorsalis resulted in a male-biased sex ratio and adult flies with abnormal outer and interior reproductive organs. Small indels and substitutions were induced by CRIRPR for both genes. CONCLUSION Our data demonstrate that somatic and germline genome engineering of the pest B. dorsalis can be performed efficiently using the CRISPR/Cas9 system, opening the door to the use of the CRISPR-mediated method for functional annotations of genes in B. dorsalis and for its population control using, for example, such as gene drive. (c) 2018 Society of Chemical Industry
Gene drive for population genetic control: non-functional resistance and parental effects
3888Beaghton, AKH, Andrew; Nolan, Tony; Crisanti, Andrea; Burt, Austin, Proceedings of the Royal Society B: Biological Sciences, 286:20191586. 2019-01-06 00:00:00.
Gene drive is a natural process of biased inheritance that, in principle, could be used to control pest and vector populations. As with any form of pest control, attention should be paid to the possibility of resistance evolving. For nuclease-based gene drive aimed at suppressing a population, resistance could arise by changes in the target sequence that maintain function, and various strategies have been proposed to reduce the likelihood that such alleles arise. Even if these strategies are successful, it is almost inevitable that alleles will arise at the target site that are resistant to the drive but do not restore function, and the impact of such sequences on the dynamics of control has been little studied. We use population genetic modelling of a strategy targeting a female fertility gene to demonstrate that such alleles may be expected to accumulate, and thereby reduce the reproductive load on the population, if nuclease expression per se causes substantial heterozygote fitness effects or if parental (especially paternal) deposition of nuclease either reduces offspring fitness or affects the genotype of their germline. All these phenomena have been observed in synthetic drive constructs. It will, therefore, be important to allow for non-functional resistance alleles in predicting the dynamics of constructs in cage populations and the impacts of any field release.
Gene driving the farm: who decides, who owns, and who benefits?
3907Montenegro de Wit, M, Agroecology and Sustainable Food Systems, 43:1054-1074. 2019-01-05 00:00:00.
This commentary essay explores the social and ecological implications of gene-driving agriculture.
Targeting female reproduction in insects with biorational insecticides for pest management: a critical review with suggestions for future research
3946Smagghe, GZ, M.; Retnakaran, A., Current Opinion in Insect Science, 31:65-69. 2019-01-04 00:00:00.
Of the different approaches to pest control, use of juvenile hormone analogs (e.g. methoprene), molting hormone (20-hydroxyecdysone) analogs (e.g. tebufenozide) and chitin synthesis inhibitors (e.g. diflubenzuron) has dominated this field. Since they adversely interfere with the normal growth and development in one way or another, they have been collectively called as 'insect growth regulators' or IGRs. A lesser known fact is that they all have deleterious effects on reproduction as well as act as ovicides. The raison d'etre for this review is to summarize what we have learnt during the last 3-4 decades in the use of these IGRs, how they affect insect reproduction and how we can apply this knowledge to control pest insects. Finally, we present, information on the state of the art use of molecular technologies such as RNAi and CRISPR/Cas9 applications for pest management targeting insect reproduction.
A Framework for the risk assessment and management of gene drive technology in contained use
4023van der Vlugt, CJBB, David D.; Lehmann, Kathleen; Leunda, Amaya; Willemarck, Nicolas, Applied Biosafety, 23:25-31. 2018-01-21 00:00:00.
The utilisation of the CRISPR/Cas9 technology has sparked a renewed interest in gene drive mechanisms. These mechanisms of biased inheritance may yield promising applications in the fields of vector control and nature conservation. However, the same properties that will enable these applications may also pose a risk if organisms that are equipped with gene drive cassettes are unintentionally released into the environment. Although several groups of scientists and regulators have started to address these safety concerns, there are currently no dedicated guidelines published on the required risk assessment and minimal control measures applicable to gene drive organisms in contained use. To fill this gap, this paper describes a fundamental approach to assessing the risks of these organisms while handled in a contained laboratory environment. Based on the likelihood that an adverse effect will arise from the handling of a gene drive organism and the severity of this effect, three risk classes for contained use activities are presented. Finally, specific minimum requirements regarding physical measures and working practices are proposed according to the presented risk classes and tailored to activities with rodents, insects, and fungi, which are most likely to be used for gene drive applications in the near future.
Gene drive to reduce malaria transmission in sub-Saharan Africa
3963Burt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K., Journal of Responsible Innovation, 5:S66-S80. 2018-01-21 00:00:00.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of mosquitoes and/or reduce vector competence. As with any control measure, due attention should be paid to the possible evolution of resistance. No gene drive construct has yet been reported that is "field-ready" for release, and when such constructs are developed, they should be assessed on a case-by-case basis. Gene drive approaches to vector control promise to have a number of key features that motivate their continued development, and scrutiny, by all concerned.
Pathway to deployment of gene drive mosquitoes as a potential biocontrol tool for elimination of malaria in sub-Saharan Africa: Recommendations of a scientific working group
3982James, SC, Frank H.; Welkhoff, Philip A.; Emerson, Claudia; Godfray, H. Charles J.; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W.; Mbogo, Charles M.; Okumu, Fredros O.; Quemada, Hector; Savadogo, Moussa; Singh, Jerome A.; Tountas, Karen H.; Touré, American Journal of Tropical Medicine and Hygiene, 98:1-49. 2018-01-20 00:00:00.
Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes, focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes.
Synthetically engineered Medea gene drive system in the worldwide crop pest Drosophila suzukii
3962Buchman, AM, John M.; Ostrovski, Dennis; Yang, Ting; Akbari, Omar S., Proceedings of the National Academy of Sciences of the United States of America, 115:4725-4730. 2018-01-20 00:00:00.
Here we describe a fully functional gene drive system constructed in a major worldwide crop pest, Drosophila suzukii. This system is composed of a synthetic Medea drive with a maternal miRNA “toxin” and a zygotic “antidote,” and we demonstrate that it can bias inheritance with 100% efficiency and can persist in a population given high release frequencies. We discuss how such a system may be used to suppress D. suzukii populations or render them harmless to target crops.Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of a synthetic Medea gene drive system in a major worldwide crop pest, Drosophila suzukii. We demonstrate that this drive system, based on an engineered maternal “toxin” coupled with a linked embryonic “antidote,” is capable of biasing Mendelian inheritance rates with up to 100% efficiency. However, we find that drive resistance, resulting from naturally occurring genetic variation and associated fitness costs, can be selected for and hinder the spread of such a drive. Despite this, our results suggest that this gene drive could maintain itself at high frequencies in a wild population and spread to fixation if either its fitness costs or toxin resistance were reduced, providing a clear path forward for developing future such systems in this pest.
Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in Drosophila
3961Buchman, ABI, Tobin; Marshall, John M.; Akbari, Omar S.; Hay, Bruce A., ACS Synthetic Biology, 7:1359-1370. 2018-01-19 00:00:00.
Replacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions using gene drive provides a self-perpetuating method of disease prevention. Mechanisms that require the gene drive element and linked cargo to exceed a high threshold frequency in order for spread to occur are attractive because they offer several points of control: they bring about local, but not global population replacement; and transgenes can be eliminated by reintroducing wildtypes into the population so as to drive the frequency of transgenes below the threshold frequency required for drive. Reciprocal chromosome translocations were proposed as a tool for bringing about high threshold population replacement in 1940 and 1968. However, translocations able to achieve this goal have only been reported once, in the spider mite Tetranychus urticae, a haplo-diploid species in which there is strong selection in haploid males for fit homozygotes. We report the creation of engineered translocation-bearing strains of Drosophila melanogaster, generated through targeted chromosomal breakage and homologous recombination. These strains drive high threshold population replacement in laboratory populations. While it remains to be shown that engineered translocations can bring about population replacement in wild populations, these observations suggest that further exploration of engineered translocations as a tool for controlled population replacement is warranted.
Rapid comeback of males: evolution of male-killer suppression in a green lacewing population
3979Hayashi, MN, M.; Kageyama, D., Proceedings of the Royal Society B-Biological Sciences, 285:6. 2018-01-17 00:00:00.
Evolutionary theory predicts that the spread of cytoplasmic sex ratio distorters leads to the evolution of host nuclear suppressors, although there are extremely few empirical observations of this phenomenon. Here, we demonstrate that a nuclear suppressor of a cytoplasmic male killer has spread rapidly in a population of the green lacewing Mallada desjardinsi. An M. desjardinsi population, which was strongly female-biased in 2011 because of a high prevalence of the male-killing Spiroplasma endosymbiont, had a sex ratio near parity in 2016, despite a consistent Spiroplasma prevalence. Most of the offspring derived from individuals collected in 2016 had 1 : 1 sex ratios in subsequent generations. Contrastingly, all-female or female-biased broods appeared frequently from crossings of these female offspring with males derived from a laboratory line founded by individuals collected in 2011. These results suggest near-fixation of a nuclear suppressor against male killing in 2016 and reject the notion that a non-male-killing Spiroplasma variant has spread in the population. Consistently, no significant difference was detected in mitochondrial haplotype variation between 2011 and 2016. These findings, and earlier findings in the butterfly Hypolimnas bolina in Samoa, suggest that these quick events of male recovery occur more commonly than is generally appreciated.
Origin, composition, and structure of the supernumerary B chromosome of Drosophila melanogaster
3978Hanlon, SLM, Danny E.; Eche, Salam; Hawley, R. Scott, Genetics, 210:1197. 2018-01-16 00:00:00.
The number of chromosomes carried by an individual species is one of its defining characteristics. Some species, however, can also carry supernumerary chromosomes referred to as B chromosomes. B chromosomes were recently identified in a laboratory stock of Drosophila melanogaster—an established model organism with a wealth of genetic and genomic resources—enabling us to subject them to extensive molecular analysis. We isolated the B chromosomes by pulsed-field gel electrophoresis and determined their composition through next-generation sequencing. Although these B chromosomes carry no known euchromatic sequence, they are rich in transposable elements and long arrays of short nucleotide repeats, the most abundant being the uncharacterized AAGAT satellite repeat. Fluorescent in situ hybridization on metaphase chromosome spreads revealed this repeat is located on chromosome 4, strongly suggesting the origin of the B chromosomes is chromosome 4. Cytological and quantitative comparisons of signal intensity between chromosome 4 and the B chromosomes supports the hypothesis that the structure of the B chromosome is an isochromosome. We also report the identification of a new B chromosome variant in a related laboratory stock. This B chromosome has a similar repeat signature as the original but is smaller and much less prevalent. We examined additional stocks with similar genotypes and did not find B chromosomes, but did find these stocks lacked the AAGAT satellite repeat. Our molecular characterization of D. melanogaster B chromosomes is the first step toward understanding how supernumerary chromosomes arise from essential chromosomes and what may be necessary for their stable inheritance.
Improved CRISPR-based suppression gene drives mitigate resistance and impose a large reproductive load on laboratory-contained mosquito populations
3977Hammond, AMK, Kyros; Gribble, Matthew; Karlsson, Xenia; Morianou, Ioanna; Galizi, Roberto; Beaghton, Andrea; Crisanti, Andrea; Nolan, Tony, bioRxiv, 360339:1-16. 2018-01-15 00:00:00.
CRISPR-based genes drives bias their own inheritance and can be used to modify entire populations of insect vectors of disease as a novel form of sustainable disease control. Gene drives designed to interfere with female fertility can suppress populations of the mosquito vector of malaria, however laboratory demonstrations showed strong unintended fitness costs and high levels of resistant mutations that limited the potential of the first generation of gene drives to spread. We describe three new gene drives designed to restrict spatio-temporal nuclease expression by using novel regulatory sequences. Two of the three new designs dramatically improve fitness and mitigate the creation and selection of resistance. We dissect the relative contributions of germline CRISPR activity versus embryonic CRISPR activity resulting from parental deposition, showing that the improved performance of the new designs is due to tighter germline restriction of the nuclease activity and significantly lower rates of end-joining repair in the embryo. Moreover, we demonstrate in laboratory-contained population experiments that these gene drives show remarkably improved invasion dynamics compared to the first generation drives, resulting in greater than 90% suppression of the reproductive output and a delay in the emergence of target site resistance, even at a loosely constrained target sequence. These results illustrate important considerations for gene drive design and will help expedite the development of gene drives designed to control malaria transmission in Africa.
Genetics and genomics of an unusual selfish sex ratio distortion in an insect
3976Hamilton, PTH, C. N.; Curtis, C. I.; Perlman, S. J., Current Biology, 28:3864-3870. 2018-01-14 00:00:00.
Diverse selfish genetic elements have evolved the ability to manipulate reproduction to increase their transmission, and this can result in highly distorted sex ratios [1]. Indeed, one of the major explanations for why sex determination systems are so dynamic is because they are shaped by ongoing coevolutionary arms races between sex-ratio-distorting elements and the rest of the genome [2]. Here, we use genetic crosses and genome analysis to describe an unusual sex ratio distortion with striking consequences on genome organization in a booklouse species, Liposcelis sp. (Insecta: Psocodea), in which two types of females coexist. Distorter females never produce sons but must mate with males (the sons of nondistorting females) to reproduce [3]. Although they are diploid and express the genes inherited from their fathers in somatic tissues, distorter females only ever transmit genes inherited from their mothers. As a result, distorter females have unusual chimeric genomes, with distorter-restricted chromosomes diverging from their nondistorting counterparts and exhibiting features of a giant non-recombining sex chromosome. The distorter-restricted genome has also acquired a gene from the bacterium Wolbachia, a well-known insect reproductive manipulator; we found that this gene has independently colonized the genomes of two other insect species with unusual reproductive systems, suggesting possible roles in sex ratio distortion in this remarkable genetic system.
Satellite DNAs unveil clues about the ancestry and composition of B chromosomes in three grasshopper species
3995Milani, DB, Vanessa; Ferretti, Ana; Palacios-Gimenez, Octavio; Melo, Adriana; Moura, Rita; Loreto, Vilma; Song, Hojun; Cabral-de-Mello, Diogo, Genes, 9:e523. 2018-01-13 00:00:00.
Supernumerary (B) chromosomes are dispensable genomic elements occurring frequently among grasshoppers. Most B chromosomes are enriched with repetitive DNAs, including satellite DNAs (satDNAs) that could be implicated in their evolution. Although studied in some species, the specific ancestry of B chromosomes is difficult to ascertain and it was determined in only a few examples. Here we used bioinformatics and cytogenetics to characterize the composition and putative ancestry of B chromosomes in three grasshopper species, Rhammatocerus brasiliensis, Schistocerca rubiginosa, and Xyleus discoideus angulatus. Using the RepeatExplorer pipeline we searched for the most abundant satDNAs in Illumina sequenced reads, and then we generated probes used in fluorescent in situ hybridization (FISH) to determine chromosomal position. We used this information to infer ancestry and the events that likely occurred at the origin of B chromosomes. We found twelve, nine, and eighteen satDNA families in the genomes of R. brasiliensis, S. rubiginosa, and X. d. angulatus, respectively. Some satDNAs revealed clustered organization on A and B chromosomes varying in number of sites and position along chromosomes. We did not find specific satDNA occurring in the B chromosome. The satDNAs shared among A and B chromosomes support the idea of putative intraspecific ancestry from small autosomes in the three species, i.e., pair S11 in R. brasiliensis, pair S9 in S. rubiginosa, and pair S10 in X. d. angulatus. The possibility of involvement of other chromosomal pairs in B chromosome origin is also hypothesized. Finally, we discussed particular aspects in composition, origin, and evolution of the B chromosome for each species.
Gene flow mediates the role of sex chromosome meiotic drive during complex speciation
3994Meiklejohn, CDL, Emily L.; Gordon, Kathleen E.; Rzatkiewicz, Thomas; Kingan, Sarah B.; Geneva, Anthony J.; Vedanayagam, Jeffrey P.; Muirhead, Christina A.; Garrigan, Daniel; Stern, David L.; Presgraves, Daven C., eLife, 7:e35468. 2018-01-12 00:00:00.
During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build-up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, we combine high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow between the fruitfly species, Drosophila mauritiana and D. simulans. Our findings reveal a high density of genetic incompatibilities and a corresponding dearth of gene flow on the X chromosome. Surprisingly, we find that a known drive element recently migrated between species and, rather than contributing to interspecific divergence, caused a strong reduction in local sequence divergence, undermining the evolution of hybrid sterility. Gene flow can therefore mediate the effects of selfish genetic elements during speciation.
CRISPR-based gene drives for pest control
3992McFarlane, GRW, C. Bruce A.; Lillico, Simon G., Trends in Biotechnology, 36:130-133. 2018-01-10 00:00:00.
Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene drives (GDs) could be used to spread desirable genetic elements through wild populations. With the imminent development of this technology in vertebrates, we believe that it is timely to highlight two forms of sex-ratio distorting GDs that show potential as pest management tools.
Unexpected patterns of segregation distortion at a selfish supergene in the fire ant Solenopsis invicta
4010Ross, KGS, DeWayne, BMC Genetics, 19:101. 2018-01-08 00:00:00.
The Sb supergene in the fire ant Solenopsis invicta determines the form of colony social organization, with colonies whose inhabitants bear the element containing multiple reproductive queens and colonies lacking it containing only a single queen. Several features of this supergene — including suppressed recombination, presence of deleterious mutations, association with a large centromere, and “green-beard” behavior — suggest that it may be a selfish genetic element that engages in transmission ratio distortion (TRD), defined as significant departures in progeny allele frequencies from Mendelian inheritance ratios. We tested this possibility by surveying segregation ratios in embryo progenies of 101 queens of the “polygyne” social form (3512 embryos) using three supergene-linked markers and twelve markers outside the supergene.
Reducing resistance allele formation in CRISPR gene drive
3968Champer, JL, Jingxian; Oh, Suh Yeon; Reeves, Riona; Luthra, Anisha; Oakes, Nathan; Clark, Andrew G.; Messer, Philipp W., Proceedings of the National Academy of Sciences of the United States of America, 115:5522-5527. 2018-01-06 00:00:00.
A functioning gene drive mechanism could fundamentally change our strategies for the control of vector-borne diseases, such as malaria, dengue, and Zika. CRISPR homing gene drive promises such a mechanism, which could be used to rapidly spread genetic modifications among the mosquitoes that transmit these diseases. However, recent studies have shown that current drives would likely be unable to spread in insect populations due to the high rate at which resistance will evolve. In this study, we provide an experimental demonstration that guide RNA multiplexing can successfully reduce resistance rates but also find that such an approach would still need to be combined with additional strategies to create drives that are efficient enough for use in wild populations.CRISPR homing gene drives can convert heterozygous cells with one copy of the drive allele into homozygotes, thereby enabling super-Mendelian inheritance. Such a mechanism could be used, for example, to rapidly disseminate a genetic payload in a population, promising effective strategies for the control of vector-borne diseases. However, all CRISPR homing gene drives studied in insects thus far have produced significant quantities of resistance alleles that would limit their spread. In this study, we provide an experimental demonstration that multiplexing of guide RNAs can both significantly increase the drive conversion efficiency and reduce germline resistance rates of a CRISPR homing gene drive in Drosophila melanogaster. We further show that an autosomal drive can achieve drive conversion in the male germline, with no subsequent formation of resistance alleles in embryos through paternal carryover of Cas9. Finally, we find that the nanos promoter significantly lowers somatic Cas9 expression compared with the vasa promoter, suggesting that nanos provides a superior choice in drive strategies where gene disruption in somatic cells could have fitness costs. Comparison of drive parameters among the different constructs developed in this study and a previous study suggests that, while drive conversion and germline resistance rates are similar between different genomic targets, embryo resistance rates can vary significantly. Taken together, our results mark an important step toward developing effective gene drives capable of functioning in natural populations and provide several possible avenues for further control of resistance rates.
A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes
3987Kyrou, KH, Andrew M.; Galizi, Roberto; Kranjc, Nace; Burt, Austin; Beaghton, Andrea K.; Nolan, Tony; Crisanti, Andrea, Nature Biotechnology, 36:1062–1066. 2018-01-05 00:00:00.
In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) whose sequence is highly conserved in all Anopheles mosquitoes so far analyzed. We found that CRISPR–Cas9-targeted disruption of the intron 4–exon 5 boundary aimed at blocking the formation of functional AgdsxF did not affect male development or fertility, whereas females homozygous for the disrupted allele showed an intersex phenotype and complete sterility. A CRISPR–Cas9 gene drive construct targeting this same sequence spread rapidly in caged mosquitoes, reaching 100% prevalence within 7–11 generations while progressively reducing egg production to the point of total population collapse. Owing to functional constraint of the target sequence, no selection of alleles resistant to the gene drive occurred in these laboratory experiments. Cas9-resistant variants arose in each generation at the target site but did not block the spread of the drive.
Redkmer: An assembly-free pipeline for the identification of abundant and specific X-chromosome target sequences for X-shredding by CRISPR endonucleases
4006Papathanos, PAW, Nikolai, CRISPR Journal, 1:88-98. 2018-01-04 00:00:00.
CRISPR-based synthetic sex ratio distorters, which operate by shredding the X-chromosome during male meiosis, are promising tools for the area-wide control of harmful insect pest or disease vector species. X-shredders have been proposed as tools to suppress insect populations by biasing the sex ratio of the wild population toward males, thus reducing its natural reproductive potential. However, to build synthetic X-shredders based on CRISPR, the selection of gRNA targets, in the form of high-copy sequence repeats on the X chromosome of a given species, is difficult, since such repeats are not accurately resolved in genome assemblies and cannot be assigned to chromosomes with confidence. We have therefore developed the redkmer computational pipeline, designed to identify short and highly abundant sequence elements occurring uniquely on the X chromosome. Redkmer was designed to use as input minimally processed whole genome sequence data from males and females. We tested redkmer with short- and long-read whole genome sequence data of Anopheles gambiae, the major vector of human malaria, in which the X-shredding paradigm was originally developed. Redkmer established long reads as chromosomal proxies with excellent correlation to the genome assembly and used them to rank X-candidate kmers for their level of X-specificity and abundance. Among these, a high-confidence set of 25-mers was identified, many belonging to previously known X-chromosome repeats of Anopheles gambiae,including the ribosomal gene array and the selfish elements harbored within it. Data from a control strain, in which these repeats are shared with the Y chromosome, confirmed the elimination of these kmers during filtering. Finally, we show that redkmer output can be linked directly to gRNA selection and off-target prediction. In addition, the output of redkmer, including the prediction of chromosomal origin of single-molecule long reads and chromosome specific kmers, could also be used for the characterization of other biologically relevant sex chromosome sequences, a task that is frequently hampered by the repetitiveness of sex chromosome sequence content.
Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs
4005Oberhofer, GI, Tobin; Hay, Bruce A., Proceedings of the National Academy of Sciences of the United States of America, 115:e9343. 2018-01-03 00:00:00.
Homing endonuclease gene (HEG)-based gene drive can bring about population suppression when genes required for viability or fertility are targeted. However, these strategies are vulnerable to failure through mechanisms that create alleles resistant to cleavage but that retain wild-type gene function. We show that resistance allele creation can be prevented through the use of guide RNAs designed to cleave a gene at four target sites. However, homing rates were modest, and the HEGs were unstable during homing. In addition, use of a promoter active in the female germline resulted in levels of HEG carryover that compromised the viability or fertility of HEG-bearing heterozygotes, thereby preventing drive. We propose strategies that can help to overcome these problems in next-generation HEG systems.A gene drive method of particular interest for population suppression utilizes homing endonuclease genes (HEGs), wherein a site-specific, nuclease-encoding cassette is copied, in the germline, into a target gene whose loss of function results in loss of viability or fertility in homozygous, but not heterozygous, progeny. Earlier work in Drosophila and mosquitoes utilized HEGs consisting of Cas9 and a single guide RNA (gRNA) that together target a specific gene for cleavage. Homing was observed, but resistant alleles immune to cleavage, while retaining wild-type gene function, were also created through nonhomologous end joining. Such alleles prevent drive and population suppression. Targeting a gene for cleavage at multiple positions has been suggested as a strategy to prevent the appearance of resistant alleles. To test this hypothesis, we generated two suppression HEGs in Drosophila melanogaster targeting genes required for embryonic viability or fertility, using a HEG consisting of CRISPR/Cas9 and gRNAs designed to cleave each gene at four positions. Rates of target locus cleavage were very high, and multiplexing of gRNAs prevented resistant allele formation. However, germline homing rates were modest, and the HEG cassette was unstable during homing events, resulting in frequent partial copying of HEGs that lacked gRNAs, a dominant marker gene, or Cas9. Finally, in drive experiments, the HEGs failed to spread due to the high fitness load induced in offspring as a result of maternal carryover of Cas9/gRNA complex activity. Alternative design principles are proposed that may mitigate these problems in future gene drive engineering.
Consequences of resistance evolution in a Cas9-based sex conversion-suppression gene drive for insect pest management
3985Carrami, Eli M., ME, Kolja N.; Ahmed, Hassan M. M.; Sánchez C., Héctor M.; Dippel, Stefan; Marshall, John M.; Wimmer, Ernst A., Proceedings of the National Academy of Sciences of the United States of America, 115:6189-6194. 2018-01-03 00:00:00.
Resistance evolution caused by CRISPR/Cas9 gene-drive systems has a major impact on both the future scientific design of such gene-drive systems and on the politics of regulating experimentation and use of such systems. In our study, we show that in-frame drive-resistant alleles can be produced readily and inherently in a suppression gene-drive system. The rate at which such alleles emerge will determine the maximum size of the population that could be targeted for collapse and elimination. Here, we provide a potential target site and the modeling framework for implementation and optimization of a suppression gene-drive strategy to control Mediterranean fruit fly populations.The use of a site-specific homing-based gene drive for insect pest control has long been discussed, but the easy design of such systems has become possible only with the recent establishment of CRISPR/Cas9 technology. In this respect, novel targets for insect pest management are provided by new discoveries regarding sex determination. Here, we present a model for a suppression gene drive designed to cause an all-male population collapse in an agricultural pest insect. To evaluate the molecular details of such a sex conversion-based suppression gene drive experimentally, we implemented this strategy in Drosophila melanogaster to serve as a safe model organism. We generated a Cas9-based homing gene-drive element targeting the transformer gene and showed its high efficiency for sex conversion from females to males. However, nonhomologous end joining increased the rate of mutagenesis at the target site, which resulted in the emergence of drive-resistant alleles and therefore curbed the gene drive. This confirms previous studies that simple homing CRISPR/Cas9 gene-drive designs will be ineffective. Nevertheless, by performing population dynamics simulations using the parameters we obtained in D. melanogaster and by adjusting the model for the agricultural pest Ceratitis capitata, we were able to identify adequate modifications that could be successfully applied for the management of wild Mediterranean fruit fly populations using our proposed sex conversion-based suppression gene-drive strategy.
Strong hybrid male incompatibilities impede the spread of a selfish chromosome between populations of a fly
4024Verspoor Rudi, LSJ, M. L.; Mannion Natasha, L. M.; Hurst Gregory, D. D.; Price Tom, A. R., Evolution Letters, 2:169-179. 2018-01-02 00:00:00.
Meiotically driving sex chromosomes manipulate gametogenesis to increase their transmission at a cost to the rest of the genome. The intragenomic conflicts they produce have major impacts on the ecology and evolution of their host species. However, their ecological dynamics remain poorly understood. Simple population genetic models predict meiotic drivers will rapidly reach fixation in populations and spread across landscapes. In contrast, natural populations commonly show spatial variation in the frequency of drivers, with drive present in clines or mosaics across species ranges. For example, Drosophila subobscura harbors a sex ratio distorting drive chromosome (SRs) at 15?25% frequency in North Africa, present at less than 2% frequency in adjacent southern Spain, and absent in other European populations. Here, we investigate the forces preventing the spread of the driver northward. We show that SRs has remained at a constant frequency in North Africa, and failed to spread in Spain. We find strong evidence that spread is impeded by genetic incompatibility between SRs and Spanish autosomal backgrounds. When we cross SRs from North Africa onto Spanish genetic backgrounds we observe strong incompatibilities specific to hybrids bearing SRs. The incompatibilities increase in severity in F2 male hybrids, leading to almost complete infertility. We find no evidence supporting an alternative hypothesis, that there is resistance to drive in Spanish populations. We conclude that the source of the stepped frequency variation is genetic incompatibility between the SRs chromosome and the genetic backgrounds of the adjacent population, preventing SRs spreading northward. The low frequency of SRs in South Spain is consistent with recurrent gene flow across the Strait of Gibraltar combined with selection against the SRs element through genetic incompatibility. This demonstrates that incompatibilities between drive chromosomes and naïve populations can prevent the spread of drive between populations, at a continental scale.
The IAEA and Food – Tsetse Fly Eradication – Senegal
25659International Atomic Energy Agency, IAEA/FAO, 2017-06-21 14:02:20.
Senegal has successfully integrated the Sterile Insect Technique into its tsetse fly control project in the Niayes region. This nuclear technique suppresses or even eradicates insect pest by using radiation to sterilize primarily males. The disease that tsetse flies transmit can kill livestock or make them sick.
Gene Drive for Mosquito Control: Where Did It Come from and Where Are We Headed?
4055Macias, VMO, J. R.; Rasgon, J. L., International Journal of Environmental Research and Public Health, 14:e1006. 2017-01-13 00:00:00.
Mosquito-borne pathogens place an enormous burden on human health. The existing toolkit is insufficient to support ongoing vector-control efforts towards meeting disease elimination and eradication goals. The perspective that genetic approaches can potentially add a significant set of tools toward mosquito control is not new, but the recent improvements in site-specific gene editing with CRISPR/Cas9 systems have enhanced our ability to both study mosquito biology using reverse genetics and produce genetics-based tools. Cas9-mediated gene-editing is an efficient and adaptable platform for gene drive strategies, which have advantages over innundative release strategies for introgressing desirable suppression and pathogen-blocking genotypes into wild mosquito populations; until recently, an effective gene drive has been largely out of reach. Many considerations will inform the effective use of new genetic tools, including gene drives. Here we review the lengthy history of genetic advances in mosquito biology and discuss both the impact of efficient site-specific gene editing on vector biology and the resulting potential to deploy new genetic tools for the abatement of mosquito-borne disease.
Introduction of a male-harming mitochondrial haplotype via ‘Trojan Females’ achieves population suppression in fruit flies
4074Wolff, JNG, N. J.; Tompkins, D. M.; Dowling, D. K., eLife, 6:e23551. 2017-01-12 00:00:00.
Pests are a global threat to biodiversity, ecosystem function, and human health. Pest control approaches are thus numerous, but their implementation costly, damaging to non-target species, and ineffective at low population densities. The Trojan Female Technique (TFT) is a prospective self-perpetuating control technique that is species-specific and predicted to be effective at low densities. The goal of the TFT is to harness naturally occurring mutations in the mitochondrial genome that impair male fertility while having no effect on females. Here, we provide proof-of-concept for the TFT, by showing that introduction of a male fertility-impairing mtDNA haplotype into replicated populations of Drosophila melanogaster causes numerical population suppression, with the magnitude of effect positively correlated with its frequency at trial inception. Further development of the TFT could lead to establishing a control strategy that overcomes limitations of conventional approaches, with broad applicability to invertebrate and vertebrate species, to control environmental and economic pests.
Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations
4034Champer, JR, Riona; Oh, Suh Yeon; Liu, Chen; Liu, Jingxian; Clark, Andrew G.; Messer, Philipp W., PLOS Genetics, 13:e1006796. 2017-01-12 00:00:00.
Author summary Gene drive systems provide a wide array of potential applications, including new strategies for the control of vector-borne diseases. For example, a functioning gene drive system could rapidly spread a genetically modified allele designed to reduce pathogen transmission throughout a vector population. The recently developed CRISPR/Cas9-based gene drive mechanism works by converting wild type alleles to drive alleles in heterozygotes via cleavage and homology-directed repair. However, resistance alleles that are unable to be converted to drive alleles can also be generated during this process, which may pose a major obstacle to the practical use of such gene drives. In our study, we developed two CRISPR/Cas9 gene drive constructs using different promoters and target sites in the model organism Drosophila melanogaster. We observed that these constructs produced resistance alleles at high rates both in the germline and post-fertilization in the embryo. Additionally, conversion efficiency and resistance allele formation rates varied substantially among genetically diverse fly lines. Overall, we conclude that new gene drive approaches will be necessary to reduce the formation of resistance alleles, particularly in genetically diverse natural populations.
A pooled sequencing approach identifies a candidate meiotic driver in Drosophila
4072Wei, KHCR, H. M.; Rathnam, C.; Lee, J.; Lin, D. A. N.; Ji, S. Q.; Mason, J. M.; Clark, A. G.; Barbash, D. A., Genetics, 206:451-465. 2017-01-10 00:00:00.
Meiotic drive occurs when a selfish element increases its transmission frequency above the Mendelian ratio by hijacking the asymmetric divisions of female meiosis. Meiotic drive causes genomic conflict and potentially has a major impact on genome evolution, but only a few drive loci of large effect have been described. New methods to reliably detect meiotic drive are therefore needed, particularly for discovering moderate-strength drivers that are likely to be more prevalent in natural populations than strong drivers. Here, we report an efficient method that uses sequencing of large pools of backcross (BC1) progeny to test for deviations from Mendelian segregation genome-wide with single-nucleotide polymorphisms (SNPs) that distinguish the parental strains. We show that meiotic drive can be detected by a characteristic pattern of decay in distortion of SNP frequencies, caused by recombination unlinking the driver from distal loci. We further show that control crosses allow allele-frequency distortion caused by meiotic drive to be distinguished from distortion resulting from developmental effects. We used this approach to test whether chromosomes with extreme telomere-length differences segregate at Mendelian ratios, as telomeric regions are a potential hotspot for meiotic drive due to their roles in meiotic segregation and multiple observations of high rates of telomere sequence evolution. Using four different pairings of long and short telomere strains, we find no evidence that extreme telomere-length variation causes meiotic drive in Drosophila. However, we identify one candidate meiotic driver in a centromere-linked region that shows an similar to 8% increase in transmission frequency, corresponding to a similar to 54: 46 segregation ratio. Our results show that candidate meiotic drivers of moderate strength can be readily detected and localized in pools of BC1 progeny.
X chromosome drive in a widespread Palearctic woodland fly, Drosophila testacea
4052Keais, GLH, M. A.; Gowen, B. E.; Perlman, S. J., Journal of Evolutionary Biology, 30:1185-1194. 2017-01-10 00:00:00.
Selfish genes that bias their own transmission during meiosis can spread rapidly in populations, even if they contribute negatively to the fitness of their host. Driving X chromosomes provide a clear example of this type of selfish propagation. These chromosomes have important evolutionary and ecological consequences, and can be found in a broad range of taxa including plants, mammals and insects. Here, we report a new case of X chromosome drive (X drive) in a widespread woodland fly, Drosophila testacea. We show that males carrying the driving X (SR males) sire 80-100% female offspring and possess a diagnostic X chromosome haplotype that is perfectly associated with the sex ratio distortion phenotype. We find that the majority of sons produced by SR males are sterile and appear to lack a Y chromosome, suggesting that meiotic defects involving the Y chromosome may underlie X drive in this species. Abnormalities in sperm cysts of SR males reflect that some spermatids are failing to develop properly, confirming that drive is acting during gametogenesis. By screening wild-caught flies using progeny sex ratios and a diagnostic marker, we demonstrate that the driving X is present in wild populations at a frequency of similar to 10% and that suppressors of drive are segregating in the same population. The testacea species group appears to be a hot spot for X drive, and D. testacea is a promising model to compare driving X chromosomes in closely related species, some of which may even be younger than the chromosomes themselves.
Requirements for Driving Antipathogen Effector Genes into Populations of Disease Vectors by Homing
4031Beaghton, AH, Andrew; Nolan, Tony; Crisanti, Andrea; Godfray, H. Charles J.; Burt, Austin, Genetics, 205:1587-1596. 2017-01-09 00:00:00.
There is a need for new interventions against the ongoing burden of vector-borne diseases such as malaria and dengue. One suggestion has been to develop genes encoding effector molecules that block parasite development within the vector, and then use the nuclease-based homing reaction as a form of gene drive to spread those genes through target populations. If the effector gene reduces the fitness of the mosquito and does not contribute to the drive, then loss-of-function mutations in the effector will eventually replace functional copies, but protection may nonetheless persist sufficiently long to provide a public health benefit. Here, we present a quantitative model allowing one to predict the duration of protection as a function of the probabilities of different molecular processes during the homing reaction, various fitness effects, and the efficacy of the effector in blocking transmission. Factors that increase the duration of protection include reducing the frequency of pre-existing resistant alleles, the probability of nonrecombinational DNA repair, the probability of homing-associated loss of the effector, the fitness costs of the nuclease and effector, and the completeness of parasite blocking. For target species that extend over an area much larger than the typical dispersal distance, the duration of protection is expected to be highest at the release site, and decrease away from there, eventually falling to zero, as effector-less drive constructs replace effector-containing ones. We also model an alternative strategy of using the nuclease to target an essential gene, and then linking the effector to a sequence that restores the essential function and is resistant to the nuclease. Depending upon parameter values, this approach can prolong the duration of protection. Our models highlight the key design criteria needed to achieve a desired level of public health benefit.%U http://www.genetics.org/content/genetics/205/4/1587.full.pdf
Eradicating Mosquitoes? The promise and peril of gene drive technologies.
4050Jun, B-O, Eubios Journal of Asian and International Bioethics, 27:113-116. 2017-01-08 00:00:00.
This paper discusses the ethical issues associated with genetic modification of mosquito species that are human disease vectors. The Oxitec genetically changed mosquito—a variant of a species called Aedes aegypti, OX513A, is taken as an example. The benefits and risks are discussed, and questions need to be discussed in public prior to release of this gene drive system
Vector control with driving Y chromosomes: modelling the evolution of resistance
4030Beaghton, AB, P. J.; Burt, A., Malaria Journal, 16:286. 2017-01-08 00:00:00.
: The introduction of new malaria control interventions has often led to the evolution of resistance, both of the parasite to new drugs and of the mosquito vector to new insecticides, compromising the efficacy of the interventions. Recent progress in molecular and population biology raises the possibility of new genetic-based interventions, and the potential for resistance to evolve against these should be considered. Here, population modelling is used to determine the main factors affecting the likelihood that resistance will evolve against a synthetic, nuclease-based driving Y chromosome that produces a male-biased sex ratio. Methods: A combination of deterministic differential equation models and stochastic analyses involving branching processes and Gillespie simulations is utilized to assess the probability that resistance evolves against a driving Y that otherwise is strong enough to eliminate the target population. The model considers resistance due to changes at the target site such that they are no longer cleaved by the nuclease, and due to trans-acting autosomal suppressor alleles. Results: The probability that resistance evolves increases with the mutation rate and the intrinsic rate of increase of the population, and decreases with the strength of drive and any pleiotropic fitness costs of the resistant allele. In seasonally varying environments, the time of release can also affect the probability of resistance evolving. Trans-acting suppressor alleles are more likely to suffer stochastic loss at low frequencies than target site resistant alleles. Conclusions: As with any other intervention, there is a risk that resistance will evolve to new genetic approaches to vector control, and steps should be taken to minimize this probability. Two design features that should help in this regard are to reduce the rate at which resistant mutations arise, and to target sequences such that if they do arise, they impose a significant fitness cost on the mosquito.
Results from the Workshop “Problem Formulation for the Use of Gene Drive in Mosquitoes”
4066Roberts, ADA, P. P.; Okumu, F.; Quemada, H.; Savadogo, M.; Singh, J. A.; James, S., American Journal of Tropical Medicine and Hygiene, 96:530-533. 2017-01-04 00:00:00.
Reducing the incidence of malaria has been a public health priority for nearly a century. New technologies and associated vector control strategies play an important role in the prospect of sustained reductions. The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene-drive constructs to reduce or alter vector populations to reduce malaria incidence. However, before these technologies can be developed and exploited, it will be necessary to understand and assess the likelihood of any potential harms to humans or the environment. To begin this process, the Foundation for the National Institutes of Health and the International Life Sciences Institute Research Foundation organized an expert workshop to consider the potential risks related to the use of gene drives in Anopheles gambiae for malaria control in Africa. The resulting discussion yielded a series of consensus points that are reported here.
The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito
4046Hammond, AMK, Kyros; Bruttini, Marco; North, Ace; Galizi, Roberto; Karlsson, Xenia; Kranjc, Nace; Carpi, Francesco M.; D’Aurizio, Romina; Crisanti, Andrea; Nolan, Tony, PLOS Genetics, 13:e1007039. 2017-01-04 00:00:00.
Gene drives are selfish genetic elements that are able to bias their own inheritance among offspring. Starting from very low frequencies they can rapidly invade a population in just a few generations, even when imposing a fitness cost. Gene drives based on the precise DNA cutting enzyme CRISPR have been shown recently to be highly efficient at copying themselves from one chromosome to the other during the process of gamete formation in mosquitoes, resulting in transmission to 99% of offspring instead of the 50% expected for a single gene copy. One proposed use for CRISPR-based gene drives is in the control of mosquitoes by designing the gene drive to target mosquito genes involved in fertility, thereby reducing their overall reproductive output and leading to population suppression. Like any intervention designed to suppress a population these gene drives are expected to select for mutations in the mosquito that are resistant to the drive and restore fertility to mosquitoes. We have analyzed the origin and selection of resistant alleles in caged populations of mosquitoes initiated with a gene drive construct targeting a female fertility gene. We find the selected alleles are in-frame insertions and deletions that are resistant to cleavage and restore female fertility. Our findings allow us to improve predictions on gene drive behaviour and to make concrete recommendations on how to improve future gene drive designs by decreasing the likelihood that they generate resistance.
Driving out malaria
4598Nolan, TC, A., Scientist, 2017-01-01 00:00:00.
In recent years, researchers have sequenced the genomes of several Anopheles mosquito species, including those responsible for nearly all of the malaria transmission in Africa. With this information, they have begun to identify the genes underlying the insects’ ability to colonize human habitats, their reproductive biology, and their susceptibility to infection by the malaria parasite (Plasmodium spp.). If we know the genes, or variants of genes, that are responsible for key mosquito traits, such as parasite clearance or egg laying, we can theoretically introduce a genetic modification into the insects that reduces malaria transmission.
Prospects and challenges of CRISPR/Cas genome editing for the study and control of neglected vector-borne nematode diseases
6017M. Zamanian and E. C. Andersen, The FEBS Journal, 283:3204-3221. 2016-06-14 20:22:18.
Neglected tropical diseases caused by parasitic nematodes inflict an immense health and socioeconomic burden throughout much of the developing world. Current estimates indicate that more than two billion people are infected with nematodes, resulting in the loss of 14 million disability-adjusted life years per annum. Although these parasites cause significant mortality, they primarily cause chronic morbidity through a wide range of severe clinical ailments. Treatment options for nematode infections are restricted to a small number of anthelmintic drugs, and the rapid expansion of anthelmintic mass drug administration raises concerns of drug resistance. Preservation of existing drugs is necessary, as well as the development of new treatment options and methods of control. We focus this review on how the democratization of CRISPR/Cas9 genome editing technology can be enlisted to improve our understanding of the biology of nematode parasites and our ability to treat the infections they cause. We will first explore how this robust method of genome manipulation can be used to newly exploit the powerful model nematode Caenorhabditis elegans for parasitology research. We will then discuss potential avenues to develop CRISPR/Cas9 editing protocols in filarial nematodes. Lastly, we will propose potential ways in which CRISPR/Cas9 can be used to engineer gene drives that target the transmission of mosquito-borne filarial nematodes.
Cheating evolution: engineering gene drives to manipulate the fate of wild populations
4083Champer, JB, A.; Akbari, O. S., Nature Reviews Genetics, 17:146-159. 2016-01-21 00:00:00.
Engineered gene drives - the process of stimulating the biased inheritance of specific genes - have the potential to enable the spread of desirable genes throughout wild populations or to suppress harmful species, and may be particularly useful for the control of vector-borne diseases such as malaria. Although several types of selfish genetic elements exist in nature, few have been successfully engineered in the laboratory thus far. With the discovery of RNA-guided CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated 9) nucleases, which can be utilized to create, streamline and improve synthetic gene drives, this is rapidly changing. Here, we discuss the different types of engineered gene drives and their potential applications, as well as current policies regarding the safety and regulation of gene drives for the manipulation of wild populations.
Gene drive through a landscape: Reaction-diffusion models of population suppression and elimination by a sex ratio distorter
4081Beaghton, AB, P. J.; Burt, A., Theoretical Population Biology, 108:51-69. 2016-01-19 00:00:00.
Some genes or gene complexes are transmitted from parents to offsprihg at a greater-than-Mendelian rate, and can spread and persist in populations even if they cause some harm to the individuals carrying them. Such genes may be useful for controlling populations or species that are harmful. Driving-Y chromosomes may be particularly potent in this regard, as they produce a male-biased sex ratio that, if sufficiently extreme, can lead to population elimination. To better understand the potential of such genes to spread over a landscape, we have developed a series of reaction-diffusion models of a driving-Y chromosome in 1-D and radially-symmetric 2-D unbounded domains. The wild-type system at carrying capacity is found to be unstable to the introduction of driving-Y males for all models investigated. Numerical solutions exhibit travelling wave pulses and fronts, and analytical and semi-analytical solutions for the asymptotic wave speed under bounded initial conditions are derived. The driving-Y male invades the wild-type equilibrium state at the front of the wave and completely replaces the wild-type males, leaving behind, at the tail of the wave, a reduced- or zero-population state of females and driving-Y males only. In our simplest model of a population with one life stage and density-dependent mortality, wave speed depends on the strength of drive and the diffusion rate of Y-drive males, and is independent of the population dynamic consequences (suppression or elimination). Incorporating an immobile juvenile stage of fixed duration into the model reduces wave speed approximately in proportion to the relative time spent as a juvenile. If females mate just once in their life, storing sperm for subsequent reproduction, then wave speed depends on the movement of mated females as well as Y-drive males, and may be faster or slower than in the multiple-mating model, depending on the relative duration of juvenile and adult life stages. Numerical solutions are shown for parameter values that may in part be representative for Anopheles gambiae, the primary vector of malaria in sub-Saharan Africa. (C) 2015 The Authors. Published by Elsevier Inc.
Driven to extinction? The ethics of eradicating mosquitoes with gene-drive technologies
4097Pugh, J, Journal of Medical Ethics, 42:578-581. 2016-01-15 00:00:00.
Mosquito-borne diseases represent a significant global disease burden, and recent outbreaks of such diseases have led to calls to reduce mosquito populations. Furthermore, advances in gene-drive' technology have raised the prospect of eradicating certain species of mosquito via genetic modification. This technology has attracted a great deal of media attention, and the idea of using gene-drive technology to eradicate mosquitoes has been met with criticism in the public domain. In this paper, I shall dispel two moral objections that have been raised in the public domain against the use of gene-drive technologies to eradicate mosquitoes. The first objection invokes the concept of the sanctity of life' in order to claim that we should not drive an animal to extinction. In response, I follow Peter Singer in raising doubts about general appeals to the sanctity of life, and argue that neither individual mosquitoes nor mosquitoes species considered holistically are appropriately described as bearing a significant degree of moral status. The second objection claims that seeking to eradicate mosquitoes amounts to displaying unacceptable degrees of hubris. Although I argue that this objection also fails, I conclude by claiming that it raises the important point that we need to acquire more empirical data about, inter alia, the likely effects of mosquito eradication on the ecosystem, and the likelihood of gene-drive technology successfully eradicating the intended mosquito species, in order to adequately inform our moral analysis of gene-drive technologies in this context.
Occasional recombination of a selfish X-chromosome may permit its persistence at high frequencies in the wild
4096Pieper, KED, K. A., Journal of Evolutionary Biology, 29:2229-2241. 2016-01-14 00:00:00.
The sex-ratio X-chromosome (SR) is a selfish chromosome that promotes its own transmission to the next generation by destroying Y-bearing sperm in the testes of carrier males. In some natural populations of the fly Drosophila neotestacea, up to 30% of the X-chromosomes are SR chromosomes. To investigate the molecular evolutionary history and consequences of SR, we sequenced SR and standard (ST) males at 11 X-linked loci that span the ST X-chromosome and at seven arbitrarily chosen autosomal loci from a sample of D. neotestacea males from throughout the species range. We found that the evolutionary relationship between ST and SR varies among individual markers, but genetic differentiation between SR and ST is chromosome-wide and likely due to large chromosomal inversions that suppress recombination. However, SR does not consist of a single multilocus haplotype: we find evidence for gene flow between ST and SR at every locus assayed. Furthermore, we do not find long-distance linkage disequilibrium within SR chromosomes, suggesting that recombination occurs in females homozygous for SR. Finally, polymorphism on SR is reduced compared to that on ST, and loci displaying signatures of selection on ST do not show similar patterns on SR. Thus, even if selection is less effective on SR, our results suggest that gene flow with ST and recombination between SR chromosomes may prevent the accumulation of deleterious mutations and allow its long-term persistence at relatively high frequencies.
Gene silencing and gene drive in dengue vector control
4095Paulraj, MGI, S.; Reegan, A. D., Indian Journal of Natural Products and Resources, 7:193-200. 2016-01-13 00:00:00.
Vector-borne diseases are the most feared diseases throughout the world. Mosquitoes are the prime human disease vectors as they are responsible for nearly one million human deaths every year. So they are declared as the most dangerous insects to mankind. Aedes aegypti and Ae. albopictus are the most significant mosquito species, because of their role in transmitting dengue virus. These blood feeding ectoparasites of man and other vertebrates have developed excellent adaptations to survive and multiply in and around human habitations. Chemical-based mosquito control method does not give good results due to rapid development of pesticide resistance in mosquitoes. The past four decades have witnessed the development of several alternate mosquito control methods. Genetic control technologies have been recently developed as efficient and ecofriendly methods. Inundate release of genetically modified mosquitoes with lethal or pathogen-resistant genes for population reduction is a recent technology in mosquito control programme. Recent developments in molecular and genome editing technologies have made it easy to produce thousands of transgenic mosquitoes for field release. The present review highlights various scientific reports and research findings on gene silencing and gene drive techniques in dengue mosquito control.
Mechanisms of sex determination and transmission ratio distortion in Aedes aegypti
4089Hoang, KPT, T. M.; Ho, T. X.; Le, V. S., Parasites & Vectors, 9:49. 2016-01-07 00:00:00.
: More effective mosquito control strategies are urgently required due to the increasing prevalence of insecticide resistance. The sterile insect technique (SIT) and the release of insects carrying a dominant lethal allele (RIDL) are two proposed methods for environmentally-friendly, species-targeted population control. These methods may be more suitable for developing countries if producers reduce the cost of rearing insects. The cost of control programs could be reduced by producing all-male mosquito populations to circumvent the isolation of females before release without reducing male mating competitiveness caused by transgenes. Results: An RNAi construct targeting the RNA recognition motif of the Aedes aegypti transformer-2 (tra-2) gene does not trigger female-to-male sex conversion as commonly observed among dipterous insects. Instead, homozygous insects show greater mortality among m-chromosome-bearing sperm and mm zygotes, yielding up to 100 % males in the subsequent generations. The performance of transgenic males was not significantly different to wild-type males in narrow-cage competitive mating experiments. Conclusion: Our data provide preliminary evidence that the knockdown of Ae. aegypti tra-2 gene expression causes segregation distortion acting at the level of gametic function, which is reinforced by sex-specific zygotic lethality. This finding could promote the development of new synthetic sex distorter systems for the production of genetic sexing mosquito strains.
Rapid evolution of a Y-chromosome heterochromatin protein underlies sex chromosome meiotic drive
4088Helleu, QG, P. R.; Dubruille, R.; Ogereau, D.; Prud'homme, B.; Loppin, B.; Montchamp-Moreau, C., Proceedings of the National Academy of Sciences of the United States of America, 113:4110-4115. 2016-01-06 00:00:00.
Sex chromosome meiotic drive, the non-Mendelian transmission of sex chromosomes, is the expression of an intragenomic conflict that can have extreme evolutionary consequences. However, the molecular bases of such conflicts remain poorly understood. Here, we show that a young and rapidly evolving X-linked heterochromatin protein 1 (HP1) gene, HP1D2, plays a key role in the classical Paris sex-ratio (SR) meiotic drive occurring in Drosophila simulans. Driver HP1D2 alleles prevent the segregation of the Y chromatids during meiosis II, causing female-biased sex ratio in progeny. HP1D2 accumulates on the heterochromatic Y chromosome in male germ cells, strongly suggesting that it controls the segregation of sister chromatids through heterochromatin modification. We show that Paris SR drive is a consequence of dysfunctional HP1D2 alleles that fail to prepare the Y chromosome for meiosis, thus providing evidence that the rapid evolution of genes controlling the heterochromatin structure can be a significant source of intragenomic conflicts.
A CRISPR-Cas9 gene drive system-targeting female reproduction in the malaria mosquito vector Anopheles gambiae
4087Hammond, AG, R.; Kyrou, K.; Simoni, A.; Siniscalchi, C.; Katsanos, D.; Gribble, M.; Baker, D.; Marois, E.; Russell, S.; Burt, A.; Windbichler, N.; Crisanti, A.; Nolan, T., Nature Biotechnology, 34:78-83. 2016-01-05 00:00:00.
Gene drive systems that enable super-Mendelian inheritance of a transgene have the potential to modify insect populations over a timeframe of a few years. We describe CRISPR-Cas9 endonuclease constructs that function as gene drive systems in Anopheles gambiae, the main vector for malaria. We identified three genes (AGAP005958, AGAP011377 and AGAP007280) that confer a recessive female-sterility phenotype upon disruption, and inserted into each locus CRISPR-Cas9 gene drive constructs designed to target and edit each gene. For each targeted locus we observed a strong gene drive at the molecular level, with transmission rates to progeny of 91.4 to 99.6%. Population modeling and cage experiments indicate that a CRISPR-Cas9 construct targeting one of these loci, AGAP007280, meets the minimum requirement for a gene drive targeting female reproduction in an insect population. These findings could expedite the development of gene drives to suppress mosquito populations to levels that do not support malaria transmission.
The dawn of active genetics
4085Gantz, VMB, E., Bioessays, 38:50-63. 2016-01-03 00:00:00.
On December 18, 2014, a yellow female fly quietly emerged from her pupal case. What made her unique was that she had only one parent carrying a mutant allele of this classic recessive locus. Then, one generation later, after mating with a wild-type male, all her offspring displayed the same recessive yellow phenotype. Further analysis of other such yellow females revealed that the construct causing the mutation was converting the opposing chromosome with 95% efficiency. These simple results, seen also in mosquitoes and yeast, open the door to a new era of genetics wherein the laws of traditional Mendelian inheritance can be bypassed for a broad variety of purposes. Here, we consider the implications of this fundamentally new form of active genetics, its applications for gene drives, reversal and amplification strategies, its potential for contributing to cell and gene therapy strategies, and ethical/biosafety considerations associated with such active genetic elements.
Double trouble: combined action of meiotic drive and Wolbachia feminization in Eurema butterflies
4119Kern, PC, J. M.; Kageyama, D.; Riegler, M., Biology Letters, 11:20150095. 2015-01-17 00:00:00.
Arthropod sex ratios can be manipulated by a diverse range of selfish genetic elements, including maternally inherited Wolbachia bacteria. Feminization by Wolbachia is rare but has been described for Eurema mandarina butterflies. In this species, some phenotypic and functional females, thought to be ZZ genetic males, are infected with a feminizing Wolbachia strain, wFem. Meanwhile, heterogametic WZ females are not infected with wFem. Here, we establish a quantitative PCR assay allowing reliable sexing in three Eurema species. Against expectation, all E. mandarina females, including wFem females, had only one Z chromosome that was paternally inherited. Observation of somatic interphase nuclei confirmed that W chromatin was absent in wFem females, but present in females without wFem. We conclude that the sex bias in wFem lines is due to meiotic drive (MD) that excludes the maternal Z and thus prevents formation of ZZ males. Furthermore, wFem lines may have lost the W chromosome or harbour a dysfunctional version, yet rely on wFem for female development; removal of wFem results in all-male offspring. This is the first study that demonstrates an interaction between MD and Wolbachia feminization, and it highlights endosymbionts as potentially confounding factors in MD of sex chromosomes.
Sex chromosome drive
4117Helleu, QG, P. R.; Montchamp-Moreau, C., Cold Spring Harbor Perspectives in Biology, 7:a017616. 2015-01-15 00:00:00.
Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are over represented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species.
Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi
4115Gantz, VMJ, N.; Tatarenkova, O.; Fazekas, A.; Macias, V. M.; Bier, E.; James, A. A., Proceedings of the National Academy of Sciences of the United States of America, 112:e6736-e6743. 2015-01-13 00:00:00.
Genetic engineering technologies can be used both to create transgenic mosquitoes carrying antipathogen effector genes targeting human malaria parasites and to generate gene-drive systems capable of introgressing the genes throughout wild vector populations. We developed a highly effective autonomous Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9)-mediated gene-drive system in the Asian malaria vector Anopheles stephensi, adapted from the mutagenic chain reaction (MCR). This specific system results in progeny of males and females derived from transgenic males exhibiting a high frequency of germ-line gene conversion consistent with homology-directed repair (HDR). This system copies an similar to 17-kb construct from its site of insertion to its homologous chromosome in a faithful, site-specific manner. Dual anti-Plasmodium falciparum effector genes, a marker gene, and the autonomous gene-drive components are introgressed into similar to 99.5% of the progeny following outcrosses of transgenic lines to wild-type mosquitoes. The effector genes remain transcriptionally inducible upon blood feeding. In contrast to the efficient conversion in individuals expressing Cas9 only in the germ line, males and females derived from transgenic females, which are expected to have drive component molecules in the egg, produce progeny with a high frequency of mutations in the targeted genome sequence, resulting in near-Mendelian inheritance ratios of the transgene. Such mutant alleles result presumably from non-homologous end-joining (NHEJ) events before the segregation of somatic and germ-line lineages early in development. These data support the design of this system to be active strictly within the germ line. Strains based on this technology could sustain control and elimination as part of the malaria eradication agenda.
The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations
4114V. M. Gantz and E. Bier, Science, 348:442. 2015-01-12 00:00:00.
Loss-of-function mutations may only produce a mutant phenotype when both copies of the gene are mutated. Gantz and Bier developed a method they call mutagenic chain reaction (MCR) that autocatalytically produces homozygous mutations. MCR uses the initial mutated allele to cause a mutation in the allele on the opposing chromosome and thus the homozygosity of the trait. MCR technology could have broad applications in diverse organisms.Science, this issue p. 442 An organism with a single recessive loss-of-function allele will typically have a wild-type phenotype, whereas individuals homozygous for two copies of the allele will display a mutant phenotype. We have developed a method called the mutagenic chain reaction (MCR), which is based on the CRISPR/Cas9 genome-editing system for generating autocatalytic mutations, to produce homozygous loss-of-function mutations. In Drosophila, we found that MCR mutations efficiently spread from their chromosome of origin to the homologous chromosome, thereby converting heterozygous mutations to homozygosity in the vast majority of somatic and germline cells. MCR technology should have broad applications in diverse organisms.
Origin, evolution, and population genetics of the selfish Segregation Distorter gene duplication in European and African populations of Drosophila melanogaster
4108Brand, CLL, A. M.; Presgraves, D. C., Evolution, 69:1271-1283. 2015-01-06 00:00:00.
Meiotic drive elements are a special class of evolutionarily selfish genes that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruit fly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene Ran-GTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1-5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations.
Sex-ratio meiotic drive and Y-linked resistance in Drosophila affinis
4128Unckless, RLL, A. M.; Clark, A. G., Genetics, 199:831-840. 2015-01-06 00:00:00.
Genetic elements that cheat Mendelian segregation by biasing transmission in their favor gain a significant fitness benefit. Several examples of sex-ratio meiotic drive, where one sex chromosome biases its own transmission at the cost of the opposite sex chromosome, exist in animals and plants. While the distorting sex chromosome gains a significant advantage by biasing sex ratio, the autosomes, and especially the opposite sex chromosome, experience strong selection to resist this transmission bias. In most wellstudied sex-ratio meiotic drive systems, autosomal and/or Y-linked resistance has been identified. We specifically surveyed for Y-linked resistance to sex-ratio meiotic drive in Drosophila affinis by scoring the sex ratio of offspring sired by males with a driving X and one of several Y chromosomes. Two distinct types of resistance were identified: a restoration to 50/50 sex ratios and a complete reversal of sex ratio to all sons. We confirmed that fathers siring all sons lacked a Y chromosome, consistent with previously published work. Considerable variation in Y-chromosome morphology exists in D. affinis, but we showed that morphology does not appear to be associated with resistance to sex-ratio meiotic drive. We then used two X chromosomes (driving and standard) and three Y chromosomes (susceptible, resistant, and lacking) to examine fertility effects of all possible combinations. We find that both the driving X and resistant and lacking Y have significant fertility defects manifested in microscopic examination of testes and a 48-hr sperm depletion assay. Maintenance of variation in this sex-ratio meiotic drive system, including both the X-linked distorter and the Y-resistant effects, appear to be mediated by a complex interaction between fertility fitness and transmission dynamics.
A synthetic sex ratio distortion system for the control of the human malaria mosquito
4140Galizi, RD, L. A.; Menichelli, M.; Bernardini, F.; Deredec, A.; Burt, A.; Stoddard, B. L.; Windbichler, N.; Crisanti, A., Nature Communications, 5:3977. 2014-01-18 00:00:00.
It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action of naturally occurring sex distorters and the prevalence of co-evolving suppressors has hampered their use for control. Here we generate a synthetic sex distortion system by exploiting the specificity of the homing endonuclease I-PpoI, which is able to selectively cleave ribosomal gene sequences of the malaria vector Anopheles gambiae that are located exclusively on the mosquito's X chromosome. We combine structure-based protein engineering and molecular genetics to restrict the activity of the potentially toxic endonuclease to spermatogenesis. Shredding of the paternal X chromosome prevents it from being transmitted to the next generation, resulting in fully fertile mosquito strains that produce >95% male offspring. We demonstrate that distorter male mosquitoes can efficiently suppress caged wild-type mosquito populations, providing the foundation for a new class of genetic vector control strategies.
Biased transmission of sex chromosomes in the aphid Myzus persicae is not associated with reproductive mode
4160Wilson, ACCD, R. N.; Vorburger, C., PLOS One, 9:1-12. 2014-01-18 00:00:00.
Commonly, a single aphid species exhibits a wide range of reproductive strategies including cyclical parthenogenesis and obligate parthenogenesis. Sex determination in aphids is chromosomal; females have two X chromosomes, while males have one. X chromosome elimination at male production is generally random, resulting in equal representation of both X chromosomes in sons. However, two studies have demonstrated deviations from randomness in some lineages. One hypothesis to account for such deviations is that recessive deleterious mutations accumulate during bouts of asexual reproduction and affect male viability, resulting in overrepresentation of males with the least deleterious of the two maternal X chromosomes. This hypothesis results in a testable prediction: X chromosome transmission bias will increase with time spent in the asexual phase and should therefore be most extreme in the least sexual aphid life cycle class. Here we test this prediction in Myzus persicae. We used multiple heterozygous X-linked microsatellite markers to screen 1085 males from 95 lines of known life cycle. We found significant deviations from equal representation of X chromosomes in 15 lines; however, these lines included representatives of all life cycles. Our results are inconsistent with the hypothesis that deviations from randomness are attributable to mutation accumulation.
Male eyespan size is associated with meiotic drive in wild stalk-eyed flies (Teleopsis dalmanni)
4138Cotton, AJF, M.; Cotton, S.; Pomiankowski, A., Heredity, 112:363-369. 2014-01-16 00:00:00.
This study provides the first direct evidence from wild populations of stalk-eyed flies to support the hypothesis that male eyespan is a signal of meiotic drive. Several stalk-eyed fly species are known to exhibit X-linked meiotic drive. A recent quantitative trait locus analysis in Teleopsis dalmanni found a potential link between variation in male eyespan, a sexually selected ornamental trait, and the presence of meiotic drive. This was based on laboratory populations subject to artificial selection for male eyespan. In this study, we examined the association between microsatellite markers and levels of sex ratio bias (meiotic drive) in 12 wild T. dalmanni populations. We collected two data sets: (a) brood sex ratios of wild-caught males mated to standard laboratory females and (b) variation in a range of phenotypic traits associated with reproductive success of wild-caught males and females. In each case, we typed individuals for eight X-linked microsatellite markers, including several that previously were shown to be associated with male eyespan and meiotic drive. We found that one microsatellite marker was very strongly associated with meiotic drive, whereas a second showed a weaker association. We also found that, using both independent data sets, meiotic drive was strongly associated with male eyespan, with smaller eyespan males being associated with more female-biased broods. These results suggest that mate preference for exaggerated male eyespan allows females to avoid mating with males carrying the meiotic drive gene and is thus a potential mechanism for the maintenance and evolution of female mate preference.
A selfish gene chastened: Tribolium castaneum Medea M (4) is silenced by a complementary gene
4157Thomson, MS, Genetica, 142:161-167. 2014-01-15 00:00:00.
Maternal-effect dominant embryonic arrest (Medea) of Tribolium castaneum are autosomal factors that act maternally to cause the death of any progeny that do not inherit them. This selfish behavior is thought to result from a maternally expressed poison and zygotically expressed antidote. Medea factors and the hybrid incompatibility factor, H, have a negative interaction consistent with complementary genes of the Dobzhansky-Muller model for post-zygotic isolation. This negative interaction may result from H suppression of Medea zygotic antidote, leaving zygotes incompletely protected from maternal poison. I report here a test of the hypothesis that H also suppresses the Medea maternal poison. Viable F-1 females were generated from a cross of Medea M (4) strain males to H strain females. These females, heterozygous for both M (4) and H, failed to express M (4) maternal lethal activity when crossed to their male sibs. Transmission of non-M (4) homologues from these females was confirmed using a dominant transgenic enhanced green fluorescent protein eye color marker, tightly linked in cis to M (4) . M (4) beetles, lacking H, were selected from the F-2 population. Female descendants of these clearly expressed M (4) maternal lethal activity, indicating restoration of this activity after H was segregated away. I conclude that H, or a factor tightly linked to H, suppresses Medea M (4) maternal poison.
Heritable strategies for controlling insect vectors of disease
4136Burt, A, Philosophical Transactions of the Royal Society B-Biological Sciences, 369:20130432. 2014-01-14 00:00:00.
Mosquito-borne diseases are causing a substantial burden of mortality, morbidity and economic loss in many parts of the world, despite current control efforts, and new complementary approaches to controlling these diseases are needed. One promising class of new interventions under development involves the heritable modification of the mosquito by insertion of novel genes into the nucleus or of Wolbachia endosymbionts into the cytoplasm. Once released into a target population, these modifications can act to reduce one or more components of the mosquito population's vectorial capacity (e. g. the number of female mosquitoes, their longevity or their ability to support development and transmission of the pathogen). Some of the modifications under development are designed to be self-limiting, in that they will tend to disappear over time in the absence of recurrent releases (and hence are similar to the sterile insect technique, SIT), whereas other modifications are designed to be self-sustaining, spreading through populations even after releases stop (and hence are similar to traditional biological control). Several successful field trials have now been performed with Aedes mosquitoes, and such trials are helping to define the appropriate developmental pathway for this new class of intervention.
Meiotic drive impacts expression and evolution of X-linked genes in stalk-eyed flies
4155Reinhardt, JAB, C. L.; Paczolt, K. A.; Johns, P. M.; Baker, R. H.; Wilkinson, G. S., PLOS Genetics, 10:e1004362. 2014-01-13 00:00:00.
Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (X-SR) or a standard X chromosome (X-ST), and found hundreds of these, the majority of which are X-linked. Drive-associated transcripts show increased levels of sequence divergence (dN/dS) compared to a control set, and are predominantly expressed either in testes or in the gonads of both sexes. Finally, we confirmed that X-SR and X-ST are highly divergent by estimating sequence differentiation between the RNAseq pools. We found that X-linked transcripts were often strongly differentiated (whereas most autosomal transcripts were not), supporting the presence of a relatively large region of recombination suppression on X-SR presumably caused by one or more inversions. We have identified a group of genes that are good candidates for further study into the causes and consequences of sex-chromosome drive, and demonstrated that meiotic drive has had a profound effect on sequence evolution and gene expression of X-linked genes in this species.
Regulatory experience and challenges for the release of GM insects
4135Beech, C, Journal Fur Verbraucherschutz Und Lebensmittelsicherheit-Journal of Consumer Protection and Food Safety, 9:S71-S76. 2014-01-13 00:00:00.
Genetically modified (GM) insects are a potentially valuable new tool for the biological control of insect pests of humans, animals and plants. Considerable progress has been made recently in transfer of GM insects from the laboratory to release and evaluation in the environment. As with other new genetic technologies, regulatory agencies have often found it challenging to determine the regulatory regime under which they should be evaluated, and have either adapted existing regulatory frameworks or adopted new ones. No country has legislation specifically for GM insects. However, irrespective of the regulatory regime under which they are evaluated, the purpose of their regulation remains the same; to protect human health and the environment. Consequently there are evaluation themes common to their regulatory scrutiny, which are elucidated here. There have also been some challenges and issues encountered during the risk evaluation for field release of GM insects, and this paper will highlight some of these to assist others when considering policy, regulation and assessment of GM insects. Useful regulatory and policy precedents also exist from the regulation of biological control agents and the global protection of plants from pests under the International Standards for Phytosanitary Measures (ISPM) framework. Where countries do not have existing regulations, these evaluation instruments could have the potential to be adapted to form a suitable framework for the assessment of risk for GM insects. Finally, some considerations for future policy and regulation in this area are discussed.
Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila: A theoretical exploration of Medea-dependent population suppression
4134Akbari, OSC, C. H.; Marshall, J. M.; Huang, H. X.; Antoshechkin, I.; Hay, B. A., ACS Synthetic Biology, 3:915-928. 2014-01-12 00:00:00.
Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.
Medusa: A novel gene drive system for confined suppression of insect populations
4146Marshall, JMH, B. A., PLOS One, 9:e102694. 2014-01-04 00:00:00.
Gene drive systems provide novel opportunities for insect population suppression by driving genes that confer a fitness cost into pest or disease vector populations; however regulatory issues arise when genes are capable of spreading across international borders. Gene drive systems displaying threshold properties provide a solution since they can be confined to local populations and eliminated through dilution with wild-types. We propose a novel, threshold-dependent gene drive system, Medusa, capable of inducing a local and reversible population crash. Medusa consists of four components - two on the X chromosome, and two on the Y chromosome. A maternally-expressed, X-linked toxin and a zygotically-expressed, Y-linked antidote results in suppression of the female population and selection for the presence of the transgene-bearing Y because only male offspring of Medusa-bearing females are protected from the effects of the toxin. At the same time, the combination of a zygotically-expressed, Y-linked toxin and a zygotically-expressed, X-linked antidote selects for the transgene-bearing X in the presence of the transgene-bearing Y. Together these chromosomes create a balanced lethal system that spreads while selecting against females when present above a certain threshold frequency. Simple population dynamic models show that an all-male release of Medusa males, carried out over six generations, is expected to induce a population crash within 12 generations for modest release sizes on the order of the wild population size. Re-invasion of non-transgenic insects into a suppressed population can result in a population rebound; however this can be prevented through regular releases of modest numbers of Medusa males. Finally, we outline how Medusa could be engineered with currently available molecular tools.
The organization and evolution of the Responder satellite in species of the Drosophila melanogaster group: dynamic evolution of a target of meiotic drive
4145Larracuente, AM, BMC Evolutionary Biology, 14:233. 2014-01-03 00:00:00.
: Satellite DNA can make up a substantial fraction of eukaryotic genomes and has roles in genome structure and chromosome segregation. The rapid evolution of satellite DNA can contribute to genomic instability and genetic incompatibilities between species. Despite its ubiquity and its contribution to genome evolution, we currently know little about the dynamics of satellite DNA evolution. The Responder (Rsp) satellite DNA family is found in the pericentric heterochromatin of chromosome 2 of Drosophila melanogaster. Rsp is well-known for being the target of Segregation Distorter (SD) an autosomal meiotic drive system in D. melanogaster. I present an evolutionary genetic analysis of the Rsp family of repeats in D. melanogaster and its closely-related species in the melanogaster group (D. simulans, D. sechellia, D. mauritiana, D. erecta, and D. yakuba) using a combination of available BAC sequences, whole genome shotgun Sanger reads, Illumina short read deep sequencing, and fluorescence in situ hybridization. Results: I show that Rsp repeats have euchromatic locations throughout the D. melanogaster genome, that Rsp arrays show evidence for concerted evolution, and that Rsp repeats exist outside of D. melanogaster, in the melanogaster group. The repeats in these species are considerably diverged at the sequence level compared to D. melanogaster, and have a strikingly different genomic distribution, even between closely-related sister taxa. Conclusions: The genomic organization of the Rsp repeat in the D. melanogaster genome is complex it exists of large blocks of tandem repeats in the heterochromatin and small blocks of tandem repeats in the euchromatin. My discovery of heterochromatic Rsp-like sequences outside of D. melanogaster suggests that SD evolved after its target satellite and that the evolution of the Rsp satellite family is highly dynamic over a short evolutionary time scale (<240,000 years).
Guidance on the environmental risk assessment of genetically modified animals
16055European Food Safety Authority, European Food Safety Authority, 2013-05-23 20:45:04.
This document describes the six sequential steps for the ERA of GM animals, as indicated in Directive 2001/18/EC: (1) problem formulation including hazard and exposure identification; (2) hazard characterisation; (3) exposure characterisation; (4) risk characterisation; (5) risk management strategies; and (6) an overall risk evaluation. The Scientific Panel on Genetically Modified Organisms of the European Food Safety Authority follows Annex II of Directive 2001/18/EC, considering specific areas of risk to be addressed by applicants and risk assessors during the ERA of GM fish, GM insects and GM mammals and birds.
Elimination of Y chromosome-bearing spermatids during spermiogenesis in an autosomal sex-ratio mutant of Drosophila simulans
4183Yasuno, YI, Y. H.; Yamamoto, M. T., Genes & Genetic Systems, 88:113-126. 2013-01-21 00:00:00.
Sex ratio distortion, which is commonly abbreviated as sex-ratio, has been studied in many Drosophila species, but the mechanism remains largely unknown. Here, we report on the sex-ratio mutant of D. simulans named excess of females (exf). The third chromosomal recessive mutation results in a sex ratio of approximately 0.2 or less (males/total). Cytological observation demonstrated that meiosis appeared to be completed normally, but that most Y chromosome-bearing nuclei failed to elongate during spermiogenesis, as revealed by fluorescence in situ hybridization using sex chromosome-specific probes. These aberrant nuclei contained membranous inclusions as revealed by electron microscopic analysis. Most of the aberrant exf spermatids failed to individualize and mature, suggesting that a later stage of spermiogenesis is involved in prevention of production of sperm with abnormal morphology. On the one hand, in exf seminal vesicles, sperm nuclei with a length of 5-8.5 mu m were occasionally observed, in addition to those with wild-type sperm dimensions, that is, a length of approximately 10 mu m. Thus, spermatids with less severe nuclear defects can escape elimination and be released into the seminal vesicles as mature sperm. Furthermore, we constructed His2AvD-GFP and ProtamineB-eGFP transgenic lines in D. simulans, and examined the processes involved in replacement of chromatin proteins over a time course, according to nuclear morphology. We found that both normal and abnormal sperm heads demonstrated equal chromatin replacement during late spermiogenesis. Our results suggest that exf belongs to a unique class of meiotic drive systems in that (1) intranuclear membranous inclusions cause failure of nuclear shaping of Y-bearing spermatids without affecting the histone-protamine transition, and (2) a portion of the aberrant spermatids differentiate into mature sperm; these are transferred to and stored by females.
Modelling the spatial spread of a homing endonuclease gene in a mosquito population
4177North, AB, A.; Godfray, H. C. J., Journal of Applied Ecology, 50:1216-1225. 2013-01-15 00:00:00.
Homing endonuclease genes (HEGs) exist naturally in many single-celled organisms and can show extremely strong genetic drive allowing them to spread through populations into which they are introduced. They are being investigated as tools to manipulate the populations of important vectors of human disease, in particular the mosquitoes that transmit malaria. Before HEGs can be deployed, it is important to study their spatial spread in order to design efficient release strategies. A spatially explicit model is developed to study the spread of a HEG through a landscape whose structure is defined by the distribution of mosquito breeding and feeding sites. The model is motivated by the biology of the major vectors of malaria in Africa. The conditions for spread, fixation and loss of two major types of HEG are explored in different landscapes. In landscapes where mosquito resources are abundant, the conditions for spread are well approximated by a mean-field model. Where a HEG imposes a genetic load, it can cause population extinction, though spatial models more often predict population suppression. In certain types of landscapes where mosquito resources are rare, an introduced HEG may be prevented from moving between local mosquito populations and so a simple release strategy is unlikely to be effective, yet if the HEG succeeds in spreading population extinction is a feasible outcome. Increasing the number of release sites at the expense of releasing fewer mosquitoes per site reduces the probability that a HEG will fail.Synthesis and applications. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study.
Spread of a new parasitic B chromosome variant is facilitated by high gene flow
4176Manrique-Poyato, MIL-L, M. D.; Cabrero, J.; Perfectti, F.; Camacho, J. P. M., PLOS One, 8:e83712. 2013-01-14 00:00:00.
The B-24 chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B-24 frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise N(e)m estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B-24 diffusion both eastward and westward, with minor role for B-24 drive due to the arrival of drive suppressor genes which are also frequent in the donor population.
Modeling the dynamics of a non-limited and a self-limited gene drive system in structured Aedes aegypti populations
4175Legros, MX, C. G.; Morrison, A.; Scott, T. W.; Lloyd, A. L.; Gould, F., PLOS One, 8:e83354. 2013-01-13 00:00:00.
Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local vector populations. Because of the potential of these selfish elements to spread through populations, control approaches based on these strategies must be carefully evaluated to ensure a balance between the desirable spread of the refractoriness-conferring genetic cargo and the avoidance of potentially unwanted outcomes such as spread to non-target populations. There is also a need to develop better estimates of the economics of such releases. We present here an evaluation of two such strategies using a biologically realistic mathematical model that simulates the resident Aedes aegypti mosquito population of Iquitos, Peru. One strategy uses the selfish element Medea, a non-limited element that could permanently spread over a large geographic area; the other strategy relies on Killer-Rescue genetic constructs, and has been predicted to have limited spatial and temporal spread. We simulate various operational approaches for deploying these genetic strategies, and quantify the optimal number of released transgenic mosquitoes needed to achieve definitive spread of Medea-linked genes and/or high frequencies of Killer-Rescue-associated elements. We show that for both strategies the most efficient approach for achieving spread of anti-pathogen genes within three years is generally to release adults of both sexes in multiple releases over time. Even though females in these releases should not transmit disease, there could be public concern over such releases, making the less efficient male-only release more practical. This study provides guidelines for operational approaches to population replacement genetic strategies, as well as illustrates the use of detailed spatial models to assist in safe and efficient implementation of such novel genetic strategies.
Mutations to the piRNA Pathway Component Aubergine Enhance Meiotic Drive of Segregation Distorter in Drosophila melanogaster
4172Gell, SLR, R. A., Genetics, 193:771-784. 2013-01-10 00:00:00.
Diploid sexual reproduction involves segregation of allelic pairs, ensuring equal representation of genotypes in the gamete pool. Some genes, however, are able to "cheat" the system by promoting their own transmission. The Segregation distorter (Sd) locus in Drosophila melanogaster males is one of the best-studied examples of this type of phenomenon. In this system the presence of Sd on one copy of chromosome 2 results in dysfunction of the non-Sd-bearing (Sd(+)) sperm and almost exclusive transmission of Sd to the next generation. The mechanism by which Sd wreaks such selective havoc has remained elusive. However, its effect requires a target locus on chromosome 2 known as Responder (Rsp). The Rsp locus comprises repeated copies of a satellite DNA sequence and Rsp copy number correlates with sensitivity to Sd. Under distorting conditions during spermatogenesis, nuclei with chromosomes containing greater than several hundred Rsp repeats fail to condense chromatin and are eliminated. Recently, Rsp sequences were found as small RNAs in association with Argonaute family proteins Aubergine (Aub) and Argonaute3 (AGO3). These proteins are involved in a germ-line-specific RNAi mechanism known as the Piwi-interacting RNA (piRNA) pathway, which specifically suppresses transposon activation in the germline. Here, we evaluate the role of piRNAs in segregation distortion by testing the effects of mutations to piRNA pathway components on distortion. Further, we specifically targeted mutations to the aub locus of a Segregation Distorter (SD) chromosome, using ends-out homologous recombination. The data herein demonstrate that mutations to piRNA pathway components act as enhancers of SD.
The design and in vivo evaluation of engineered I-OnuI-based enzymes for HEG gene drive
4169Chan, YST, R.; Jarjour, J.; Huen, D. S.; Stoddard, B. L.; Russell, S., PLOS One, 8:e74254. 2013-01-07 00:00:00.
The homing endonuclease gene (HEG) drive system, a promising genetic approach for controlling arthropod populations, utilises engineered nucleases to spread deleterious mutations that inactivate individual genes throughout a target population. Previous work with a naturally occurring LAGLIDADG homing endonuclease (I-SceI) demonstrated its feasibility in both Drosophila and Anopheles. Here we report on the next stage of this strategy: the redesign of HEGs with customized specificity in order to drive HEG-induced 'homing' in vivo via break-induced homologous recombination. Variants targeting a sequence within the Anopheles AGAP004734 gene were created from the recently characterized I-OnuI endonuclease, and tested for cleavage activity and frequency of homing using a model Drosophila HEG drive system. We observed cleavage and homing at an integrated reporter for all endonuclease variants tested, demonstrating for the first time that engineered HEGs can cleave their target site in insect germline cells, promoting targeted mutagenesis and homing. However, in comparison to our previously reported work with I-SceI, the engineered I-OnuI variants mediated homing with a reduced frequency, suggesting that site-specific cleavage activity is insufficient by itself to ensure efficient homing. Taken together, our experiments take a further step towards the development of a viable HEG-based population control strategy for insects.
Optimising homing endonuclease gene drive performance in a semi-refractory species: The Drosophila melanogaster experience
4168Chan, YSH, D. S.; Glauert, R.; Whiteway, E.; Russell, S., PLOS One, 8:e54130. 2013-01-06 00:00:00.
Homing endonuclease gene (HEG) drive is a promising insect population control technique that employs meganucleases to impair the fitness of pest populations. Our previous studies showed that HEG drive was more difficult to achieve in Drosophila melanogaster than Anopheles gambiae and we therefore investigated ways of improving homing performance in Drosophila. We show that homing in Drosophila responds to increased expression of HEGs specifically during the spermatogonia stage and this could be achieved through improved construct design. We found that 39-UTR choice was important to maximise expression levels, with HEG activity increasing as we employed Hsp70, SV40, vasa and beta Tub56D derived UTRs. We also searched for spermatogonium-specific promoters and found that the Rcd-1r promoter was able to drive specific expression at this stage. Since Rcd-1 is a regulator of differentiation in other species, it suggests that Rcd-1r may serve a similar role during spermatogonial differentiation in Drosophila. Contrary to expectations, a fragment containing the entire region between the TBPH gene and the bgcn translational start drove strong HEG expression only during late spermatogenesis rather than in the germline stem cells and spermatogonia as expected. We also observed that the fraction of targets undergoing homing was temperature-sensitive, falling nearly four-fold when the temperature was lowered to 18 degrees C. Taken together, this study demonstrates how a few simple measures can lead to substantial improvements in the HEG-based gene drive strategy and reinforce the idea that the HEG approach may be widely applicable to a variety of insect control programs.
Natural variation of the Y chromosome suppresses sex ratio distortion and modulates testis-specific gene expression in Drosophila simulans
4167Branco, ATT, Y.; Hartl, D. L.; Lemos, B., Heredity, 111:8-15. 2013-01-05 00:00:00.
X-linked sex-ratio distorters that disrupt spermatogenesis can cause a deficiency in functional Y-bearing sperm and a female-biased sex ratio. Y-linked modifiers that restore a normal sex ratio might be abundant and favored when a X-linked distorter is present. Here we investigated natural variation of Y-linked suppressors of sex-ratio in the Winters systems and the ability of these chromosomes to modulate gene expression in Drosophila simulans. Seventy-eight Y chromosomes of worldwide origin were assayed for their resistance to the X-linked sex-ratio distorter gene Dox. Y chromosome diversity caused males to sire similar to 63% to similar to 98% female progeny. Genome-wide gene expression analysis revealed hundreds of genes differentially expressed between isogenic males with sensitive (high sex ratio) and resistant (low sex ratio) Y chromosomes from the same population. Although the expression of about 75% of all testis-specific genes remained unchanged across Y chromosomes, a subset of post-meiotic genes was upregulated by resistant Y chromosomes. Conversely, a set of accessory gland-specific genes and mitochondrial genes were downregulated in males with resistant Y chromosomes. The D. simulans Y chromosome also modulated gene expression in XXY females in which the Y-linked protein-coding genes are not transcribed. The data suggest that the Y chromosome might exert its regulatory functions through epigenetic mechanisms that do not require the expression of protein-coding genes. The gene network that modulates sex ratio distortion by the Y chromosome is poorly understood, other than that it might include interactions with mitochondria and enriched for genes expressed in post-meiotic stages of spermatogenesis.
Local dynamics of a fast-evolving sex-ratio system in Drosophila simulans
4166Bastide, HG, P. R.; Ogereau, D.; Cazemajor, M.; Montchamp-Moreau, C., Molecular Ecology, 22:5352-5367. 2013-01-04 00:00:00.
By distorting Mendelian transmission to their own advantage, X-linked meiotic drive elements can rapidly spread in natural populations, generating a sex-ratio bias. One expected consequence is the triggering of a co-evolutionary arms race between the sex chromosome that carries the distorter and suppressors counteracting its effect. Such an arms race has been theoretically and experimentally established and can have many evolutionary consequences. However, its dynamics in contemporary populations is still poorly documented. Here, we investigate the fate of the young X-linked Paris driver in Drosophila simulans from sub-Saharan Africa to the Middle East. We provide the first example of the early dynamics of distorters and suppressors: we find consistent evidence that the driving chromosomes have been rising in the Middle East during the last decade. In addition, identical haplotypes are at high frequencies around the two co-evolving drive loci in remote populations, implying that the driving X chromosomes share a recent common ancestor and suggesting that East Africa could be the cradle of the Paris driver. The segmental duplication associated with drive presents an unusual structure in West Africa, which could reflect a secondary state of the driver. Together with our previous demonstration of driver decline in the Indian Ocean where suppression is complete, these data provide a unique picture of the complex dynamics of a co-evolutionary arms race currently taking place in natural populations of D.simulans.
Germline excision of transgenes in Aedes aegypti by homing endonucleases
4165Aryan, AA, M. A. E.; Myles, K. M.; Adelman, Z. N., Scientific Reports, 3:1603. 2013-01-03 00:00:00.
Aedes (Ae.) aegypti is the primary vector for dengue viruses (serotypes1-4) and chikungunya virus. Homing endonucleases (HEs) are ancient selfish elements that catalyze double-stranded DNA breaks (DSB) in a highly specific manner. In this report, we show that the HEs Y2-I-AniI, I-CreI and I-SceI are all capable of catalyzing the excision of genomic segments from the Ae. aegypti genome in a heritable manner. Y2-I-AniI demonstrated the highest efficiency at two independent genomic targets, with 20-40% of Y2-I-AniI-treated individuals producing offspring that had lost the target transgene. HE-induced DSBs were found to be repaired via the single-strand annealing (SSA) and non-homologous end-joining (NHEJ) pathways in a manner dependent on the availability of direct repeat sequences in the transgene. These results support the development of HE-based gene editing and gene drive strategies in Ae. aegypti, and confirm the utility of HEs in the manipulation and modification of transgenes in this important vector.
A Synthetic Gene Drive System for Local, Reversible Modification and Suppression of Insect Populations
4164Akbari, OSM, K. D.; Marshall, J. M.; Huang, H. X.; Ward, C. M.; Hay, B. A., Current Biology, 23:671-677. 2013-01-02 00:00:00.
Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a self-perpetuating method of disease prevention but requires a gene drive mechanism to spread these traits to high frequency [1-3]. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread are attractive because they bring about local but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals [4-6]. These features are likely to be important in many social and regulatory contexts [7-10]. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal-effect lethal underdominance (UDMEL), in which two maternally expressed toxins, located on separate chromosomes, are each linked with a zygotic antidote able to rescue maternal-effect lethality of the other toxin. We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. Models suggest that transgene spread can often be limited to local environments. They also show that in a population in which single-locus UDMEL has been carried out, repeated release of wild-type males can result in population suppression, a novel method of genetic population manipulation.
Genetic mapping a meiotic driver that causes sex ratio distortion in the mosquito Aedes aegypti
4195Shin, DM, A.; Severson, D. W., Journal of Heredity, 103:303-307. 2012-01-13 00:00:00.
An endogenous meiotic driver in the dengue and yellow fever vector mosquito Aedes aegypti can cause highly male-biased sex ratio distortion in crosses from suitable genetic backgrounds. We previously selected a strain that carries a strong meiotic drive gene (D) linked with the maledetermining allele (M) on chromosome 1 in A. aegypti. Here, we performed segregation analysis of the M-D locus among backcross (BC1) progeny from a driver male and drive- sensitive females. Assessment of sex ratios among BC2 progeny showed; similar to 5.2% recombination between the M-D locus and the sex determination locus. Multipoint linkage mapping across this region revealed consistent marker orders and recombination frequencies with the existing reference linkage map and placed the M-D locus within a 6.5-cm interval defined by the LF159 locus and microsatellite marker 446GAA, which should facilitate future positional cloning efforts.
Confinement of gene drive systems to local populations: A comparative analysis
4192Marshall, JMH, B. A., Journal of Theoretical Biology, 294:153-171. 2012-01-10 00:00:00.
Mosquito-borne diseases such as malaria and dengue fever pose a major health problem through much of the world. One approach to disease prevention involves the use of selfish genetic elements to drive disease-refractory genes into wild mosquito populations. Recently engineered synthetic drive systems have provided encouragement for this strategy; but at the same time have been greeted with caution over the concern that transgenes may spread into countries and communities without: their consent. Consequently, there is also interest in gene drive systems that, while strong enough to bring about local population replacement, are unable to establish themselves beyond a partially isolated release site, at least during the testing phase. Here, we develop simple deterministic and stochastic models to compare the confinement properties of a variety of gene drive systems. Our results highlight several systems with desirable features for confinement-a high migration rate required to become established in neighboring populations, and low-frequency persistence in neighboring populations for moderate migration rates. Single-allele underdominance and single-locus engineered underdominance have the strongest confinement properties, but are difficult to engineer and require a high introduction frequency, respectively. Toxin-antidote systems such as Semele. Merea and two-locus engineered underdominance show promising confinement properties and require lower introduction frequencies. Killer-rescue is self-limiting in time, but is able to disperse to significant levels in neighboring populations. We discuss the significance of these results in the context of a phased release of transgenic mosquitoes, and the need for characterization of local ecology prior to a release. (C) 2011 Elsevier Ltd. All rights reserved.
The Selfish Segregation Distorter Gene Complex of Drosophila melanogaster
4190Larracuente, AMP, D. C., Genetics, 192:33-53. 2012-01-08 00:00:00.
Segregation Distorter (SD) is an autosomal meiotic drive gene complex found worldwide in natural populations of Drosophila melanogaster. During spermatogenesis, SD induces dysfunction of SD+ spermatids so that SD/SD+ males sire almost exclusively SD-bearing progeny rather than the expected 1:1 Mendelian ratio. SD is thus evolutionarily "selfish," enhancing its own transmission at the expense of its bearers. Here we review the molecular and evolutionary genetics of SD. Genetic analyses show that the SD is a multilocus gene complex involving two key loci-the driver, Segregation distorter (Sd), and the target of drive, Responder (Rsp)-and at least three upward modifiers of distortion. Molecular analyses show that Sd encodes a truncated duplication of the gene RanGAP, whereas Rsp is a large pericentromeric block of satellite DNA. The Sd-RanGAP protein is enzymatically wild type but mislocalized within cells and, for reasons that remain unclear, appears to disrupt the histone-to-protamine transition in drive-sensitive spermatids bearing many Rsp satellite repeats but not drive-insensitive spermatids bearing few or no Rsp satellite repeats. Evolutionary analyses show that the Sd-RanGAP duplication arose recently within the D. melanogaster lineage, exploiting the preexisting and considerably older Rsp satellite locus. Once established, the SD haplotype collected enhancers of distortion and suppressors of recombination. Further dissection of the molecular genetic and cellular basis of SD-mediated distortion seems likely to provide insights into several important areas currently understudied, including the genetic control of spermatogenesis, the maintenance and evolution of satellite DNAs, the possible roles of small interfering RNAs in the germline, and the molecular population genetics of the interaction of genetic linkage and natural selection.
Local selection underlies the geographic distribution of sex-ratio drive in Drosophila neotestacea
4186Dyer, KA, Evolution, 66:973-984. 2012-01-04 00:00:00.
Selfish genetic elements promote their own transmission to the next generation, often at a cost to the host individual. A sex-ratio (SR) driving X chromosome prevents the maturation of Y-bearing sperm, and as a result is transmitted to 100% of the offspring, all of which are female. Because the spread of a SR chromosome can result in a female-biased population sex ratio, the ecological and evolutionary consequences of harboring this selfish element can be severe. In this study, we show that the prevalence of SR drive in Drosophila neotestacea varies between 0% and 30% among populations, and is common in the south whereas rare in the north. The prevalence of SR is not associated with the presence of suppressors of drive, geographic distance, or genetic distance based on autosomal microsatellite loci. Instead, our results indicate that ecological selection on SR drive varies among populations, as the prevalence of SR is highly correlated with climatic factors, with the severity of winter the best determinant of SR frequency. Thus, ecological and demographic factors may have significant consequences for the short and long term evolutionary dynamics of selfish elements and the manner with which they coevolve with the rest of the genome.
Scrambling eggs: Meiotic drive and the evolution of female recombination rates
4185Brandvain, YC, G., Genetics, 190:709-723. 2012-01-03 00:00:00.
Theories to explain the prevalence of sex and recombination have long been a central theme of evolutionary biology. Yet despite decades of attention dedicated to the evolution of sex and recombination, the widespread pattern of sex differences in the recombination rate is not well understood and has received relatively little theoretical attention. Here, we argue that female meiotic drivers-alleles that increase in frequency by exploiting the asymmetric cell division of oogenesis-present a potent selective pressure favoring the modification of the female recombination rate. Because recombination plays a central role in shaping patterns of variation within and among dyads, modifiers of the female recombination rate can function as potent suppressors or enhancers of female meiotic drive. We show that when female recombination modifiers are unlinked to female drivers, recombination modifiers that suppress harmful female drive can spread. By contrast, a recombination modifier tightly linked to a driver can increase in frequency by enhancing female drive. Our results predict that rapidly evolving female recombination rates, particularly around centromeres, should be a common outcome of meiotic drive. We discuss how selection to modify the efficacy of meiotic drive may contribute to commonly observed patterns of sex differences in recombination.
Requirements for effective malaria control with homing endonuclease genes
4203Deredec, AG, H. C. J.; Burt, A., Proceedings of the National Academy of Sciences of the United States of America, 108:e874-e880. 2011-01-21 00:00:00.
Malaria continues to impose a substantial burden on human health. We have previously proposed that biological approaches to control the mosquito vector of disease could be developed using homing endonuclease genes (HEGs), a class of selfish or parasitic gene that exists naturally in many microbes. Recent lab studies have demonstrated that HEGs can function in mosquitoes. We constructed and analyzed a model of mosquito population genetics and malaria epidemiology to determine how well HEGs need to function in order to have a significant effect on the burden of disease. Our model, combined with currently available data, indicates that populations of Anopheles gambiae could be eliminated by releasing 2-3 HEGs targeting female fertility genes, or a driving-Y chromosome that is transmitted to 75-96% of progeny. Combinations of fertility-targeting HEGs and Y drive may also be effective. It is possible to eliminate the disease without eliminating the vector, but the parameter space producing this outcome appears to be small. HEGs causing a quantitative reduction in adult survival can be more effective than those targeting female fertility, but the selection coefficients that need to be imposed are still large, unless many HEGs are to be released. Simulations show that HEG-based strategies can be effective over socially relevant time frames. Important limiting assumptions of the models are that there is only a single vector species, and we model a homogeneous population, not a landscape. Nevertheless, we conclude that HEG-based approaches could have a transformational effect on malaria control efforts.
Reduced polymorphism associated with X chromosome meiotic drive in the stalk-eyed fly Teleopsis dalmanni
4202Christianson, SJB, C. L.; Wilkinson, G. S., PLOS One, 6:e27254. 2011-01-20 00:00:00.
Sex chromosome meiotic drive has been suggested as a cause of several evolutionary genetic phenomena, including genomic conflicts that give rise to reproductive isolation between new species. In this paper we present a population genetic analysis of X chromosome drive in the stalk-eyed fly, Teleopsis dalmanni, to determine how this natural polymorphism influences genetic diversity. We analyzed patterns of DNA sequence variation at two X-linked regions (comprising 1325 bp) approximately 50 cM apart and one autosomal region (comprising 921 bp) for 50 males, half of which were collected in the field from one of two allopatric locations and the other half were derived from lab-reared individuals with known brood sex ratios. These two populations are recently diverged but exhibit partial postzygotic reproductive isolation, i.e. crosses produce sterile hybrid males and fertile females. We find no nucleotide or microsatellite variation on the drive X chromosome, whereas the same individuals show levels of variation at autosomal regions that are similar to field-collected flies. Furthermore, one field-caught individual collected 10 years previously had a nearly identical X haplotype to the drive X, and is over 2% divergent from other haplotypes sampled from the field. These results are consistent with a selective sweep that has removed genetic variation from much of the drive X chromosome. We discuss how this finding may relate to the rapid evolution of postzygotic reproductive isolation that has been documented for these flies.
Insect population control by homing endonuclease-based gene drive: An evaluation in Drosophila melanogaster
4201Chan, YSN, D. A.; Huen, D. S.; Russell, S., Genetics, 188:33-44. 2011-01-19 00:00:00.
Insects play a major role as vectors of human disease as well as causing significant agricultural losses. Harnessing the activity of customized homing endonuclease genes (HEGs) has been proposed as a method for spreading deleterious mutations through populations with a view to controlling disease vectors. Here, we demonstrate the feasibility of this method in Drosophila melanogaster, utilizing the well-characterized HEG, I-SceI. In particular, we show that high rates of homing can be achieved within spermatogonia and in the female germline. We show that homed constructs continue to exhibit HEG activity in the subsequent generation and that the ectopic homing events required for initiating the strategy occur at an acceptable rate. We conclude that the requirements for successful deployment of a HEG-based gene drive strategy can be satisfied in a model dipteran and that there is a reasonable prospect of the method working in other dipterans. In characterizing the system we measured repair outcomes at the spermatogonial, spermatocyte, and spermatid stages of spermatogenesis. We show that homologous recombination is restricted to spermatogonia and that it immediately ceases when they become primary spermatocytes, indicating that the choice of DNA repair pathway in the Drosophila testis can switch abruptly during differentiation.
Rapid rise and fall of selfish sex-ratio X Chromosomes in Drosophila simulans: Spatiotemporal analysis of phenotypic and molecular data
4199Bastide, HC, M.; Ogereau, D.; Derome, N.; Hospital, F.; Montchamp-Moreau, C., Molecular Biology and Evolution, 28:2461-2470. 2011-01-17 00:00:00.
Sex-ratio drive, which has been documented in several Drosophila species, is induced by X-linked segregation distorters. Contrary to Mendel's law of independent assortment, the sex-ratio chromosome (X(SR)) is inherited by more than half the offspring of carrier males, resulting in a female-biased sex ratio. This segregation advantage allows X(SR) to spread in populations, even if it is not beneficial for the carriers. In the cosmopolitan species D. simulans, the Paris sex-ratio is caused by recently emerged selfish X(SR) chromosomes. These chromosomes have triggered an intragenomic conflict, and their propagation has been halted over a large area by the evolution of complete drive suppression. Previous molecular population genetics analyses revealed a selective sweep indicating that the invasion of X(SR) chromosomes was very recent in Madagascar (likely less than 100 years ago). Here, we show that X(SR) chromosomes are now declining at this location as well as in Mayotte and Kenya. Drive suppression is complete in the three populations, which display little genetic differentiation and share swept haplotypes, attesting to a common and very recent ancestry of the X(SR) chromosomes. Patterns of DNA sequence variation also indicate a fitness cost of the segmental duplication involved in drive. The data suggest that X(SR) chromosomes started declining first on the African continent, then in Mayotte, and finally in Madagascar and strongly support a scenario of rapid cycling of X chromosomes. Once drive suppression has evolved, standard X(ST) chromosomes locally replace costly X(SR) chromosomes in a few decades.
A synthetic homing endonuclease-based gene drive system in the human malaria mosquito
4211Windbichler, NM, M.; Papathanos, P. A.; Thyme, S. B.; Li, H.; Ulge, U. Y.; Hovde, B. T.; Baker, D.; Monnat, R. J.; Burt, A.; Crisanti, A., Nature, 473:212-215. 2011-01-09 00:00:00.
Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity(1-3). The development of genetically engineered malaria-resistant mosquitoes has shown, as a proof of principle, the possibility of targeting the mosquito's ability to serve as a disease vector(4-7). The translation of these achievements into control measures requires an effective technology to spread a genetic modification from laboratory mosquitoes to field populations(8). We have suggested previously that homing endonuclease genes (HEGs), a class of simple selfish genetic elements, could be exploited for this purpose(9). Here we demonstrate that a synthetic genetic element, consisting of mosquito regulatory regions(10) and the homing endonuclease gene I-SceI(11-13), can substantially increase its transmission to the progeny in transgenic mosquitoes of the human malaria vector Anopheles gambiae. We show that the I-SceI element is able to invade receptive mosquito cage populations rapidly, validating mathematical models for the transmission dynamics of HEGs. Molecular analyses confirm that expression of I-SceI in the male germline induces high rates of site-specific chromosomal cleavage and gene conversion, which results in the gain of the I-SceI gene, and underlies the observed genetic drive. These findings demonstrate a new mechanism by which genetic control measures can be implemented. Our results also show in principle how sequence-specific genetic drive elements like HEGs could be used to take the step from the genetic engineering of individuals to the genetic engineering of populations.
Transcript profiling of the meiotic drive phenotype in testis of Aedes aegypti using suppressive subtractive hybridization
4209Shin, DYJ, L. Z.; Lobo, N. F.; Severson, D. W., Journal of Insect Physiology, 57:1220-1226. 2011-01-07 00:00:00.
The meiotic drive gene in Aedes aegypti is tightly linked with the sex determination locus on chromosome 1, and causes highly male-biased sex ratios. We prepared cDNA libraries from testes from the Ae. aegypti 137 strain (driving) and RED strain (non-driving), and used suppressive subtraction hybridization techniques to enrich for 137 testes-specific transcripts. Expressed sequence tags (ESTs) were obtained from a total of 2784 randomly selected clones from the subtracted 137 (subT37) library as well as the primary libraries for each strain (pT37 and pRED). Sequence analysis identified a total of 171 unique genes in the subT37 library and 299 unique genes among the three libraries. The majority of genes enriched in the subT37 library were associated with signal transduction, development, reproduction, metabolic process and cell cycle functions. Further, as observed with meiotic drive systems in Drosophila and mouse, a number of these genes were associated with signaling cascades that involve the Ras superfamily of regulatory small GTPases. Differential expression of several of these genes was verified in Ae. aegypti pupal testes using qRT-PCR. This study increases our understanding of testes gene expression enriched in adult males from the meiotic drive strain as well as insights into the basic testes transcriptome in Ae. aegypti. (C) 2011 Elsevier Ltd. All rights reserved.
Semele: A Killer-male, rescue-female system for suppression and replacement of insect disease vector populations
4207Marshall, JMP, G. W.; Buchman, A. B.; Hay, B. A., Genetics, 187:535-551. 2011-01-05 00:00:00.
Two strategies to control mosquito-borne diseases, such as malaria and dengue fever, are reducing mosquito population sizes or replacing populations with disease-refractory varieties. We propose a genetic system, Semele, which may be used for both. Semele consists of two components: a toxin expressed in transgenic males that either kills or renders infertile wild-type female recipients and an antidote expressed in females that protects them from the effects of the toxin. An all-male release results in population suppression because wild-type females that mate with transgenic males produce no offspring. A release that includes transgenic females results in gene drive since females carrying the allele are favored at high population frequencies. We use simple population genetic models to explore the utility of the Semele system. We find that Semele can spread under a wide range of conditions, all of which require a high introduction frequency. This feature is desirable since transgenic insects released accidentally are unlikely to persist, transgenic insects released intentionally can be spatially confined, and the element can be removed from a population through sustained release of wild-type insects. We examine potential barriers to Semele gene drive and suggest molecular tools that could be used to build the Semele system.
Inverse Medea as a novel gene drive system for socal population replacement: A theoretical analysis
4206Marshall, JMH, B. A., Journal of Heredity, 102:336-341. 2011-01-04 00:00:00.
One strategy to control mosquito-borne diseases, such as malaria and dengue fever, on a regional scale is to use gene drive systems to spread disease-refractory genes into wild mosquito populations. The development of a synthetic Medea element that has been shown to drive population replacement in laboratory Drosophila populations has provided encouragement for this strategy but has also been greeted with caution over the concern that transgenes may spread into countries without their consent. Here, we propose a novel gene drive system, inverse Medea, which is strong enough to bring about local population replacement but is unable to establish itself beyond an isolated release site. The system consists of 2 genetic components-a zygotic toxin and maternal antidote-which render heterozygous offspring of wild-type mothers unviable. Through population genetic analysis, we show that inverse Medea will only spread when it represents a majority of the alleles in a population. The element is best located on an autosome and will spread to fixation provided any associated fitness costs are dominant and to very high frequency otherwise. We suggest molecular tools that could be used to build the inverse Medea system and discuss its utility for a confined release of transgenic mosquitoes.
Gene-drive into insect populations with age and spatial structure: a theoretical assessment
4205Huang, YXL, A. L.; Legros, M.; Gould, F., Evolutionary Applications, 4:415-428. 2011-01-03 00:00:00.
The potential benefits and risks of genetically engineered gene-drive systems for replacing wild pest strains with more benign strains must be assessed prior to any field releases. We develop a computer simulation model to assess the feasibility of using engineered underdominance constructs to drive transgenes into age- and spatially structured mosquito populations. Our practical criterion for success is the achievement of a transgene frequency of at least 0.80 within 3 years of release. The impacts of a number of parameters that may affect the success of gene-drive, such as the release area, release age, density-dependent larval survival, fitness cost of the engineered genes, and migration probability of adults, are examined. Results show that patchy release generally requires the release of fewer engineered insects to achieve success than central release. When the fitness cost is very low, central release covering 25% of the total area can be more effective than a completely uniform release over the whole area. This study demonstrates that to determine the best method of spatial release, and the total number of engineered insects that must be released, it is important to take into account the age and sex of the released insects and spatial structure of the population.
Changes in sperm tail development associated with Y chromosome meiotic drive leading to an excess of males in the medfly Ceratitis capitata (Diptera: Tephritidae)
4218Rendon, PAB, R. D.; Wood, R. J., Biological Journal of the Linnean Society, 101:351-359. 2010-01-16 00:00:00.
The Mediterranean fruit fly Ceratitis capitata (Wied.) normally produces the sexes in equal ratio but strains carrying the Y chromosome meiotic drive MP (male-producing) factor show an excess of males. This is associated with a loss of sperm, and abnormal sperm structure in terms of multiple axonemes, atypical numbers of mitochondrial derivatives, and sometimes an incorrect initial orientation of paracrystalline bodies to the axoneme. Sperms are bundled together within spermatocysts, and those with depleted content and abnormalities occur in the same MP testes as normal spermatocysts. The maximum number of sperms per cyst in control strains was 256, each with a single axoneme originating from a single centriole (kinetosome). The maximum per cyst in MP strains was also 256 but MP cysts contained up to 300 axonemes, providing evidence of multiplication of centrioles. The structural changes in MP sperm are discussed in relation to similar abnormalities reported in the mosquito Aedes aegypti inheriting the Y chromosome meiotic drive haplotype MD. The evolutionary significance of this phenomenon is considered. (C) 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101, 351-359.
Molecular signature of epistatic selection: interrogating genetic interactions in the sex-ratio meiotic drive of Drosophila simulans
4222Chevin, LMB, H.; Montchamp-Moreau, C.; Hospital, F., Genetics Research, 91:171-182. 2009-01-20 00:00:00.
Fine scale analyses Of signatures of selection allow assessing quantitative aspects of a Species' evolutionary genetic history, such as the strength of selection on genes. When several selected loci lie in the same genomic region, their epistatic interactions may also be investigated. Here. we Study how the neutral polymorphism pattern was shaped by two close recombining loci that cause 'sex-ratio' meiotic drive in Drosophila simulans, as an example of strong selection with potentially strong epistasis. We compare the polymorphism data observed in a natural population with the results of forward stochastic simulations under several contexts of epistasis between the candidate loci for the drive. We compute the likelihood of different possible scenarios. in order to determine which configuration is most consistent with the data. Our results highlight that fine scale analyses of well-chosen candidate genomic regions provide information-rich data that can be used to investigate the genotype-phenotype-fitness map. which can hardly be Studied in genome-wide analyses. We also emphasize that initial conditions and time of observation (here, time after the Interruption Of a partial selective sweep) are crucial parameters in the interpretation of real data, while these are often overlooked in theoretical studies.
Large-scale selective sweep among Segregation Distorter chromosomes in African populations Drosophila melanogaster
4229Presgraves, DCG, P. R.; Cherukuri, A.; Lyttle, T. W., PLOS Genetics, 5:e1000463. 2009-01-07 00:00:00.
Segregation Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 of Drosophila melanogaster that strongly distorts Mendelian transmission; heterozygous SD/SD(+) males sire almost exclusively SD-bearing progeny. Fifty years of genetic, molecular, and theory work have made SD one of the best-characterized meiotic drive systems, but surprisingly the details of its evolutionary origins and population dynamics remain unclear. Earlier analyses suggested that the SD system arose recently in the Mediterranean basin and then spread to a low, stable equilibrium frequency (1-5%) in most natural populations worldwide. In this report, we show, first, that SD chromosomes occur in populations in sub-Saharan Africa, the ancestral range of D. melanogaster, at a similarly low frequency (similar to 2%), providing evidence for the robustness of its equilibrium frequency but raising doubts about the Mediterranean-origins hypothesis. Second, our genetic analyses reveal two kinds of SD chromosomes in Africa: inversion-free SD chromosomes with little or no transmission advantage; and an African-endemic inversion-bearing SD chromosome, SD-Mal, with a perfect transmission advantage. Third, our population genetic analyses show that SD-Mal chromosomes swept across the African continent very recently, causing linkage disequilibrium and an absence of variability over 39% of the length of the second chromosome. Thus, despite a seemingly stable equilibrium frequency, SD chromosomes continue to evolve, to compete with one another, or evade suppressors in the genome.
The effect of gene drive on containment of transgenic mosquitoes
4227Marshall, JM, Journal of Theoretical Biology, 258:250-265. 2009-01-05 00:00:00.
Mosquito-borne diseases such as malaria and dengue fever continue to be a major health problem through Much of the world. Several new potential approaches to disease control utilize gene drive to spread anti-pathogen genes into the mosquito Population. Prior to a release, these projects will require trials in outdoor cages from which transgenic mosquitoes may escape, albeit in small numbers. Most genes introduced in small numbers are very likely to be lost from the environment; however, gene drive mechanisms enhance the invasiveness of introduced genes. Consequently, introduced transgenes may be more likely to persist than ordinary genes following an accidental release. Here, we develop stochastic models to analyze the loss probabilities for several gene drive mechanisms, including homing endonuclease genes, transposable elements, Medea elements, the intracellular bacterium Wolbachia, engineered underdominance genes, and meiotic drive. We find that Medea and Wolbachia present the best compromise between invasiveness and containment for the six gene drive systems Currently being considered for the control of mosquito-borne disease. Published by Elsevier Ltd.
Skeeter Buster: A stochastic, spatially explicit modeling tool for studying Aedes aegypti population replacement and population suppression strategies
4225Magori, KL, M.; Puente, M. E.; Focks, D. A.; Scott, T. W.; Lloyd, A. L.; Gould, F., PLOS Neglected Tropical Diseases, 3:e508. 2009-01-03 00:00:00.
Dengue is the most important mosquito-borne viral disease affecting humans. The only prevention measure currently available is the control of its vectors, primarily Aedes aegypti. Recent advances in genetic engineering have opened the possibility for a new range of control strategies based on genetically modified mosquitoes. Assessing the potential efficacy of genetic (and conventional) strategies requires the availability of modeling tools that accurately describe the dynamics and genetics of Ae. aegypti populations. Methodology/Principal findingsWe describe in this paper a new modeling tool of Ae. aegypti population dynamics and genetics named Skeeter Buster. This model operates at the scale of individual water-filled containers for immature stages and individual properties (houses) for adults. The biology of cohorts of mosquitoes is modeled based on the algorithms used in the non-spatial Container Inhabiting Mosquitoes Simulation Model (CIMSiM). Additional features incorporated into Skeeter Buster include stochasticity, spatial structure and detailed population genetics. We observe that the stochastic modeling of individual containers in Skeeter Buster is associated with a strongly reduced temporal variation in stage-specific population densities. We show that heterogeneity in container composition of individual properties has a major impact on spatial heterogeneity in population density between properties. We detail how adult dispersal reduces this spatial heterogeneity. Finally, we present the predicted genetic structure of the population by calculating F(ST) values and isolation by distance patterns, and examine the effects of adult dispersal and container movement between properties. Conclusions/SignificanceWe demonstrate that the incorporated stochasticity and level of spatial detail have major impacts on the simulated population dynamics, which could potentially impact predictions in terms of control measures. The capacity to describe population genetics confers the ability to model the outcome of genetic control methods. Skeeter Buster is therefore an important tool to model Ae. aegypti populations and the outcome of vector control measures.
Defects in nuclear transport enhance segregation distortion
4242McElroy, JMM, R. A.; McLean, J. R., Fly, 2:280-290. 2008-01-20 00:00:00.
The equal segregation of chromosomes into gametes is a central tenet of Mendelian genetics. It is this process that is responsible for generating predictable outcomes of crosses, as well as subjecting all chromosomes to the natural selective pressures that exert themselves on a population. Meiotic drive systems violate the principle, and result in a distortion of normal Mendelian ratios. Examples of such meiotic drive systems exist in many organisms, including insects, mammals and plants (reviewed in Lyttle).1 The most clearly understood of these is the Segregation Distorter (SD) system in Drosophila melanogaster. SD was first observed because males carrying one SD chromosome and one normal (SD+) chromosome failed to transmit the normal chromosome to their offspring, causing transmission ratios of near 100% of the SD chromosome.2 T
Broadening the application of evolutionarily based genetic pest management
4237Gould, F, Evolution, 62:500-510. 2008-01-15 00:00:00.
Insect- and tick-vectored diseases such as malaria, dengue fever, and Lyme disease cause human suffering, and current approaches for prevention are not adequate. Invasive plants and animals such as Scotch broom, zebra mussels, and gypsy moths continue to cause environmental damage and economic losses in agriculture and forestry Rodents transmit diseases and cause major pre- and postharvest losses, especially in less affluent countries. Each of these problems might benefit from the developing field of Genetic Pest Management that is conceptually based on principles of evolutionary biology This article briefly describes the history of this field, new molecular tools in this field, and potential applications of those tools. There will be a need for evolutionary biologists to interact with researchers and practitioners in a variety of other fields to determine the most appropriate targets for genetic pest management, the most appropriate methods for specific targets, and the potential of natural selection to diminish the effectiveness of genetic pest management. In addition to producing environmentally sustainable pest management solutions, research efforts in this area could lead to new insights about the evolution of selfish genetic elements in natural systems and will provide students with the opportunity to develop a more sophisticated understanding of the role of evolutionary biology in solving societal problems.
Selective sweeps in a 2-locus model for sex-ratio meiotic drive in Drosophila simulans
4235Derome, NB, E.; Ogereau, D.; Veuille, M.; Montchamp-Moreau, C., Molecular Biology and Evolution, 25:409-416. 2008-01-13 00:00:00.
A way to identify loci subject to positive selection is to detect the signature of selective sweeps in given chromosomal regions. It is revealed by the departure of DNA polymorphism patterns from the neutral equilibrium predicted by coalescent theory. We surveyed DNA sequence variation in a region formerly identified as causing "sex-ratio" meiotic drive in Drosophila simulans. We found evidence that this system evolved by positive selection at 2 neighboring loci, which thus appear to be required simultaneously for meiotic drive to occur. The 2 regions are approximately 150-kb distant, corresponding to a genetic distance of 0.1 cM. The presumably large transmission advantage of chromosomes carrying meiotic drive alleles at both loci has not erased the individual signature of selection at each locus. This chromosome fragment combines a high level of linkage disequilibrium between the 2 critical regions with a high recombination rate. As a result, 2 characteristic traits of selective sweeps-the reduction of variation and the departure from selective neutrality in haplotype tests-show a bimodal pattern. Linkage disequilibrium level indicates that, in the natural population from Madagascar used in this study, the selective sweep may be as recent as 100 years.
Guidance for contained field trials of vector mosquitoes engineered to contain a gene drive system: Recommendations of a scientific working group
4232Benedict, MDA, P.; Dobson, S.; Gottlieb, M.; Harrington, L.; Higgs, S.; James, A.; James, S.; Knols, B.; Lavery, J.; O'Neill, S.; Scott, T.; Takken, W.; Toure, Y.; Core Working Grp Guidance, Containe, Vector-Borne and Zoonotic Diseases, 8:127-166. 2008-01-10 00:00:00.
The following recommendations represent the response of a group of involved scientists to the need for guidance to aid researchers, government authorities, and community leaders as they consider the design and implementation of field trials to assess the safety and efficacy of genetic strategies for reducing the transmission of diseases by mosquito vectors. Guidance is provided for contained (caged) field trials of genetically-engineered (GE) vector mosquitoes that are fertile and contain novel genetic constructs designed to spread through natural mosquito populations (“gene drive systems”). An effort is made to raise the practical issues that must be considered in advance of such testing, provide generalized recommendations based on currently available information, and identify “points to consider” regarding additional information that may be required in order to make informed decisions on a case-by-case basis. This guidance is intended to clarify the pathway for further assessment of the potential utility of such GE mosquitoes as a tool for the improvement of public health in disease-endemic regions.
Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae
4247Windbichler, NP, P. A.; Crisanti, A., PLOS Genetics, 4:1-9. 2008-01-05 00:00:00.
We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome-carrying spermatozoa. Notably, these male mosquitoes also induced complete early dominant embryo lethality in crosses with wild-type females. Morphological and molecular data indicated that all spermatozoa, irrespectively of the inheritance of the transgene, carried a substantial amount of I-PpoI protein that could attack the maternally inherited chromosome X of the embryo. Besides the obvious implications for implementing vector control measures, our data demonstrated the feasibility of generating synthetic sex distorters and revealed the intriguing possibility of manipulating maternally inherited genes using wild-type sperm cells carrying engineered endonucleases.
Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos
4259Windbichler, NP, P. A.; Catteruccia, F.; Ranson, H.; Burt, A.; Crisanti, A., Nucleic Acids Research, 35:5922-5933. 2007-01-17 00:00:00.
Homing endonuclease genes (HEGs) are selfish genetic elements that combine the capability to selectively disrupt specific gene sequences with the ability to rapidly spread from a few individuals to an entire population through homologous recombination repair events. Because of these properties, HEGs are regarded as promising candidates to transfer genetic modifications from engineered laboratory mosquitoes to wild-type populations including Anopheles gambiae the vector of human malaria. Here we show that I-SceI and I-PpoI homing endonucleases cleave their recognition sites with high efficiency inA. gambiae cells and embryos and we demonstrate HEG-induced homologous and non-homologous repair events in a variety of functional assays. We also propose a gene drive system for mosquitoes that is based on our finding that I-PpoI cuts genomic rDNA located on the X chromosome in A. gambiae, which could be used to selectively incapacitate X-carrying spermatozoa thereby imposing a severe male-biased sex ratio.
Small steps or giant leaps for male-killers? Phylogenetic constraints to male-killer host shifts
4257Tinsley, MCM, M. E. N., BMC Evolutionary Biology, 7:e1000313. 2007-01-15 00:00:00.
Background: Arthropods are infected by a wide diversity of maternally transmitted microbes. Some of these manipulate host reproduction to facilitate population invasion and persistence. Such parasites transmit vertically on an ecological timescale, but rare horizontal transmission events have permitted colonisation of new species. Here we report the first systematic investigation into the influence of the phylogenetic distance between arthropod species on the potential for reproductive parasite interspecific transfer. Results: We employed a well characterised reproductive parasite, a coccinellid beetle male-killer, and artificially injected the bacterium into a series of novel species. Genetic distances between native and novel hosts were ascertained by sequencing sections of the 16S and 12S mitochondrial rDNA genes. The bacterium colonised host tissues and transmitted vertically in all cases tested. However, whilst transmission efficiency was perfect within the native genus, this was reduced following some transfers of greater phylogenetic distance. The bacterium's ability to distort offspring sex ratios in novel hosts was negatively correlated with the genetic distance of transfers. Male-killing occurred with full penetrance following within-genus transfers; but whilst sex ratio distortion generally occurred, it was incomplete in more distantly related species. Conclusion: This study indicates that the natural interspecific transmission of reproductive parasites might be constrained by their ability to tolerate the physiology or genetics of novel hosts. Our data suggest that horizontal transfers are more likely between closely related species. Successful bacterial transfer across large phylogenetic distances may require rapid adaptive evolution in the new species. This finding has applied relevance regarding selection of suitable bacteria to manipulate insect pest and vector populations by symbiont gene-drive systems.
A sex-ratio meiotic drive system in Drosophila simulans. I: An autosomal suppressor
4256Tao, YM, J. P.; Araripe, L.; Ke, Y.; Hartl, D. L., PLOS Biology, 5:2560-2575. 2007-01-14 00:00:00.
Sex ratio distortion (sex-ratio for short) has been reported in numerous species such as Drosophila, where distortion can readily be detected in experimental crosses, but the molecular mechanisms remain elusive. Here we characterize an autosomal sex-ratio suppressor from D. simulans that we designate as not much yang (nmy, polytene chromosome position 87F3). Nmy suppresses an X-linked sex-ratio distorter, contains a pair of near-perfect inverted repeats of 345 bp, and evidently originated through retrotransposition from the distorter itself. The suppression is likely mediated by sequence homology between the suppressor and distorter. The strength of sex-ratio is greatly enhanced by lower temperature. This temperature sensitivity was used to assign the sex-ratio etiology to the maturation process of the Y-bearing sperm, a hypothesis corroborated by both light microscope observations and ultrastructural studies. It has long been suggested that an X-linked sex-ratio distorter can evolve by exploiting loopholes in the meiotic machinery for its own transmission advantage, which may be offset by other changes in the genome that control the selfish distorter. Data obtained in this study help to understand this evolutionary mechanism in molecular detail and provide insight regarding its evolutionary impact on genomic architecture and speciation.
A sex-ratio meiotic drive system in Drosophila simulans. II: An X-linked distorter
4255Tao, YA, L.; Kingan, S. B.; Ke, Y.; Xiao, H.; Hartl, D. L., PLOS Biology, 5:2576-2588. 2007-01-13 00:00:00.
The evolution of heteromorphic sex chromosomes creates a genetic condition favoring the invasion of sex-ratio meiotic drive elements, resulting in the biased transmission of one sex chromosome over the other, in violation of Mendel's first law. The molecular mechanisms of sex-ratio meiotic drive may therefore help us to understand the evolutionary forces shaping the meiotic behavior of the sex chromosomes. Here we characterize a sex-ratio distorter on the X chromosome (Dox) in Drosophila simulans by genetic and molecular means. Intriguingly, Dox has very limited coding capacity. It evolved from another X-linked gene, which also evolved de nova. Through retrotransposition, Dox also gave rise to an autosomal suppressor, not much yang (Nmy). An RNA interference mechanism seems to be involved in the suppression of the Dox distorter by the Nmy suppressor. Double mutant males of the genotype dox; nmy are normal for both sex-ratio and spermatogenesis. We postulate that recurrent bouts of sex-ratio meiotic drive and its subsequent suppression might underlie several common features observed in the heterogametic sex, including meiotic sex chromosome inactivation and achiasmy.
Introducing desirable transgenes into insect populations using Y-linked meiotic drive – A theoretical assessment
4251Huang, YXM, K.; Lloyd, A. L.; Gould, F., Evolution, 61:717-726. 2007-01-09 00:00:00.
The use of genetic drive mechanisms to replace native mosquito genotypes with individuals bearing antipathogen transgenes is a potential strategy for repressing insect transmission of human diseases such as malaria and dengue. Antipathogen transgenes have been developed and tested, but efficient gene drive mechanisms are lacking. Here we theoretically assess the feasibility of introducing antipathogen genes into wild Aedes aegypti populations by using a naturally occurring meiotic drive system. We consider the release of males having both a Winked meiotic drive gene and an X-linked drive-insensitive response allele to which an antipathogen gene is linked. We use mathematical models and computer simulations to determine how the post-introduction dynamics of the antipathogen gene are affected by specific genetic characteristics of the system. The results show that when the natural population is uniformly sensitive to the meiotic drive gene, the antipathogen gene may be driven close to fixation if the fitness costs of the drive gene, the insensitive response allele, and the antipathogen gene are low. However, when the natural population has a small proportion of an X-linked insensitive response allele or an autosomal gene that strongly reduces the effect of the drive gene, the antipathogen gene does not spread if it has an associated fitness cost. Our modeling results provide a theoretical foundation for further experimental tests.
Introducing transgenes into insect populations using combined gene-drive strategies: Modeling and analysis
4250Huang, YXM, K.; Lloyd, A. L.; Gould, F., Insect Biochemistry and Molecular Biology, 37:1054-1063. 2007-01-08 00:00:00.
Engineered underdominance (EU), meiotic drive (MD) and Wolbachia have been proposed as mechanisms for driving anti-pathogen transgenes into natural populations of insect vectors of human diseases. EU can drive transgenes to high and stable frequencies but requires the release of sizeable numbers of engineered insects. MD and Wolbachia either cannot maintain high frequencies of transgenes or lack appropriate expression in critical tissues, but both can drive the transgenes to spread from very low initial frequencies. Here we use mathematical models to assess the utility of combining EU with MD or with Wolbachia. Under some conditions, the combination of EU and MD results in a more efficient transgene-drive strategy than either mechanism alone. This combined strategy could drive the transgenes to stable fixation and would require fewer released insects than EU alone, especially when only males are released. However, a combination of EU and Wolbachia does not work better than EU alone because it requires the release of even more engineered insects. (C) 2007 Elsevier Ltd. All rights reserved.
Chromosome-wide linkage disequilibrium as a consequence of meiotic drive
4249Dyer, KAC, B.; Jaenike, J., Proceedings of the National Academy of Sciences of the United States of America, 104:1587-1592. 2007-01-07 00:00:00.
Adaptation by natural selection proceeds most efficiently when alleles compete solely on the basis of their effects on the survival and reproduction of their carriers. A major condition for this is equal Mendelian segregation, but meiotic drive can short-circuit this process. The evolution of drive often involves multiple, interacting genetic components, together with enhancers and suppressors of drive. Chromosomal inversions that suppress crossing over are also frequently associated with drive systems. This study investigates the effects of these processes on patterns of molecular evolution in the fly Drosophila recens, which is polymorphic for a driving X chromosome (X-D). Whereas standard wild-type chromosomes exhibit high levels of polymorphism at multiple loci, all of the X-D chromosomes effectively carry a single multilocus haplotype that spans at least 130 cM. The X-D is associated with a complex set of inversions that completely suppresses recombination between the standard wild-type chromosome and X-D in heterozygous females, which maintain nonrandom associations among loci that presumably interact epistatically for the expression of drive. The long-term costs of foregoing recombination may be substantial; in combination with its low equilibrium frequency, this makes the XD chromosome susceptible to the accumulation of deleterious mutations. Consistent with this, X-D chromosomes are apparently fixed for a recessive mutation that causes female sterility. Thus, the X-D in D. recens appears to be in chromosome-wide linkage disequilibrium and in the early stages of mutational degradation.
Cage trials using an endogenous meiotic drive gene in the mosquito Aedes aegypti to promote population replacement
4262Cha, SJM, A.; Chadee, D. D.; Severson, D. W., American Journal of Tropical Medicine and Hygiene, 74:62-68. 2006-01-20 00:00:00.
Control of arthropod-borne diseases based on population replacement with genetically modified noncompetent vectors has been proposed as a promising alternative to conventional control strategies. Due to likely fitness costs associated with vectors manipulated to carry anti-pathogen effector genes, the effector genes will need to be coupled with a strong drive system to rapidly sweep them into natural populations. Endogenous meiotic drive systems have strong and stable population replacement potential, and have previously been reported in two mosquito species: Aedes aegypti and Culex pipiens. To investigate the influence of an endogenous meiotic drive gene on Ae. aegypti population dynamics, we established three experimental population types that were initiated with 100%, 10%, and 1% male mosquitoes carrying a strong meiotic driver (T37 strain) and 100% sensitive females (RED strain), respectively. Among the 100% and 10% populations, early generations were highly male biased, which reflected the effects of the meiotic driver, and remained more than 60% male by the F-15. A genetic marker tightly linked with the meiotic driver on chromosome 1 showed strong selection for the T37 strain-specific allele. Similar but reduced effects of the meiotic driver were also observed in the 1% populations. These results suggest that release of A e. aegypti males carrying a strong meiotic driver into drive sensitive populations can be an effective tool for population replacement, and provide a foundation for additional studies including both experimental populations and simulations by mathematical modeling.
Isolation and characterization of the RanGAP gene in the mosquito Aedes aegypti
4261Cha, SJL, N.; Debruyn, B.; Severson, D. W., DNA Sequence, 17:223-230. 2006-01-19 00:00:00.
A duplicated 3'-truncated version of RanGAP was previously identified as Segregation distorter (Sd), the meiotic drive gene in Drosophila melanogaster. Here we report the cloning and characterization of the complete gene sequence for the RanGAP homolog from the mosquito Aedes aegypti. The 1995 bp cDNA sequence consists of a 113 bp 5'UTR and 130 bp 3'UTR, and encodes a 583 amino acid protein with high sequence identity with RanGAP homologues of several species. A 20,125 bp genomic DNA sequence contains the complete RanGAP gene, consisting of three exons and two introns. Intron 2 comprises 18,082 bp and contains multiple repetitive elements as well as putative coding regions. The RanGAP locus was mapped to the q-arm of chromosome 2. Because the meiotic drive gene (M-D) in A. aegpti was previously shown to be tightly linked with the sex determining locus on chromosome 1, RanGAP is likely not the M-D gene.
Population dynamics of an endogenous meiotic drive system in Aedes aegypti in Trinidad
4260Cha, SJC, D. D.; Severson, D. W., American Journal of Tropical Medicine and Hygiene, 75:70-77. 2006-01-18 00:00:00.
An endogenous meiotic drive system was previously reported to be segregating in the yellow fever mosquito Aedes aegypti L. (Diptera: Culicidae) population in Trinidad. The meiotic driver (M-D) is tightly linked to the male determining locus and selectively targets sensitive responders linked to the female determining allele, causing fragmentation of female gametes. This results in highly male-biased progeny. The M-D system was initially studied as a genetic tool for population control with limited success, but recently interest has focused on its potential for population replacement. This study examines the distribution and dynamics of the M-D system in Trinidad natural populations. We obtained ovitrap samples from seven geographically distinct regions and determined the allele frequencies of the driver (M-D) and sensitive (m(s)) versus insensitive (m(i)) responders, respectively. Frequencies of the M-D allele ranged from 0.1 to 0.5 and were low at the two major port cities, Port of Spain and San Fernando, suggesting the effects of frequent immigration by non-driving genotypes. Frequencies of the m(i) allele ranged from 0.4 to 0.7, suggesting the effects of strong selection by the driver. In addition, our results show that the driver and sensitivity of responders in the Trinidad populations are highly polymorphic. Continued studies of the dynamics of the M-D system in natural populations are critical to considerations of its use in population replacement.
Fitness effects of X chromosome drive in the stalk-eyed fly, Cyrtodiopsis dalmanni
4271Wilkinson, GSJ, P. M.; Kelleher, E. S.; Muscedere, M. L.; Lorsong, A., Journal of Evolutionary Biology, 19:1851-1860. 2006-01-09 00:00:00.
Sex-ratio (SR) males produce predominantly female progeny because most Y chromosome sperm are rendered nonfunctional. The resulting transmission advantage of X-SR chromosomes should eventually cause population extinction unless segregation distortion is masked by suppressors or balanced by selection. By screening male stalk-eyed flies, Cyrtodiopsis dalmanni, for brood sex ratio we found unique SR alleles at three X-linked microsatellite loci and used them to determine if SR persists as a balanced polymorphism. We found that X-SR/X-ST females produced more offspring than other genotypes and that SR males had lower sperm precedence and exhibited lower fertility when mating eight females in 24 h. Adult survival was independent of SR genotype but positively correlated with eye span. We infer that the SR polymorphism is likely maintained by a combination of weak overdominance for female fecundity and frequency dependent selection acting on male fertility. Our discovery of two SR haplotypes in the same population in a 10-year period further suggests that this SR polymorphism may be evolving rapidly.
Gene drive systems for insect disease vectors
4269Sinkins, SPG, F., Nature Reviews Genetics, 7:427-435. 2006-01-07 00:00:00.
The elegant mechanisms by which naturally occurring selfish genetic elements, such as transposable elements, meiotic drive genes, homing endonuclease genes and Wolbachia, spread at the expense of their hosts provide some of the most fascinating and remarkable subjects in evolutionary genetics. These elements also have enormous untapped potential to be used in the control of some of the world's most devastating diseases. Effective gene drive systems for spreading genes that can block the transmission of insect-borne pathogens are much needed. Here we explore the potential of natural gene drive systems and discuss the artificial constructs that could be envisaged for this purpose.
Male biased sex ratio in the Mediterranean fruit fly Ceratitis capitata, an example of Y-chromosome meiotic drive
4268Shahjahan, RMR, P. A.; Cook, L. M.; Wood, R. J., Heredity, 96:464-470. 2006-01-06 00:00:00.
A case of Y-chromosome meiotic drive is reported in the Mediterranean fruit fly Ceratitis capitata. It arose in an irradiated male and results in excess of males. Male excess is inherited strictly from father to son. A Y-linked factor MP (male producer) is proposed. Higher drive can be selected, but distortion declines rapidly in the absence of selection. Hybrid males from crosses between driving males and nondriving females also show drive but to a reduced extent, suggesting the action of suppressors. Sex ratio distortion is independent of postzygotic mortality, and is not associated with an obvious chromosome arrangement. Spermiogenesis in driving males is characterised by abnormalities in sperm tails and reduced numbers in some sperm cysts, whereas neighbouring cysts of the same MP testis are essentially wild type. The average number of missing sperms plus deformed sperms approximates to the average depression in female recovery among the progenies of siblings, suggesting that most of the missing or abnormal sperms would have given rise to females, that is, they would have been X-bearing. To explain the heterogeneity between neighbouring cysts, a theory is proposed that links it to variation in X-chromosome sensitivity to MP, arising by random suppression of the genetic basis of sensitivity during the six mitotic divisions in the origin of the cyst from its stem cell before meiosis.
Organization of the sex-ratio meiotic drive region in Drosophila simulans
4266Montchamp-Moreau, CO, D.; Chaminade, N.; Colard, A.; Aulard, S., Genetics, 174:1365-1371. 2006-01-04 00:00:00.
Sex-ratio meiotic drive is the preferential transmission of the X chromosome by XY males, which occurs in several Drosophila species and results in female-biased progeny. Although the trait has long been known to exist, its molecular basis remains completely unknown. Here we report a fine-mapping experiment designed to characterize the major drive locus on a sex-ratio X chromosome of Drosophila simulans originating from the Seychelles (X-SRG). This primary locus was found to contain two interacting elements at least, both of which are required for drive expression. One of them was genetically tracked to a tandem duplication containing six annotated genes (Trf2, CG32712, CG12125, CG1440, CG12123, org-1), and the other to a candidate region located similar to 110 kb away and spanning seven annotated genes. RT-PCR showed that all but two of these genes were expressed in the testis of both sex-ratio and standard males. In situ hybridization to polytene chromosomes revealed a complete association of the duplication with the sex-ratio trait in random samples of X chromosomes from Madagascar and Reunion.
Sex-ratio meiotic drive in Drosophila simulans: cellular mechanism, candidate genes and evolution
4265Montchamp-Moreau, C, Biochemical Society Transactions, 34:562-565. 2006-01-03 00:00:00.
The sex-ratio trait, reported in a dozen Drosophila species, is a type of naturally occurring meiotic drive in which the driving elements are located on the X chromosome. Typically, as the result of a shortage of Y bearing spermatozoa, males carrying a sex-ratio X chromosome produce a large excess of female offspring. The presence of sex-ratio chromosomes in a species can have considerable evolutionary consequences, because they can affect individual fitness and trigger extended intragenomic conflict. Here, I present the main results of the study performed in Drosophilosimulans. In this species, the loss of Y-bearing spermatozoa is related to the inability of the Y chromosome sister-chromatids to separate properly during meiosis II. Fine genetic mapping has shown that the primary sex-ratio locus on the X chromosome contains two distorter elements acting synergistically, both of which are required for drive expression. one element has been genetically mapped to a tandem duplication. To infer the natural history of the trait, the pattern of DNA sequence polymorphism in the surrounding chromosomal region is being analysed in natural populations of D. simulans harbouring sex-ratio X chromosomes. Initial results have revealed the recent spread of a distorter allele.
Transmission ratio distortion in the human body louse, Pediculus humanus (Insecta : Phthiraptera)
4264McMeniman, CJB, S. C., Heredity, 96:63-68. 2006-01-02 00:00:00.
We studied inheritance at three microsatellite loci in eight F-1 and two F-2 families of the body (clothes) louse of humans, Pediculus humanus. The alleles of heterozygous female-parents were always inherited in a Mendelian fashion in these families. Alleles from heterozygous male-parents, however, were inherited in two different ways: (i) in a Mendelian fashion and (ii) in a non-Mendelian fashion, where males passed to their offspring only one of their two alleles, that is, 100% nonrandom transmission. In male body lice, where there was non-Mendelian inheritance, the paternally inherited set of alleles was eliminated. We interpret this pattern of inheritance as evidence for extreme transmission ratio distortion of paternal alleles in this species.
Evidence of susceptibility and resistance to cryptic X-linked meiotic drive in natural populations of Drosophila melanogaster
4281Reed, FAR, R. G.; Aquadro, C. F., Evolution, 59:1280-1291. 2005-01-19 00:00:00.
There is mounting evidence consistent with a general role of positive selection acting on the Drosophila melanogaster X-chromosome. However, this positive selection need not necessarily arise from forces that are adaptive to the organism. Nonadaptive meiotic drive may exist on the X-chromosome and contribute to forces of selection. Females from a reference D. melanogaster line, containing the X-linked marker white, were crossed to males from 49 isofemale lines established from seven African and five non-African natural populations to detect naturally occurring meiotic drive. Several lines exhibited a departure from expected Mendelian transmission of X-chromosomes to the third generation (F-2) offspring, particularly those from hybrid African male parents. F2 viability was not correlated with skewed chromosomal inheritance. However, a significant difference in viability between cosmopolitan and tropical African crosses was observed. Recombination analysis supports the presence of a male-acting meiotic drive element near the centromeric region of the X-chromosome and putative recessive autosomal drive suppression. There is also evidence of another female-acting drive element linked to white. The possible role meiotic drive may contribute in shaping levels of genetic variation in D. melanogaster, and additional ways to test this hypothesis are discussed.
Genetic linkage between a sexually selected trait and X chromosome meiotic drive
4276Johns, PMW, L. L.; Wilkinson, G. S., Proceedings of the Royal Society B-Biological Sciences, 272:2097-2103. 2005-01-14 00:00:00.
Previous studies on the stalk-eyed fly, Cyrtodiopsis dalmanni, have shown that males with long eye-stalks win contests and are preferred by females, and artificial selection on male relative eye span alters brood sex-ratios. Subsequent theory proposes that X-linked meiotic drive can catalyse the evolution of mate preferences when drive is linked to ornament genes. Here we test this prediction by mapping meiotic drive and quantitative trait loci (QTL) for eye span. To map QTL we genotyped 24 microsatellite loci using 1228 F2 flies from two crosses between lines selected for long or short eye span. The crosses differed by presence or absence of a drive X chromosome, X-D, in the parental male. Linkage analysis reveals that X-D dramatically reduces recombination between X and X-D chromosomes. In the X-D cross, half of the F2 males carried the drive haplotype, produced partially elongated spermatids and female-biased broods, and had shorter eye span. The largest QTL mapped 1.3 cM from drive on the X chromosome and explained 36% of the variation in male eye span while another QTL mapped to an autosomal region that suppresses drive. These results indicate that selfish genetic elements that distort the sex-ratio can influence the evolution of exaggerated traits.
Gene drive systems in mosquitoes: rules of the road
4275James, AA, Trends in Parasitology, 21:64-67. 2005-01-13 00:00:00.
Population replacement strategies for controlling transmission of mosquito-borne diseases call for the introgression of antipathogen effector genes into vector populations. It is anticipated that these genes, if present at high enough frequencies, will impede transmission of the target pathogens and result in reduced human morbidity and mortality. Recent laboratory successes in the development of virus- and protozoan-resistant mosquito strains make urgent research of gene drive systems capable of moving effector genes into wild populations. A systematic approach to developing safe and effective gene drive systems that includes defining the requirements of the system, identifying naturally occurring or synthetic genetic mechanisms for gene spread upon which drive systems can be based and the successful adaptation of a mechanism to a drive system, should mitigate concerns about using genetically engineered mosquitoes for disease control.
TSETSE GENETICS: Contributions to Biology, Systematics, and Control of Tsetse Flies
26199R. H. Gooding and E. S. Krafsur, Annual Review of Entomology, 50:101-123. 2005-01-01 14:04:26.
Tsetse flies (Diptera: Glossinidae) constitute a small, ancient taxon of exclusively hematophagous insects that reproduce slowly and viviparously. Because tsetse flies are the only vectors of pathogenic African trypanosomes, they are a potent and constant threat to humans and livestock over much of sub-Saharan Africa. Despite their low fecundity, tsetse flies demonstrate great resilience, which makes population suppression expensive, transient, and beyond the capacities of private and public sectors to accomplish, except over small areas. Nevertheless, control measures that include genetic methods are under consideration at national and supranational levels. There is a pressing need for sufficient laboratory cultures of tsetse flies and financial support to carry out genetic research. Here we review tsetse genetics from organismal and population points of view and identify some research needs.
Evolution of autosomal suppression of the sex-ratio trait in Drosophila
4302Vaz, SCC, A. B., Genetics, 166:265-277. 2004-01-20 00:00:00.
The sex-ratio trait is the production of female-biased progenies due to X-linked meiotic drive in males of several Drosophila species. The driving X chromosome (called SR) is not fixed due to at least two stabilizing factors: natural selection (favoring ST, the nondriving standard X) and drive suppression by either Y-linked or autosomal genes. The evolution of autosomal suppression is explained by Fisher's principle, a mechanism of natural selectin that leads to equal proportion of males and females in a sexually reproducing population. In fact, sex-ratio expression is partially suppressed by autosomal genes in at least three Drosophila species. The population genetics of this system is not completely understood. In this article we develop a mathematical model for the evolution of autosomal suppressors of SR (sup alleles) and show that: (i) an autosomal suppressor cannot invade when SR is very deleterious in males (c < 1/3, where c is the fitness of SR/Y males); (ii) "SR/ST, sup/+" polymorphisms occur when SR is partially deleterious (similar to0.3 < c < 1); while (iii) SR neutrality (c = 1) results in sup fixation and thus in total abolishment of drive. So, surprisingly, as long as there is any selection against SR/Y males, neutral autosomal suppressors will not be fixed. In that case, when a polymorphic equilibrium exists, the average female proportion in SR/Y males' progeny is given approximately by (ac + 1 - a + roota(9) ( c + 1 )(2) + 1 - 4ac)/4ac, where a is the fitness of SR/ST females.
Reinvestigation of an endogenous meiotic drive system in the mosquito, Aedes aegypti (Diptera : Culicidae)
4295Mori, AC, D. D.; Graham, D. H.; Severson, D. W., Journal of Medical Entomology, 41:1027-1033. 2004-01-13 00:00:00.
We have initiated efforts to determine the molecular basis for the M-D meiotic drive system in the mosquito, Aedes aegypti. The effect of the M-D gene is a highly male-biased sex ratio, but varies depending on the frequency and sensitivity of a susceptible responder m(s) allele. The M-D system has potential as a mechanism for driving trangenes for pathogen resistance into natural Ae. aegypti populations. Because all previously existing laboratory strains carrying the M-D gene have been lost, we have selected for a new strain, T37, that carries a strong driver. Matings between T37 males and drive-susceptible in m(s) females result in progeny with highly biased sex ratios, wherein only approximate to14.7% females are produced. We discuss the potential for identifying M-D candidate genes based on comparisons with the well-described Drosophila melanogaster segregation distorter (SD) meiotic drive system and considerations for release of transgenic Ae. aegypti into natural populations where M-D and insensitive m(i) alleles are likely segregating.
Mapping of paternal-sex-ratio deletion chromosomes localizes multiple regions involved in expression and transmission
4294McAllister, BFB, L. W.; Werren, J. H., Heredity, 92:5-13. 2004-01-12 00:00:00.
The paternal-sex-ratio (PSR) chromosome in the parasitic wasp Nasonia vitripennis is a submetacentric supernumerary (B chromosome). Males transmit PSR, but after fertilization it causes the loss of the paternal autosomes. Paternal genome loss caused by PSR results in the conversion of a female (diploid) zygote into a male (haploid) under haplodiploid sex determination. In this study, site-specific markers were developed to assay deletion derivatives of PSR. Both polymerase chain reaction and Southern hybridization were used to detect the presence/absence of 16 single-site markers on a set of 20 functional and nine nonfunctional deletion chromosomes. Based on the pattern of marker loss on the deletion chromosomes, the basic organization of PSR was revealed. Two sets of markers were deleted independently, apparently representing the two arms of the submetacentric chromosome. The presence or absence of specific regions was examined in relation to phenotypic characteristics of the deletion chromosomes; ability to cause paternal genome loss, and stability in mitotic cell divisions. Rather than identifying a single region on PSR as being responsible for PSR function, the results suggest that the retention of one of two chromosomal regions is sufficient for causing paternal genome loss. Furthermore, a region was identified that is tightly correlated with mitotic stability, as measured from chromosomal transmission rates. Functional chromosomes with short-arm deletions had high (similar to100%) transmission rates, whereas functional chromosomes with long-arm deletions had low (similar to85%) transmission rates.
B chromosomes in Sternorrhyncha (Hemiptera, Insecta)
4293Maryanska-Nadachowska, A, Cytogenetic and Genome Research, 106:210-214. 2004-01-11 00:00:00.
In the hemipteroid insects of the suborder Sternorrhyncha, B chromosomes are relatively common in comparison with other suborders of Hemiptera. However, the occurrence of supernumerary chromosomes is restricted, in most cases, to several genera or closely related species. At least in some species of Psylloidea with the XY sex determination system, a mitotically stable B chromosome integrated into an achiasmatic segregation system with the X, and became fixed as a Y chromosome. In some Aphidoidea with a multiple X system of sex determination, B chromosomes appear to be in fact non-functional X chromosomes. Supernumerary chromosomes thus probably play an important role in the evolution of sex determination systems in Sternorrhyncha. Copyright (C) 2004 S. Karger AG, Basel.
Identification of quantitative trait loci affecting sex determination in the eastern treehole mosquito (Ochlerotatus triseriatus)
4290Graham, DHH, J. L.; Black, W. C., Journal of Heredity, 95:35-45. 2004-01-08 00:00:00.
Laboratory colonies of the eastern treehole mosquito (Ochlerotatus triseriatus (Say)) exhibit a consistent female-biased sex ratio. This is unusual among mosquito species, in which heritable sex ratio distortion is usually male biased and mediated by meiotic drive. Quantitative trait loci (QTL) affecting sex were mapped in an F-1 intercross to better understand the genetics underlying this female bias. In P-1 and F-1 parents and in 146 F-2 individuals with a female-biased sex ratio (106 females:40 males), regions of seven cDNA loci were analyzed with single-strand conformation polymorphism (SSCP) analysis to identify and orient linkage groups. Genotypes were also scored at 73 random amplified polymorphic DNA (RAPD)-SSCP loci. In addition to the sex locus, at least four QTL affecting sex determination were detected with interval mapping on linkage groups I and II. Alleles at the sex locus cumulatively accounted for approximately 61-77% of the genetic variance in sex. Alleles at QTL adjacent to the sex locus and at a QTL on the opposite end of linkage group I increased the proportion of females, but alleles at a QTL on linkage group I and a second QTL on linkage group II increased the proportion of males. The female-biased sex ratio observed in laboratory colonies of O. triseriatus is most easily explained by the existence of multiple female biased distorter loci, as have been observed in other Diptera.
Sperm survival in female stalk-eyed flies depends on seminal fluid and meiotic drive
4289Fry, CLW, G. S., Evolution, 58:1622-1626. 2004-01-07 00:00:00.
Sperm competition is common in many insect species; however, the mechanisms underlying differences in sperm precedence are not well understood. In the stalk-eyed fly, Cyrtodiopsis whitei (Diptera, Diopsidae), sperm precedence is influenced by the presence of sex chromosome meiotic drive. When drive-carrying males compete with non-driving males for fertilizations within a female, the number of progeny sired by drive males is significantly fewer than predicted by sperm mixing alone. Thus, drive males apparently suffer not only a reduction in the number of viable sperm produced, but also a reduction in sperm competitive ability. In this study, we manipulated the amount and source of seminal fluid and sperm received by females by interrupting copulations before sperm, but after seminal fluid, was transferred. We find that seminal fluid from another male influences the number of progeny sired by a drive-carrying male when both males mate with the same female. Sperm viability staining reveals that sperm from drive males are incapacitated by seminal fluid from other males within the female reproductive tract. These results suggest that multiple mating by females enables seminal fluid products to interact differentially with sperm and may reduce the transmission advantage of the drive chromosome.
Persistence of an extreme sex-ratio bias in a natural population
4287Dyson, EAH, G. D. D., Proceedings of the National Academy of Sciences of the United States of America, 101:6520-6523. 2004-01-05 00:00:00.
The sex ratio is a key parameter in the evolution and ecology of a species. Selfish genetic elements that bias the sex ratio of affected individuals are well known and characterized, but their effect on populations has been considered limited, because either the element does not achieve high prevalence or the host rapidly evolves resistance to the distorting element, reducing its prevalence. We tested whether the host necessarily prevails by using a butterfly system where records from the early part of the 20th century reported extreme sex-ratio bias in nature. We reexamined this population and found the bias was present today, 400 generations after the original record, with a population sex ratio of 100 females per male. The sex-ratio bias was associated with the presence of a heritable male-killing Wolbachia infection in 99% of adult females, against which the host butterfly has failed to evolve resistance. The resultant dearth of males causes an average 57% reduction in the reproductive output of adult females. Persistence of the population despite the very high frequency of the sex-ratio distorter appears to be associated with the ability of males to mate >50 times in their life combined with a high intrinsic rate of increase of the species.
Inverted meiosis and meiotic drive in mealybugs
4285Bongiorni, SF, P.; Pippoletti, D.; Prantera, G., Chromosoma, 112:331-341. 2004-01-03 00:00:00.
In the males of lecanoid coccids, or mealybugs, an entire, paternally derived, haploid chromosome set becomes heterochromatic after the seventh embryonic mitotic cycle. In females, both haploid sets are euchromatic throughout the life cycle. In mealybugs, as in all homopteran species, chromosomes are holocentric. Holocentric chromosomes are characterized by the lack of a localized centromere and consequently of a localized kinetic activity. In monocentric species, sister chromatid cohesion and monopolar attachment play a pivotal role in regulating chromosome behavior during the two meiotic divisions. Both these processes rely upon the presence of a single, localized centromere and as such cannot be properly executed by holocentric chromosomes. Here we furnish further evidence that meiosis is inverted in both sexes of mealybugs and we suggest how this might represent an adaptation to chromosome holocentrism. Moreover, we reveal that at the second meiotic division in males a monopolar spindle is formed, to which only euchromatic chromosomes become attached. By this mechanism the paternally derived, heterochromatic, haploid chromosome set strictly segregates from the euchromatic one, and it is then excluded from the genetic continuum as a result of meiotic drive.
The B chromosome polymorphism of the grasshopper Eyprepocnemis plorans in North Africa. IV. Transmission of rare B chromosome variants
4284Bakkali, MC, J. P. M., Cytogenetic and Genome Research, 106:332-337. 2004-01-02 00:00:00.
In addition to the principal B chromosome (B-1) in Moroccan populations of the grasshopper Eyprepocnemis plorans, nine B chromosome variants appeared at low frequency. The transmission of five of these rare B chromosome variants through females was analysed in three natural populations. Sixteen controlled crosses provided useful information on the transmission of B-M2, B-M6 and B-M7 in Smir, B-M3 and B-M6 in SO. DE. A. (Societe de Developpement Agricole lands near Ksar-el-Kebir city), and B-M2 and BM10 in Mechra, all located in Morocco. Since six female parents carried two different B variants, a total of 22 progeny analyses could be studied. Intraindividual variation in B transmission rate (k(B)) was observed among the successive egg pods in 26.7% of the females, but this variation did not show a consistent temporal pattern. Only the B-M2 and B-M6 variants in Smir showed net drive, although variation was high among crosses, especially for B-M2. These two variants are thus good candidates for future regenerations ( the replacement of a neutralized B, B-1 in this case, by a new driving variant, B-M2 or B-M6) in Smir, the northern population where the B polymorphism is presumably older. The analysis of all crosses performed in the three populations, including those reported previously for the analysis of B-1 transmission, showed that the largest variance in k(B) among crosses stands at the individual level, and not at population or type of B levels. The implications of these findings for the occurrence of possible regeneration processes in Moroccan populations are discussed. Copyright (C) 2004 S. Karger AG, Basel.
Genetic dissection of hybrid incompatibilities between Drosophila simulans and D-mauritiana. III. Heterogeneous accumulation of hybrid incompatibilities, degree of dominance, and implications for Haldane’s rule
4317Tao, YH, D. L., Evolution, 57:2580-2598. 2003-01-15 00:00:00.
The genetic basis of Haldane's rule was investigated through estimating the accumulation of hybrid incompatibilities between Drosophila simulans and D. mauritiana by means of introgression. The accumulation of hybrid male sterility (HMS) is at least 10 times greater than that of hybrid female sterility (HFS) or hybrid lethality (HL). The degree of dominance for HMS and HL in a pure D. simulans background is estimated as 0.23-0.29 and 0.33-0.39, respectively; that for HL in an F-1 background is unlikely to be very small. Evidence obtained here was used to test the Turelli-Orr model of Haldane's rule. Composite causes, especially, faster-male evolution and recessive hybrid incompatibilities, underlie Haldane's rule in heterogametic male taxa such as Drosophila (XY male and XX female). However, if faster-male evolution is driven by sexual selection, it contradicts Haldane's rule for sterility in heterogametic-female taxa such as Lepidoptera (ZW female and ZZ male). The hypothesis of a faster-heterogametic-sex evolution seems to fit the current data best. This hypothesis states that gametogenesis in the heterogametic sex, instead of in males per se, evolves much faster than in the homogametic sex, in part because of sex-ratio selection. This hypothesis not only explains Haldane's rule in a simple way, but also suggests that genomic conflicts play a major role in evolution and speciation.
Closing the (Ran)GAP on segregation distortion in Drosophila
4313Kusano, AS, C.; Chan, H. Y. E.; Ganetzky, B., Bioessays, 25:108-115. 2003-01-11 00:00:00.
Segregation Distorter (SD) is a meiotic drive system in Drosophila that causes preferential transmission of the SD chromosome from SD/SD+ males owing to induced dysfunction of SD+ spermatids. Since its discovery in 1956, SD and its mode of action have baffled biologists. Recently, substantial progress has been made in elucidating this puzzle. Sd, the primary gene responsible for distortion encodes a mutant RanGAP, a key protein in the Ran signaling pathway required for nuclear transport and other nuclear functions. The mutant protein is enzymatically active but mislocalized to nuclei, which apparently disrupts Ran signaling by reducing intranuclear Ran-GTP levels. Some evidence suggests that a defect in nuclear transport may be the main cause of sperm dysfunction. Although important questions remain, the basic mechanism of distortion is now understood sufficiently well that specific hypotheses can be formulated and tested. This previously mysterious genetic system may now offer unique insights into novel aspects of regulation by Ran. (C) 2003 Wiley Periodicals, Inc.
Responder (Rsp) alleles in the Segregation Distorter (SD) system of meiotic drive in Drosophila may represent a complex family of satellite repeat sequences
4311Houtchens, KL, T. W., Genetica, 117:291-302. 2003-01-09 00:00:00.
In D. melanogaster males carrying Segregation Distorter (SD) second chromosomes, sperm receiving sensitive alleles of the Responder (Rsp) locus are subject to high rates of dysfunction. The Rsp region is located in 2R immediately adjacent to the centromere in heterochromatic band 39, and covers roughly 600 kb of material, of which approximately 85 kb is comprised of several hundred copies of a 240-bp satellite DNA sequence. Cytological observations as well as molecular analysis of rearrangements which bisect h39 indicate that sensitivity of the Rsp target to SD action is also subdivisible, and sensitivities of the component pieces appear to be correlated with copy number of the 240 bp repeat. In an attempt to examine possible higher order sequence structure for these blocks, PCR using single primers derived from a canonical repeat was used to identify potential reversals of direction of tandem arrays; that is, head-to-head or tail-to-tail junctions. Surprisingly, for two different Rsp alleles, only a single such reversal product for each was identified, differing in size and sequence between alleles. Sequencing of PCR products identified diverged copies of the canonical repeats that would not have been found using the levels of DNA stringency employed in earlier studies. Examination of Southern digests and slot-blots for DNA quantification indicates that adding the estimated numbers of such diverged copies to the canonical repeat copies discovered earlier is potentially sufficient to account for the entire 600 kb Rsp region. This adds strength to the hypothesis that this extended family of repeats is in fact the target of SD-mediated sperm dysfunction. Implications of these results for understanding the evolution of repetitive DNA are also discussed.
Does Stellate cause meiotic drive in Drosophila melanogaster?
4320Belloni, MT, P.; Bozzetti, M. P.; Palumbo, G.; Robbins, L. G., Genetics, 161:1551-1559. 2002-01-18 00:00:00.
Drosophila melanogaster males deficient for the crystal (cry) locus of the Y chromosome that carry between 15 and 60 copies of the X-linked Stellate (Ste) gene are semisterile, have elevated levels of nondisjunction, produce distorted sperm genotype ratios (meiotic drive), and evince hyperactive transcription of Ste in the testes. Ste seems to be the active element in this system, and it has been proposed that the ancestral Ste gene was "selfish" and increased in frequency because it caused meiotic drive. This hypothetical evolutionary history is based on the idea that Ste overexpression, and not the lack of cry, causes the meiotic drive of cry(-) males. To test whether this is true, we have constructed a Ste-deleted X chromosome and examined the phenotype of Ste(-)/cry(-) males. If hyperactivity of Ste were necessary for the transmission defects seen in cry- males, cry males completely deficient for.Ste would be normal. Although it is impossible to construct a completely Ste(-) genotype, we find that Ste(-)/cry(-) males have exactly the same phenotype as Ste(+)/cry(-) males. The deletion of all X chromosome Ste copies not only does not eliminate meiotic drive and nondisjunction, but it also does not even reduce them below the levels produced when the X carries 15 copies of Ste.
Sex-ratio drive in Drosophila simulans: Variation in segregation ratio of X chromosomes from a natural population
4325Montchamp-Moreau, CC, M., Genetics, 162:1221-1231. 2002-01-03 00:00:00.
The sex-ratio trait that exists in a dozen Drosophila species is a case of naturally occurring X chromosome drive that causes males to produce female-biased progeny. Autosomal and Y polymorphism for suppressors are known to cause variation in drive expression, but the X chromosome polymorphism has never been thoroughly investigated. We characterized 41 X chromosomes from a natural population of Drosophila simulans that had been transferred to a suppressor-free genetic background. We found two clear-cut groups of chromosomes, sex-ratio and standard. The sex-ratio X chromosomes differed in their segregation ratio (81-96% females in the progeny), the less powerful drivers being less stable in their expression. A sib analysis, using a moderate driver, indicated that within-X variation in drive expression depended on genetic (autosomal) or epigenetic factors and that the age of the males also affected the trait. The other X chromosomes produced equal or roughly equal sex ratios, but again with significant variation. The continuous pattern of variation observed within both groups suggested that, in addition to a major sex-ratio gene, many X-linked loci of small effect modify the segregation ratio of this chromosome and are maintained in a polymorphic state. This was also supported by the frequency distribution of sex ratios produced by recombinant X chromosomes.
Segregation distortion induced by wild-type RanGAP in Drosophila
4324Kusano, AS, C.; Ganetzky, B., Proceedings of the National Academy of Sciences of the United States of America, 99:6866-6870. 2002-01-02 00:00:00.
Segregation Distorter (SD) is a meiotic drive system in Drosophila that causes preferential transmission of the SD chromosome from SD/SD+ males owing to the induced dysfunction of SD+ spermatids. The key distorter locus, Sid, is a dominant neomorphic allele encoding a truncated, but enzymatically active, RanGAP (RanGTPase-activating protein) whose nuclear mislocalization underlies distortion by disrupting the Ran signaling pathway. Here, we show that even wild-type RanGAP can cause segregation distortion when it is overexpressed in the male germ line or when the gene dosage of a particular modifier locus is increased. Both manipulations result in substantial nuclear accumulation of RanGAP. Distortion can be suppressed by overexpression of Ran or Ran guanine nucleotide exchange factor (RanGEF) in the male germ line, indicating that the primary consequence of nuclear mislocalization of RanGAP is reduction of intranuclear RanGTP levels. These results prove that segregation distortion does not depend on any unique properties of the mutant RanGAP encoded by Sid and provide a unifying explanation for the occurrence of distortion in a variety of experimental situations.
Sperm development, age and sex chromosome meiotic drive in the stalk-eyed fly, Cyrtodiopsis whitei
4337Wilkinson, GSS, M. I., Heredity, 87:17-24. 2001-01-15 00:00:00.
The cytological basis of X chromosome meiotic drive or sex ratio (SR) has been reported for several species of Drosophila but not for other species. Here we describe how sperm development in the stalk-eyed fly, Cyrtodiopsis whitei, influences progeny sex proportion, in order to determine if a common developmental mechanism could cause meiotic drive in these distantly related taxa. Because age has been found to affect the degree of segregation distortion in some Drosophila, we tested flies from six to 26 weeks of age. We find that spermatocyst bundles in SR males frequently contain incompletely elongated spermatid nuclei independently of male age. Older males have, however, more spermatocyst bundles in their testes than younger males. Abnormal spermatid elongation affects male fertility since SR males produce 74% as many progeny per week as ST males. The proportion of spermatocyst bundles with improperly elongated spermatid nuclei explains 71% of the variation in progeny sex proportion. After reviewing the literature on sperm development and meiotic drive, we conclude that the cytological basis of meiotic drive in diopsids closely resembles Drosophila. Across species in both groups, the production of fertile males is associated with less than half of all spermatids not elongating normally in a spermatocyst bundle. We discuss the possibility that frequency-dependent selection on male fertility could stabilize the drive polymorphism in these unusual flies.
Meiotic drive alters sperm competitive ability in stalk-eyed flies
4336Wilkinson, GSF, C. L., Proceedings of the Royal Society B-Biological Sciences, 268:2559-2564. 2001-01-14 00:00:00.
Meiotic drive results when sperm carrying a driving chromosome preferentially survive development. Meiotic drive should therefore influence sperm competition because drive males produce fewer sperm than non-drive males. Whether meiotic drive also influences the competitive ability of sperm after ejaculation is unknown. Here we report the results from reciprocal crosses that are designed for estimating the sperm precedence of male stalk-eyed flies (Cyrtodiopsis whitei) with or without X-linked meiotic drive. We find that nearly half of all sex-ratio males, as compared with 14 % of non-sex-ratio males, fail to produce young in a reciprocal cross. Furthermore, the proportion of progeny sired by a sex-ratio male in a female jointly inseminated by a non-sex-ratio male was less than expected from the number of sperm transferred. These effects are not due to differential sperm storage by females because, after a single mating with a sex-ratio male, all females stored sperm and because two sex-ratio males share paternity after jointly mating with a female. In addition to demonstrating a new mechanism of sperm competition, these results provide insight into the maintenance of sex-ratio polymorphisms. Sex-ratio males have less than one-half the fertility of non-sex-ratio males, as is required in order for frequency-dependent selection on males to produce a stable sex-ratio polymorphism.
Sex-ratio segregation distortion associated with reproductive isolation in Drosophila
4333Tao, YH, D. L.; Laurie, C. C., Proceedings of the National Academy of Sciences of the United States of America, 98:13183-13188. 2001-01-11 00:00:00.
Sex-ratio distortion is the most common form of non-Mendelian segregation observed in natural populations. It may occur even more frequently than direct observations suggest, because the dysgenic population consequences of a biased sex ratio are expected to result in the rapid evolution of suppressors, resulting in suppressed or "cryptic" segregation distortion. Here we report evidence for cryptic sex-ratio distortion that was discovered by introgressing segments of the genome of Drosophila mauritiana into the genome of Drosophila simulans. The autosomal suppressor of sex-ratio distortion, which is also associated with a reduction in hybrid male fertility, has been genetically localized to a region smaller than 80-kb pairs in chromosome 3.
Success in Zanzibar: Eradication of tsetse
27123A. R. Msangi, N. Kiwia, I. I. Malele, F. Mramba, K. M. Saleh, W. A. Mussa, K. G. Juma, V. A. Dyck, M. J. B. Vreysen, A. G. Parker, U. Feldmann, Z. R. Zhu and H. Pan, Area-Wide Control of Fruit Flies and Other Insect Pests, 2000-06-06 13:17:29.
There are about 22 species of tsetse flies found nowhere else in the world except in 36 countries of sub-Saharan Africa Tsetse flies transmit a debilitating and often fatal disease, trypanosomosis, which causes tremendous losses of livestock, and severely limits agricultural production (it reduces output of milk and meat, causes mortality, infertility and abortion in livestock, deprives the rural population of draught power and manure to improve and increase crop production) Tsetse flies also transmit human trypanosomosis, commonly known as 'sleeping sickness' It is estimated that over 55 million people living in rural sub-Saharan Africa are at risk from this fatal disease Tanzania's Zanzibar Island is situated 35 km off the eastern coast and comprises two main islands, Unguja and Pemba Previous surveys revealed that out of the seven tsetse species found on mainland Tanzania, only Glossina austeni Newstead infested Unguja Island No tsetse fly was found on the island of Pemba The fly is responsible for the cyclical transmission of trypanosomosis in livestock, the causative agents being mainly Trypanosoma congolense and, to a lesser extent, T vivax It is estimated that in Zanzibar, the disease causes annual losses of US$2 million Since fly suppression by conventional techniques has often resulted in short-term success, Tanzania has always appreciated that the long-term solution to the trypanosomosis problem is the eradication of tsetse flies in the country In 1994, the International Atomic Energy Agency (IAEA) and the United Republic of Tanzania embarked on a project with the objective of eradicating tsetse flies from Zanzibar Island by applying the sterile insect technique (SIT) (Dyck et al 1995, in press) Previous tsetse eradication efforts in Tanzania using SIT, enabled the establishment of a modest capacity on tsetse mass rearing in Tanga (Williamson et al 1983) The Zanzibar tsetse project was successfully completed in 1997 The estimated cost was US$7,941,000 but only US$5,788,097 was actually spent Financial assistance came from international donors such as the governments of Belgium, Canada, China, Sweden, the UK and the USA The results and achievements of the Zanzibar tsetse fly eradication project are presented in this paper
Glossina austeni (Diptera: Glossinidae) Eradicated on the Island of Unguja, Zanzibar, Using the Sterile Insect Technique
27121M. J. B. Vreysen, K. M. Saleh, M. Y. Ali, A. M. Abdulla, Z.-R. Zhu, K. G. Juma, V. A. Dyck, A. R. Msangi, P. A. Mkonyi and H. U. Feldmann, Journal of Economic Entomology, 123-135. 2000-02-01 12:59:17.
An area-wide integrated tsetse eradication project was initiated in Zanzibar in 1994 by the International Atomic Energy Agency and the governments of Tanzania and Zanzibar, to eradicate Glossina austeni Newstead from Unguja Island (Zanzibar) using the sterile insect technique. Suppression of the tsetse population on Unguja was initiated in 1988 by applying residual pyrethroids as a pour-on formulation to livestock and by the deployment of insecticide impregnated screens in some of the forested areas. This was followed by sequential releases of gamma-sterilized male flies by light aircraft. The flies, packaged in carton release containers, were dispersed twice a week along specific flight lines separated by a distance of 1–2 km. More than 8.5 million sterile male flies were released by air from August 1994 to December 1997. A sterile to indigenous male ratio of >50:1 was obtained in mid-1995 and it increased to >100:1 by the end of 1995. As a consequence the proportion of sampled young females (1–2 ovulations), with an egg in utero in embryonic arrest or an uterus empty as a result of expulsion of a dead embryo, increased from <25% in the 1st quarter to >70% in the last quarter of 1995. In addition, the age structure of the female population became significantly distorted in favor of old flies (≥4 ovulations) by the end of 1995. The apparent density of the indigenous fly population declined rapidly in the last quarter of 1995, followed by a population crash in the beginning of 1996. The last trapped indigenous male and female flies were found in weeks 32 and 36, 1996, respectively. Time for 6 fly generations elapsed between the last catch of an indigenous fly and the end of the sterile male releases in December 1997.
Non-Mendelian segregation of sex chromosomes in heterospecific Drosophila males
4341Dermitzakis, ETM, J. P.; Waldrip, H. M.; Clark, A. G., Genetics, 154:687-694. 2000-01-19 00:00:00.
Interspecific hybrids and backcrossed organisms generally suffer from reduced viability and/or fertility. To identify and genetically map these defects, we introgressed regions of the Drosophila sechellia genome into the D. simulans genome. A female-biased sex ratio was observed in 24 of the 221 recombinant inbred lines, and subsequent tests attributed the skew to failure of Y-bearing sperm to fertilize the eggs. Apparently these introgressed lines fail to suppl ess a normally silent meiotic drive system. Using molecular markers we mapped two regions of the Drosophila genome that appear to exhibit differences between D. simulans and D. sechellia in their regulation of sex chromosome segregation distortion. The data indicate that the sex ratio phenotype results from an epistatic interaction between at least two factors. We discuss whether this observation is relevant to the meiotic drive theory of hybrid male sterility.
Sex-ratio meiotic drive in Drosophila simulans is related to equational nondisjunction of the Y chromosome
4338Cazemajor, MJ, D.; Montchamp-Moreau, C., Genetics, 154:229-236. 2000-01-16 00:00:00.
The sex-ratio trait, an example of naturally occurring X-linked meiotic drive, has been reported in a dozen Drosophila species. Males carrying a sex-ratio X chromosome produce an excess of female offspring caused by a deficiency of Y-bearing sperm. In Drosophila simulans, such males produce similar to 70-90% female offspring, and 15-30% of the male offspring are sterile. Here, we investigate the cytological basis of the drive in this species. We show that the sex-ratio trait is associated with nondisjunction of Y chromatids in meiosis II. Fluorescence in situ hybridization (FISH) using sex-chromosome-specific probes provides dir-ect evidence that the drive is caused by the failure of the resulting spermatids to develop into functional sperm. XYY progeny were not observed, indicating that few or no YY spermatids escape failure. The recovery of XO males among the progeny of sex-ratio males shows that some nullo-XY spermatids become functional sperm and likely explains the male sterility. A review of the cytological data. in other species shows that aberrant behavior of the Y chromosome may be a common basis of sex-ratio meiotic drive in Drosophila and the signal that triggers differential spermiogenesis failure.
Chromosomally-induced meiotic drive in Drosophila males: Checkpoint or fallout?
4347Tomkiel, JE, Genetica, 109:95-103. 2000-01-05 00:00:00.
In male Drosophila melanogaster, anomalies in sex chromosome pairing at meiosis often lead to complete or partial sperm dysfunction. This observation has led to the suggestion that defects in either the efficiency or configuration of chromosome pairing at metaphase trigger a checkpoint mechanism that leads to the elimination of meiotic products. Here, we discuss this model in consideration of recent observations on the conservation of metaphase checkpoint components in male meiosis, and on the phenotype of new alleles of the male-specific meiotic mutant teflon. Based on these observations, we propose an alternative hypothesis for the cause of sperm dysfunction in cases of chromosomal sterility and drive. We suggest that disruption of the prophase compartmentalization of sex chromatin, rather than abnormal pairing at metaphase, may be the causative defect. Such disruption may occur as a result of perturbations in sex chromosome pairing, or by translocations involving autosomal and sex chromatin. We discuss how this hypothesis may account for previously described examples chromosomal causes of meiotic drive and sterility in Drosophila.
A male-biased primary sex ratio and larval mortality in Eucheira socialis (Lepidoptera : Pieridae)
4363Underwood, DLAS, A. M., Evolutionary Ecology Research, 1:703-717. 1999-01-21 00:00:00.
We investigated the sex ratio and sex-biased mortality in the Mexican pierid butterfly, Eucheira socialis westwoodi. We studied two populations between 1990 and 1997 along Mexico Highway 40, which runs from Mazatlan, Sinaloa to Durango, Durango, Populations occurring between km 64 and 101 and between km 163 and 213 were designated 'eastern' and 'western', respectively We determined the primary sex ratio of egg masses from these populations in 1992, 1995, 1996 and 1997, The primary sex ratio varied from 68.0 to 75.5% male and from 63.7 to 79.3% male in the eastern and western populations, respectively. The frequency of significantly male-biased full sib groups was between 55 and 100% in the east and between 67 and 94% in the west. For all years, in both populations, the primary sex ratio was significantly different from 1:1. Lf the probability of a given zygote being male is the same across sibships, the distribution of the primary sex ratio should be binomial. For years where at least 10 egg masses were collected, the distribution of primary sex ratio was significantly different from a binomial in all years in the east and two of three years in the west. We studied larval and pupal mortality in these populations in 1990, 1991 and 1997. Larval mortality was consistently disproportionately male, varying from 83 to 100% male. Pupal mortality tended to be female-biased. The operational sex ratio varied from 65 to 71% male in the east and from 70 to 76% male in the west.
Genetic and molecular characterization of sting, a gene involved in crystal formation and meiotic drive in the male germ line of Drosophila melanogaster
4362Schmidt, AP, G.; Bozzetti, M. P.; Tritto, P.; Pimpinelli, S.; Schafer, U., Genetics, 151:749-760. 1999-01-20 00:00:00.
The sting mutation, caused by a P element inserted into polytene region 32D, was isolated by a screen for male sterile insertions in Drosophila melanogaster. This sterility is correlated with the presence of crystals in spermatocytes and spermatids that are structurally indistinguishable from those produced in males carrying a deficiency of the Y-linked crystal (cry) locus. In addition, their morphology is needle-like in Ste(+) flies and star-shaped in Ste flies, once again as observed in cry(-) males. The sti mutation leads to meiotic drive of the sex chromosomes, and the strength of the phenomenon is correlated with the copy number of the repetitive Ste locus. The same correlation is also true for the penetrance of the male sterile mutation. A presumptive sti null allele results in male sterility and lethal maternal effect. The gene was cloned and shown to code for a putative protein that is 866 amino acids long. A C-terminal domain of 52 amino acids is identified that is well conserved in proteins from different organisms. The gene is expressed only in the germline of both sexes. The interaction of sting with the Ste locus can also be demonstrated at the molecular level. While an unprocessed 8-kb Ste primary transcript is expressed in wild-type males, in X/Y-homoozygous sti males, as in X/Y cry(-) males, a 0.7-kb mRNA is produced.
Truncated RanGAP encoded by the Segregation Distorter locus of Drosophila
4359Merrill, CB, L.; Kusano, A.; Ganetzky, B., Science, 283:1742-1745. 1999-01-17 00:00:00.
Segregation Distorter (SD) in Drosophila melanogaster is a naturally occurring meiotic drive system in which the SD chromosome is transmitted from SD/SD+ males in vast: excess over its homolog owing to the induced dysfunction of SD+-bearing spermatids. The Sd Locus is the key distorting gene responsible for this phenotype. A genomic fragment from the Sd region conferred full distorting activity when introduced into the appropriate genetic background by germline transformation. The only functional product encoded by this fragment is a truncated version of the RanGAP nuclear transport protein. These results demonstrate that this mutant RanGAP is the functional Sd product.
Models of sex-ratio meiotic drive and sexual selection in stalk-eyed flies
4358Lande, RW, G. S., Genetics Research, 74:245-253. 1999-01-16 00:00:00.
Hypertrophied sexually dimorphic eye stalks have evolved independently in several families of Diptera, with the eyespan of males exceeding their total body length in some species. These structures function in intermale contests for territories and in mate attraction, the classical mechanisms of sexual selection. In the family Diopsidae, species with extremely exaggerated eye stalks and marked sexual dimorphism in relative eyespan also usually have strongly female-biased sex ratios in nature caused by X-linked meiotic drive, whereas species with relatively small eye stalks have little or no sexual dimorphism, often lack meiotic drive and have even sex ratios. We investigate the possible connection between sexual selection and sex-ratio meiotic drive by analysing a three-locus model for the evolution of female choice for a male character associated with meiotic drive. Both meiotic drive and the male character are X-linked and the female preference is autosomal. Our model shows that suppressed recombination between meiotic drive and the male character, e.g. by inversion of the X chromosome, is necessary for sex-ratio selection to promote the origin of female mating preferences and exaggerated secondary sexual characters. With complete suppression of recombination, sexual selection reduces the frequency of meiotic drive, and may eliminate it. Very rare recombination, gene conversion or mutation, at rates characteristic of chromosome inversions in Drosophila, restores the meiotic drive polymorphism to its original equilibrium. Sex-ratio meiotic drive may thus act as a catalyst accelerating the origin of female mating preference and exaggerated male traits.
How common are meiotically driving sex chromosomes in insects?
4357Jiggins, FMH, G. D. D.; Majerus, M. E. N., American Naturalist, 154:481-483. 1999-01-15 00:00:00.
In summary, we argue that the hypothesis that sex chromosome; meiotic drive is common within the insects is in; fact not proved. We feel that, although it is unlikely that; it will be found exclusively in the Diptera, there is a case; to be made that the Diptera are a hot spot for the occurrence; of sex chromosome meiotic drive. Further research; is clearly necessary to clarify this point. If the Diptera; are found to be different, then we must ask why this; is so. Meiotic drive often involves the destruction of gametes; that do not bear the drive allele causing a reduction; in the number of functional gametes. This may mean that; meiotically driving sex chromosomes are unlikely to spread; in female heterogametic taxa such as the Lepidoptera because; a reduction in the number of eggs is more costly; than a reduction in the number of sperm. Among male; heterogametic taxa, it is unclear what could make Dipteran; meiosis special.
Suppression of sex-ratio meiotic drive and the maintenance of Y-chromosome polymorphism in Drosophila
4356Jaenike, J, Evolution, 53:164-174. 1999-01-14 00:00:00.
Like several other species of Drosophila, D. quinaria is polymorphic for X-chromosome meiotic drive; matings involving males that carry a "sex-ratio" X chromosome (X(SR)) result in the production of strongly female-biased offspring sex ratios (Jaenike 1996). A survey of isofemale lines of D, quinaria from several populations reveals that there is genetic variation for partial suppression of this meiotic drive. Crossing experiments show that there is Y-linked. and probably autosomal, variation for suppression of drive. Y-linked suppressors of X-chromosome drive have now been described in several species of Diptera. I develop a simple model for the maintenance of Y-chromosome polymorphism in species polymorphic for X-linked meiotic drive. One interesting feature of this model is that, if there is a stable Y-chromosome polymorphism, then the equilibrium frequency of the standard and sex-ratio X chromosomes is determined solely by Y-chromosome parameters, not by the fitness effects of the different X chromosomes on their carriers. This model suggests that Y-chromosome polymorphism may be easier to maintain than previously thought, and I hypothesize that karyotypic variation in Y chromosomes will be found to be associated with suppression of sex-ratio meiotic drive in other species of Drosophila.
Are Drosophila SR drive chromosomes always balanced?
4351Carvalho, ABV, S. C., Heredity, 83:221-228. 1999-01-09 00:00:00.
SR chromosomes are the best-known case of sex chromosome meiotic drive. These X chromosomes cause the production of female-biased progenies in several Drosophila species; Due to their meiotic drive advantage, they are expected to spread and become fixed, resulting in population extinction due to the lack of males. However, this apparently does not occur: SR chromosomes are maintained in balanced polymorphisms, resulting from the equilibrium between their meiotic drive advantage and deleterious fitness effects. In this paper we review the current explanations for their deleterious effects and we argue that it is highly improbable that all newly emerged SR are sufficiently deleterious to avoid fixation. Unbalanced SR almost certainly arise and go unnoticed because of three possible outcomes: (i) fixation followed by extinction of the population or species; (ii) fixation followed by the emergence and fixation of drive suppressors, restoring the normal 1:1 sexual proportion; or (iii) transformation into balanced SR due to partial suppression. If these outcomes really occur, then extant cases of sex-chromosome meiotic drive such as SR, causing small deviations on the population sexual proportion are only the tip of the iceberg and strong sexual proportion shifts (possibly followed by extinction) are a more common feature of species evolution than is usually assumed.
Evolution of driving X chromosomes and resistance factors in experimental populations of Drosophila simulans
4350Capillon, CA, A., Evolution, 53:506-517. 1999-01-08 00:00:00.
Sex-ratio drive is a particular case of meiotic drive, described in several Drosophila species, that causes males bearing driving X chromosome to produce a large excess of females in their progeny. In Drosophila simulans, driving X chromosomes and resistance factors located on the Y chromosome and on the autosomes have been previously reported. In this paper, we report the study of the dynamics of sex-ratio factors in experimental populations. We followed the evolution in frequency of driving X chromosomes in the absence of resistance factors and the evolution of resistance factors in the presence of driving X chromosomes. The driving X chromosome was lost, contrarily to theoretical expectations that predict its rapid invasion. Autosomal resistances increased in frequency, and resistant Y chromosomes invaded the population very quickly, as predicted by theoretical models. Fitness measurements showed that the loss of the driving X chromosome was due to a strong deleterious effect that was expressed only when distorting males were in competition with standard males. However, the spread of autosomal resistances reduced this deleterious effect. Implications for the maintenance of polymorphism in natural populations are discussed.
Male eye span in stalk-eyed flies indicates genetic quality by meiotic drive suppression
4379Wilkinson, GSP, D. C.; Crymes, L., Nature, 391:276-279. 1998-01-17 00:00:00.
In some species, females choose mates possessing ornaments that predict offspring survival(1-5). However, sexual selection by female preference for male genetic quality(6-8) remains controversial because conventional genetic mechanisms maintain insufficient variation in male quality to account for costly preference and ornament evolution(9,10). Here we show that females prefer ornaments that indicate genetic quality generated by transmission conflict between the sex chromosomes, By comparing sex-ratio distributions in stalk-eyed fly (Cyrtodiopsis) progeny we found that female-biased sex ratios occur in species exhibiting eye-stalk sexual dimorphism(11,12) and female preferences for long eye span(13,14). Female-biased sex ratios result from meiotic drive(15), the preferential transmission of a 'selfish' X-chromosome. Artificial selection for 22 generations on male eye-stalk length in sexually dimorphic C. dalmanni produced longer eye-stalks and male-biased progeny sex ratios in replicate lines. Because male-biased progeny sex ratios occur when a drive-resistant Y chromosome pairs with a driving X chromosome(15), long eye span is genetically linked to meiotic drive: suppression. Male eye span therefore signals genetic quality by influencing the reproductive value of offspring(16).
Male sterility and meiotic drive associated with sex chromosome rearrangements in Drosophila: Role of X-Y pairing
4375McKee, BDW, K.; Merrill, C.; Ren, X. J., Genetics, 149:143-155. 1998-01-13 00:00:00.
In Drosophila melanogaster, deletions of the pericentromeric X heterochromatin cause X-Y nondisjunction, reduced male fertility and distorted sperm recovery ratios (meiotic drive) in combination with a normal Y chromosome and interact with Y-autosome translocations (T(Y;A)) to cause complete male sterility. The pericentromeric heterochromatin has been shown to contain the male-specific X-Y meiotic pairing sites, which consist mostly of a 240-bp repeated sequence in the intergenic spacers (IGS) of the rDNA repeats. The experiments in this paper address the relationship between X-Y pairing failure and the meiotic drive and sterility effects of Xh deletions. X-linked insertions either of complete rDNA repeats or of rDNA fragments that contain the IGS were found to suppress X-Y nondisjunction and meiotic drive in Xh(-)/Y males, and to restore fertility to Xh(-)/T(Y;A) males for eight of nine tested Y-autosome translocations. rDNA fragments devoid of IGS repeats proved incapable of suppressing either meiotic drive or chromosomal sterility. These results indicate that the various spermatogenic disruptions associated with X heterochromatic deletions are all consequences of X-Y pairing failure. We interpret these findings in terms of a novel model in which misalignment of chromosomes triggers a checkpoint that acts by disabling the spermatids that derive from affected spermatocytes.
Malaria: existing methods of vector control and molecular entomology
4369Curtis, CFT, H., British Medical Bulletin, 54:311-325. 1998-01-07 00:00:00.
In general, the most effective means of malaria vector control is the killing of adult mosquitoes with a residual insecticide applied to bednets or sprayed on house walls and ceilings. Major reductions in all-cause child mortality have been achieved in Africa by these means. In some circumstances, personal protection and larval control may also make a contribution. We discuss the prospects of genetic control by release of sterile male mosquitoes or driving genes for refractoriness to malaria into wild populations. Many major malaria vectors belong to complexes of sibling species which differ in vectorial and biological characteristics. Distinguishing the species by cytogenetic or molecular methods is important for epidemiological studies and could improve the targeting of control.
Wolbachia as a possible means of driving genes into populations
4368Curtis, CFS, S. P., Parasitology, 116:S111-S115. 1998-01-06 00:00:00.
Cytoplasmic incompatibility consists of sterility in cross matings, the crossing type being maternally inherited. It can be explained by the action of Wolbachia symbionts which are transmitted through the egg cytoplasm and leave an imprint on the sperm which prevents it fertilizing unless it is 'rescued' by the action of the same type of Wolbachia in the egg. Thus matings between infected males and uninfected females are sterile, but the reciprocal matings are fertile. Hence uninfected females are at risk of failing to transmit their uninfected cytoplasm if they cross mate, but infected females are at no such risk. Therefore natural selection favours the infected state and in two wild insect populations the infection has been observed spreading. If a gene for inability to transmit malaria could be introduced into Wolbachia and if this could be introduced into Anopheles (where these symbionts appear not to occur naturally), release of a limited number of such insects should trigger a process of displacement of malaria vectors, by the non-vector type. A simple model is used to demonstrate the limitations to this process which would be introduced by immigration.
Polymorphism for Y-linked suppressors of sex-ratio in two natural populations of Drosophila mediopunctata
4383Carvalho, ABV, S. C.; Klaczko, L. B., Genetics, 146:891-902. 1997-01-21 00:00:00.
In several Drosophila species there is a trait known as ''sex-ratio'': males carrying certain X chromosomes (called ''SR'') produce female biased progenies due to X-Y meiotic drive. In Drosophila mediopunctata this trait has a variable expression due to Y-linked suppressors of sex-ratio expression, among other factors. There are two types of Y chromosomes (suppressor and nonsuppressor) and two types of SR chromosomes (suppressible and unsuppressible). Sex-ratio expression is suppressed in males with the SRsuppressible/Y-suppressor genotype, whereas the remaining three genotypes produce female biased progenies. Now we have found that similar to 10-20% of the Y chromosomes from two natural populations 1500 km apart are suppressors of sex-ratio expression. Preliminary estimates indicate that Y-suppressor has a meiotic drive advantage of 6% over Y-nonsuppressor. This Y polymorphism for a nonneutral trait is unexpected under current population genetics theory. We propose that this polymorphism is stabilized by an equilibrium between meiotic drive and natural selection, resulting from interactions in the population dynamics of X and Y alleles. Numerical simulations showed that this mechanism may stabilize nonneutral Y polymorphisms such as we have found in D. mediopunctata.
The sex-ratio trait in Drosophila simulans: Geographical distribution of distortion and resistance
4381Atlan, AM, H.; Landre, C.; Montchamp-Moreau, C., Evolution, 51:1886-1895. 1997-01-19 00:00:00.
The sex-ratio trait we describe here in Drosophila simulans results from X-linked meiotic drive. Males bearing a driving X chromosome can produce a large excess of females (about 90%) in their progeny. This is, however, rarely the case in the wild, where resistance factors, including autosomal suppressors and insensitive Y chromosomes, prevent the expression of the driver. In this study, we searched for drive and resistance factors in strains of Drosophila simulans collected all over the world. Driving X chromosomes were found in all populations whenever a good sample size was available. Their frequency may reach up to 60%. However, the presence of driving X chromosomes never results in an excess of females, due to the systematic co-occurrence of resistance factors. The highest frequencies of driving X chromosomes were observed in islands, while populations from East and Central Africa (the supposed center of origin of the species) showed the highest level of resistance. The geographical pattern of drive and resistance factors, as well as the results of crosses between strains from different geographical areas, suggest that the sex-ratio system described here has a unique and ancient origin in the species.
Sex chromosome meiotic drive in stalk-eyed flies
4388Presgraves, DCS, E.; Wilkinson, G. S., Genetics, 147:1169-1180. 1997-01-06 00:00:00.
Meiotically driven sex chromosomes can quickly spread to fixation and cause population extinction unless balanced by selection or suppressed by genetic modifiers. We report results of genetic analyses that demonstrate that extreme female-biased sex ratios in two sister species of stalk-eyed flies, Cyrtodiopsis dalmanni and C. whitei, are due to a meiotic drive element on the X chromosome (X-d). Relatively high frequencies of X-d in C. dalmanni and C. whitei (13-17% and 29%, respectively) cause female-biased sex ratios in natural populations of both species. Sex ratio distortion is associated with spermatid degeneration in male carriers of X-d. Variation in sex ratios is caused by Y-linked and autosomal factors that decrease the intensity of meiotic drive. Y-linked polymorphism for resistance to drive exists in C. dalmanni in which a resistant Y chromosome reduces the intensity and reverses the direction of meiotic drive. When paired with X-d, modifying Y chromosomes (Y-m) cause the transmission of predominantly Y-bearing sperm, and on average, production of 63% male progeny. The absence of sex ratio distortion in closely related monomorphic outgroup species suggests that this meiotic drive system may predate the origin of C. whitei and C. dalmanni. We discuss factors likely to be involved in the persistence of these sex linked polymorphisms and consider the impact of X-d on the operational sex ratio and the intensity of sexual selection in these extremely sexually dimorphic flies.
Abnormal spermiogenesis is associated with the X-linked sex-ratio trait in Drosophila simulans
4385MontchampMoreau, CJ, D., Heredity, 79:24-30. 1997-01-03 00:00:00.
The sex-ratio trait, known in several Drosophila species, results from X-linked meiotic drive that affects Y-bearing sperm and causes males to produce female-biased progeny. We describe spermiogenesis in three types of D, simulans males: wild-type, sex-ratio, and males that bear driver X chromosomes but do not express the sex-ratio trait because of autosomal and Y-linked suppression, Sex-ratio males show numerous spermatid nuclei in abnormal positions throughout their cysts, which occurs rarely, if ever, in the two other types, The degree of the spermiogenic failure in sex-ratio males is correlated with the bias towards females in their progeny. This proves that: the trait is a case of meiotic drive and strongly suggests that the abnormal spermatids are Y-bearing ones, The number of cysts per testis, hence the production of X-bearing sperm. is not increased in sex-ratio males. Implications for the spread of the sex-ratio trait in natural populations of D. simulans are discussed.
The effect of B chromosomes on mating success of the grasshopper Eyprepocnemis plorans
4397Martin, SA, P.; HenriquesGil, N., Genetica, 97:197-203. 1996-01-15 00:00:00.
The mating ability of E. plorans was tested in laboratory conditions in six experimental units composed of ten males and fifteen females during 31 days. When significant differences were found (three from the six cages, and in totals) they involved a decrease of matings involving males with B chromosomes. The same tendency seems to exist in females, but to a lesser extent, so that a significant effect is only detected when the totals are considered. Accessory chromosomes also delay, in both sexes, the occurrence of the first mating. No mating preferences depending on the number of Bs were detected.
Further evidence consistent with Stellate’s involvement in meiotic drive
4394Hurst, LD, Genetics, 142:641-643. 1996-01-12 00:00:00.
STELLATE is an X-linked multicopy gene found in Drosophila melanogaster and is one of the most bizarre gene arrays yet described (for details see HARDY et al. 1984; LIVAK 1984, 1990; DANILEVSKAYA et al. 1991; BAW~REVA et al. 1992; SHEVELYOV 1992; PALUMBO et al. 1994). The activity of Stellate is restricted to spermatogenesis. However, the transcription and translation of Stellate is inhibited in most males by a Y-linked multicopy gene, Suppressor of Stellate (Su(Ste)) alias crystal (q) . If Stellate is not suppressed, then the protein product (homologous to the beta subunit of casein kinase 11) is produced at levels dependent upon the copy number of Stellate. If Stellate copy number is relatively low, then linear crystals form and the males are of reduced, but nonzero, fertility. In high copy number (up to 200), however, the protein forms a star-shaped crystal in sperm, and the males are typically sterile. An understanding of this system is hence potentially of importance for the study of both intra- and inter-specific sterility and hence of HALDANE’S Rule
Evidence for B chromosome drive suppression in the grasshopper Eyprepocnemis plorans
4393Herrera, JAL, M. D.; Cabrero, J.; Shaw, M. W.; Camacho, J. P. M., Heredity, 76:633-639. 1996-01-11 00:00:00.
The grasshopper Eyprepocnemis plorans is polymorphic for both a B chromosome and a heterochromatic segment of chromatin on the smallest autosome. Females transmit these to their offspring more frequently after copulating with a male from a population without Bs than after copulating with a male from their own population. Paternity analyses using the heterochromatic segment as a marker showed that the effect of male on female transmission does not depend on fertilization because it occurs even when all the eggs are fertilized by sperm from another mating. The possible mechanisms include behavioural differences in mating and transfer of substances affecting female meiosis in male ejaculate. The data support the idea that the B chromosome is initially subject to meiotic drive in populations in which it has not previously existed, and that genes which suppress this drive are then selected.
Functional identification of the Segregation Distorter locus of Drosophila melanogaster by germline transformation
4415McLean, JRM, C. J.; Powers, P. A.; Ganetzky, B., Genetics, 137:201-209. 1994-01-13 00:00:00.
Segregation Distorter (SD) is a meiotic drive system in D. melanogaster that results in the failure of SD/SD+ males to transmit SD+ homologs owing to the induced dysfunction of spermatids carrying the normal chromosome. Segregation distorter (Sd), the gene primarily responsible for this distorted transmission, is associated with a novel 12-kb restriction fragment containing a tandem duplication of a 5-kb wild-type segment of genomic DNA. When introduced into appropriate genetic backgrounds by germline transformation, this 12-kb fragment causes full levels of distortion and directs the expression of an Sd-specific 4-kb transcript. Transformants that have lost part of this segment are unable to cause distortion and do not express the 4-kb transcript. These results identify the tandem duplication as Sd.
Y-linked suppressors of the sex-ratio trait in Drosophila mediopunctata
4412Decarvalho, ABK, L. B., Heredity, 73:573-579. 1994-01-10 00:00:00.
X-linked meiotic drive causing female-biased progenies is known to occur in nine Drosophila species and is called 'sex-ratio'. In D. mediopunctata this trait is associated with the X:21 chromosome inversion and has variable expression. We describe here a powerful Y-linked suppressor system of sex-ratio expression in this species. There are two types of Y chromosomes (suppressor and nonsuppressor) and two types of X:21 chromosomes (suppressible and unsuppressible). Sex-ratio expression is suppressed in males with the 21 (suppressible)/Y-suppressor genotype, whereas the remaining three genotypes produce female-biased progenies.
Bewildering Bs – An impression of the 1st B-chromosome conference
4408Beukeboom, LW, Heredity, 73:328-336. 1994-01-06 00:00:00.
Ever since their first discovery B chromosomes have attracted attention. Why are they so appealing? The standard chromosomes of an organism are A chromosomes; B chromosomes are extra to this normal complement. In the B chromosome 'bible' (Jones & Rees, 1982) Bs are defined as dispensable supernumerary chromosomes that are not homologous and do not pair with A chromosomes. They have been further characterized as (1) morphologically different from As (usually smaller), (2) being inherited in a nonMendelian fashion, (3) not (or only rarely) having nucleolus organisers, (4) often displaying nondisjunction at anaphase of mitosis resulting in frequencies varying between organs in the same individual, (5) reducing fertility and growth when present in high numbers, and (6) carrying no genes with major effects. These features of Bs were recently discussed at an international conference and the main ideas presented by the participants are reported here. From 21 to 25 September 19
The Segregation Distorter (SD) complex and the accumulation of deleterious genes in laboratory strains of Drosophila melanogaster
4423Dominguez, AS, E.; Albornoz, J.; Gutierrez, A., Theoretical and Applied Genetics, 87:479-486. 1993-01-21 00:00:00.
Segregation Distorter (SD) associated with the second chromosome of D. melanogaster is found in nature at equilibrium frequencies lower than 5%. We report extremely high frequencies of SD (30-50%) in two selected strains, established in 1976, and show it to be responsible for the accumulation of deleterious genes in chromosome II. Samples of chromosomes extracted over a 4-year period were characterized with respect to distortion, sensitivity, lethality, sterility, and inversions. SD chromosomes were inversion-free as they have been shown to be in the Mediterranean area. The cosmopolitan inversion In(2L)t was found associated with SD+ chromosomes. Lines polymorphic for SD have accumulated linked lethal and female-sterile genes approaching a near balanced system. It is proposed that deleterious genes linked in coupling to SD were accumulated by the balancing effect of distortion, while drift and restricted recombination account for the accumulation of deleterious genes linked in repulsion by a mechanism similar to Muller's ratchet. Our results should not be viewed as a particular case as SD chromosomes associated with detrimental genes and inversions are present in almost all populations around the world. The system could evolve in the way we describe whenever equilibrium conditions are broken down in small populations and lead to an increase in SD frequency.
Autosomal suppressors of sex-ratio in Drosophila mediopunctata
4422Decarvalho, ABK, L. B., Heredity, 71:546-551. 1993-01-20 00:00:00.
The sex-ratio trait has been described as the production of progenies with excess of females due to X-linked meiotic drive in the parental males. This trait has a variable expression in Drosophila mediopunctata. We describe here the existence and chromosomal localization of autosomal suppressors of sex-ratio in this species. There are at least four such genes (one on each major autosome) and the strongest effect.is localized on chromosome IV. These genes possibly result from the operation of 'Fisher's Principle'; a mechanism of Natural Selection leading to a 1:1 sex ratio.
Deletion analysis of the selfish B-chromosome, Paternal Sex-Ratio (PSR), in the parasitic wasp Nasonia vitripennis
4420Beukeboom, LWW, J. H., Genetics, 133:637-648. 1993-01-18 00:00:00.
Paternal Sex Ratio (PSR) is a ''selfish'' B chromosome in the parasitoid wasp Nasonia vitripennis. It is transmitted via sperm, but causes supercondensation and destruction of the paternal chromosomes in early fertilized eggs. Because this wasp has haplodiploid sex determination, the effect of PSR is to convert diploid (female) eggs into haploid (male) eggs that carry PSR. Characterizing its genetic structure is a first step toward understanding mechanisms of PSR action. The chromosome is largely heterochromatic and contains several tandemly repeated DNA sequences that are not present on the autosomes. A deletion analysis of PSR was performed to investigate organization of repeats and location of functional domains causing paternal chromosome destruction. Deletion profiles using probes to PSR-specific repetitive DNA indicate that most repeats are organized in blocks on the chromosome. This study shows that the functional domains of PSR can be deleted, resulting in nonfunctional PSR chromosomes that are transmitted to daughters. A functional domain may be linked with the psr22 repeat, but function may also depend on abundance of PSR-specific repeats on the chromosome. It is hypothesized that the repeats act as a ''sink'' for a product required for proper paternal chromosome processing. Almost all deletion chromosomes remained either functional of nonfunctional in subsequent generations following their creation. One chromosome was exceptional in that it reverted from nonfunctionality to functionality in one lineage. Transmission rates of nonfunctional deletion chromosomes were high through haploid males, but low through diploid females.
Transmission and expression of the parasitic Paternal Sex-Ratio (PSR) chromosome
4419Beukeboom, LWW, J. H., Heredity, 70:437-443. 1993-01-17 00:00:00.
B-chromosomes are often considered genomic parasites. They are extra to the normal chromosomal complement, are unnecessary for survival of an individual, and are often inherited at higher than Mendelian rates. Paternal Sex Ratio (PSR) is an extreme example of a parasitic B-chromosome in the wasp Nasonia vitripennis. It is transmitted via sperm but then destroys the other paternal chromosomes in the early fertilized egg. PSR disrupts the normal haplodiploid sex determination system of this wasp by converting diploid (female) eggs into haploid eggs that develop into PSR-bearing males. Transmission and expression of PSR was measured in single pair crosses between carrier males and standard females. Presence of the chromosome was detected by probing offspring with PSR-specific repetitive DNA. Most (equal to or more than 90 per cent) PSR males produced all-male offspring. Overall transmission rates of PSR to fertilized eggs varied beween 0.94 and 1.0. Some males (up to 10 per cent) produced daughters at varying frequencies. Of 226 daughters tested, only one carried PSR (and this may have been a laboratory error) indicating that daughters result from failure of transmission rather than loss of expression. Transmission of PSR to males in families that included female offspring varied from 0 to 94 per cent. Incomplete transmission is most likely the result of loss of PSR in some spermatogonial cell lineages and indicates some mitotic instability. Implications of the results to the aetiology and population genetics of PSR are discussed.
The evolution of unusual chromosomal systems in coccoids: Extraordinary sex-ratios revisited
4424Haig, D, Journal of Evolutionary Biology, 6:69-77. 1993-01-02 00:00:00.
Coccoids (scale insects) exhibit a wide variety of chromosomal systems. In many species, paternal chromosomes are eliminated from the male germline such that all of a male's sperm transmit an identical set of maternal chromosomes. In such species, an offspring's sex is determined by whether or not paternal chromosomes are inactivated in the egg's cytoplasm after fertilization. This paper presents a model of the evolution of paternal genome loss in coccoids from an ancestral system of XX-XO sex determination. The model is based on Hamilton's (1967) theory that different genetic elements within the genome have different unbeatable sex ratios. In this model (1) meiotic drive by the X chromosome in XO males causes female-biased sex ratios; (2) the maternal set of autosomes in males evolves effective sex linkage to exploit X-drive; and (3) genes expressed in mothers are selected to convert some of their XX daughters into sons. A similar model may explain the evolution of haplodiploidy.
Male and female segregation distortion for heterochromatic supernumerary segments on the s(8) chromosome of the grasshopper Chorthippus jacobsi
4432Lopezleon, MDC, J.; Camacho, J. P. M., Chromosoma, 101:511-516. 1992-01-10 00:00:00.
The mode of inheritance of supernumerary segments located on three different chromosome pairs was investigated in controlled crosses with specimens of the grasshopper Chorthippus jacobsi. While extra segments located on chromosomes M5 and M6 showed Mendelian inheritance, that on S8 did not. Thus, the two supernumerary heterochromatic chromosome segments located distally on the S8 chromosome accumulated through non-Mendelian transmission through both sexes. The observed transmission patterns may be explained by gametic selection for spermatozoa carrying segmented S8 chromosomes, in addition to meiotic drive for segmented S8 chromosomes in heterozygous females. The significance of these findings for the maintenance of these polymorphisms in natural populations is discussed.
Population genetics of a parasitic chromosome – Experimental analysis of PSR in subdivided populaltions
4431Beukeboom, LWW, J. H., Evolution, 46:1257-1268. 1992-01-09 00:00:00.
Nasonia vitripennis is a parasitoid wasp that harbors several non-Mendelian sex-ratio distorters. These include MSR (Maternal Sex Ratio), a cytoplasmic element that causes nearly all-female families, and PSR (Paternal Sex Ratio), a supernumerary chromosome that causes all-male families. As in other hymenoptera, N. vitripennis has haplodiploid sex determination. Normally, unfertilized (haploid) eggs develop into males and fertilized (diploid) eggs develop into females. The PSR chromosome violates this normal pattern; it is inherited through sperm, but then causes destruction of the paternal chromosomes (except itself, thus converting diploid fertilized eggs (normally females) into haploid eggs that develop into PSR-bearing males. PSR is an extreme example of "parasitic" or "selfish" DNA. Because N. vitripennis has a highly subdivided population structure in nature, population-level selection may be important in determining the dynamics of PSR in natural populations. A theoretical analysis shows that subdivided population structure reduces PSR frequency, whereas high fertilization proportion (such as produced by the MSR element) increases PSR frequency. Population experiments using two deme sizes (3- and 12-foundress groups) and strains producing two fertilization proportions [wild-type (LabII)-57-67% female, and MSR (MI)-90-93% female] confirm these predictions. PSR achieved frequencies over 0.90 in 12-foundress group MSR populations in contrast to 0.20-0.40 in wild-type 12-foundress populations. PSR was selected against in wild-type populations composed of three-foundress groups. In MSR populations with three-foundress groups, presence of PSR selected against the MSR cytoplasmic element, eventually leading to low frequencies of both PSR and MSR. Complicated dynamics may occur when these two sex-ratio distorters are both present in highly subdivided populations. The existence of PSR in natural populations may depend on the presence of MSR. Results indicate that population subdivision could be important in determining the frequency of sex ratio distorters in N. vitripennis.
Effects of deletions on mitotic stability of the Paternal Sex-Ratio (PSR) chromosome from Nasonia
4430Beukeboom, LWR, K. M.; Werren, J. H., Chromosoma, 102:20-26. 1992-01-08 00:00:00.
Paternal-Sex-Ratio (PSR) is a B chromosome that causes all-male offspring in the parasitoid wasp Nasonia vitripennis. It is only transmitted via sperm of carrier males and destroys the other paternal chromosomes during the first mitotic division of the fertilized egg. Because of haplodiploidy, the effect of PSR is to convert diploid (female) eggs into haploid eggs that develop into PSR-bearing males. The PSR chromosome was previously found to contain several families of repetitive DNA, which appear to be present in local blocks. PSR chromosomes with irradiation-induced deletions have decreased rates of transmission and increased variation in transmission. This study investigates whether these differences in transmission of deletion chromosomes are due to mitotic instability. Two deletion chromosomes (E306 and F316) and the wild-type PSR chromosome were examined. A cytogenetic assay of testes revealed that wild-type PSR males contained the chromosome in 98%-100% of their spermatocytes. Similar counts from carriers of two deletion chromosomes were lower and varied between individuals from 50%-100%. One F316 male did not contain the chromosome in any of its spermatocytes although the chromosome was present in somatic tissues based on hybridization to PSR-specific repetitive DNA. A molecular analysis of males found the wild-type PSR chromosome to be present in all somatic tissues. Tissue specific differences in the presence or PSR were found in several males from the two deletion lines. The results show that deletions can result in mosaicism due to increased mitotic instability of PSR. Such individuals sometimes partially or completely fail to transmit the chromosome. Patterns of mosaicism of 13 chromosomes in other organisms are discussed.
Meiotic drive in Lucilia cuprina and chromosomal evolution
4441Foster, GGW, M. J., American Naturalist, 137:403-415. 1991-01-19 00:00:00.
In females heterozygous for pericentric inversions that alter the relative lengths of the long and short arms of a chromosome, crossing-over within the inversion can lead to unequal segregation at anaphase II, favoring the homologue with the more centrally located centromere. It is suggested that this phenomenon may have played a role in the evolution of centromere position in certain species groups.
X-chromosome segregation distortion in Drosophila
4439Curtsinger, JW, American Naturalist, 137:344-348. 1991-01-17 00:00:00.
The sex-ratio trait exhibits both discrete and continuous variation in Drosophila pseudoobscura. The discrete variation is caused by X-chromosome meiotic drive. The evolutionary forces maintaining the meiotic-drive polymorphism include strong viability selection against homozygous females and virility selection in males. The relative importance of the two factors is unresolved. The evidence for a genetic component in the continuous sex-ratio variation comes from artificial-selection experiments, large-scale estimation of segregation ratios corrected for viability effects, and an examination of the rates of spermatid loss. Segregation ratio can be treated as a typical quantitative character subject to major and minor genetic modifiers.
Sex-ratio distortion caused by meiotic drive in mosquitos
4458Wood, RJN, M. E., American Naturalist, 137:379-391. 1991-01-16 00:00:00.
Meiotic-drive genes have been described in two species of mosquito, Aedes aegypti and Culex quinquefasciatus. In both species, a Y (M)-linked gene causes a change in sex ratio in favor of males. More is known about the Distorter gene (D) in A. aegypti, but the gene in C. quinquefasciatus appears to be similar. D is located on the right arm of the sex chromosome, is marked with the intercalary Giemsa C-band when present, and is linked closely to the sex locus or region. D undergoes meiotic drive only when in coupling with M, the male-determining gene, which does not recombine with the centromere. Sensitivity to the MD haplotype is controlled at m, the female-determining gene. Therefore, m is considered to be the responder. The m haplotype is polymorphic for sensitivity to MD (m(r1), m(r2), m(s1)-m(s6)). Sensitivity is influenced, in some strains, by a second sex-linked gene t (tolerance to Distorter). Another sex-linked gene, A, enhances the effect of D. Meiotic drive is associated with breaks on the sex chromosomes. First seen at diplotene, mainly at four discrete positions, 90% of these breaks occur on the X (m) chromosome. They usually appear on a chiasmic arm of the bivalent, with the result that most acentric fragments remain attached to the unbroken homologue by a chiasma. Examination of developing spermatozoa in Distorter males reveals extreme sperm depletion, a high degree of abnormality (e.g., multiple axonemes), and an increased DNA content up to the 4C level. Surprisingly, however, the effective fertility of these males is hardly reduced. Evidently, spermatozoa are produced in nondistorter males in vast excess. The Distorter gene has been found in populations from Africa, America, Australia, and Sri Lanka. Resistance to it is much more widespread. The presence of natural resistance argues against the use of D for population control, but its effect has been shown to be enhanced in the presence of certain translocations and the A gene, causing it to become effective in field cage trials, even in the presence of some resistance. There is also experimental support for using D to bring about changes in populations ("population replacement").
Why is Mendelian segregation so exact
4438Crow, JF, Bioessays, 13:305-312. 1991-01-16 00:00:00.
The precise 1:1 segregation of Mendelian heredity is ordinarily taken for granted, yet there are numerous examples of 'cheating' genes that perpetuate themselves in the population by biasing the Mendelian process in their favor. One example is the Segregation Distortion system of Drosophila melanogaster, in which the distorting gene causes its homologous chromosome to produce a nonfunctional sperm. This system depends on three closely linked components, whose molecular basis is beginning to be understood. The system is characterized by numerous modifiers changing the degree of distortion. Mathematical theory shows that unlinked modifiers that change the degree of distortion in the direction of Mendelism always increase in the population. This provides a mechanism for removing cheaters and preserving the honesty of the Mendelian gene-shuffle.
Male sex-ratio trait in Drosophila pseudoobscura: Frequency of autosomal aneuploid sperm
4437Cobbs, GJ, L.; Gordon, L., Genetics, 127:381-390. 1991-01-15 00:00:00.
Males with the SR X chromosome show the "sex-ratio" (sr) phenotype in which they produce almost entirely daughters. The few sons (about 1%) are invariably sterile X/O males and result entirely from nullo-XY sperm. The "male-sex-ratio" (msr) phenotype is a modified form of sr in which SR/Y males produce a higher frequency of sterile X/O sons. The msr trait is due to the presence of the SR X-chromosome in males which are also homozygous for one or more autosomes from the L116 strain. Here the frequency of nullo-3 and diplo-3 sperm from msr males was measured by crossing to a compound-3 strain and found to be 13.8% and 3.2%, respectively, of the total viable sperm. The sr males produced very low levels of nullo-3 sperm at a frequency not different from control X/Y males and a slightly elevated frequency of diplo-3 sperm over X/Y males. The msr males were found to have only 12% the fecundity of sr males and in matings to cause a high frequency of brown inviable eggs. These results indicate that high rates of autosomal aneuploidy are not restricted to chromosome 3 but also occur for chromosomes 2, 4 and 5. The overall frequency of autosomal aneuploid sperm is estimated to be approximately 50%. Microscopic studies of meiosis in testes from msr males indicates meiotic nondisjunction and meiotic chromosome loss are responsible for the msr phenotype. Last, microscopic studies of sperm cysts from msr males reveal high levels of spermiogenic failure.
The paternal-sex-ratio chromosome of Nasonia
4457Werren, JH, American Naturalist, 137:392-402. 1991-01-15 00:00:00.
Paternal sex ratio (PSR) is a supernumerary chromosome that is transmitted through sperm to fertilized eggs and then gains a transmission advantage by causing supercondensation of the paternal chromosomes (except itself). Because of haplodiploidy, this converts diploid females into haploid (PSR) males. PSR gains a transmission advantage because the unpaired chromosome has a higher frequency of transmission through male (mitotic) gametngenesis than through female (meiotic) gametogenesis. PSR increases in panmictic populations that produce more than 50% fertilized eggs. PSR frequency is typically reduced by population subdivision because of increased local competition among PSR males and reduced availability of females resulting from PSR action. Genetic and molecular studies of PSR have recently begun. PSR is highly heterochromatic and contains large tandem arrays of repetitive DNA unique to it. PSR apparently acts by "imprinting" the set of paternal chromosomes, resulting in their supercondensation during mitosis. Deletion studies are under way to characterize the genetic basis of PSR action and "protection" from its own action.
Sex ratio polymorphism in Drosophila pseudoobscura
4436Beckenbach, AT, American Naturalist, 137:340-343. 1991-01-14 00:00:00.
I studied "sex-ratio" (SR) genotype frequencies in two populations of Drosophila pseudoobscura from southeastern Arizona: Bear Creek Canyon and Tucson. Wild-inseminated females were collected, their fecundities measured in the laboratory, and their SR genotypes inferred by cytological analysis of their progenies. A statistically significant fecundity deficiency was observed among SR/SR females from Bear Creek Canyon. The SR frequency in the Tucson population increased at a rate consistent with the operation of meiotic drive unopposed by selection.
Segregation distortion in Drosophila melanogaster: Genetic and molecular analysis
4455Temin, RGG, B.; Powers, P. A.; Lyttle, T. W.; Pimpinelli, S.; Dimitri, P.; Wu, C. I.; Hiraizumi, Y., American Naturalist, 137:287-331. 1991-01-13 00:00:00.
The Segregation Distorter (SD) complex in the centromeric region of chromosome 2 in Drosophila melanogaster is responsible for a naturally occurring and strong system of male meiotic drive. Earlier recombinational dissection and deletional analysis showed that the SD complex resolves into three major loci: the euchromatic Sd, or Segregation distorter gene at the base of the left arm of the chromosome (2L), and two heterochromatic genes: E(SD), the Enhancer of SD, and Rsp, the Responder, in the center of the left arm and the right arm (2R), respectively. Rsp exists in the major allelic forms, Rsp(s), for sensitive, and Rsp(i), for insensitive. Males that are heterozygous for an SD chromosome (SdE(SD)Rsp(i)) and a sensitive SD+ homologue (Sd+ E(SD)+ Rsp(s)) transmit predominantly or even exclusively the SD-bearing chromosome to the progeny. The distortion of the segregation ratio is traceable to failure in chromatin condensation and maturation of those spermatids that receive the Rsp(s) homologue during meiosis. Characterization of the properties of null alleles of Sd, E(SD), and Rsp that were generated by delection determined the precise cytological locations of the components and established the functional relationship of each to its wild-type counterpart, suggesting a model whereby a deleterious action of Sd, along with E(SD), on the Rsp(s) target sets in motion the events culminating in sperm dysfunction. Further genetic analysis of E(SD), a gene required for full expression of drive, showed that E(SD) in two doses can cause significant distortion even in the absence of Sd. This distortion is suppressible by a suppressor of SD action. Thus, E(SD) is more than a simple modifier of Sd; rather, it is an effector locus that, like Sd, can act at the Rsp(s) target. Cloning and molecular analysis of the Sd locus reveal that the alteration uniquely associated with Sd is a 5-kb tandem duplication within the polytene band 37D5, which is where Sd is known to map. The Sd-associated duplication appears to be part of a large gene about 100 kb in size. A 4.2-kb SD-specific transcript has been identified, and analyses of the cDNAs indicate a complex transcription pattern. Since Responder plays such a key role in segregation distortion, recent progress in analyzing this locus has been exciting. Studies of Rsp at the genetic, cytogenetic, and molecular levels have been mutually reinforcing and consistent in demonstrating that Rsp is an extended locus that is (1) subdivisible and (2) associated with a 120-bp repeated sequence of DNA that is rich in adenine-thymine pairs and whose copy number is correlated with the degree of sensitivity. In an exceptional situation, there are certain Sd Rsp(i)/Sd+ Rsp(s) males carrying particular modifiers in which the Rsp(i) chromosome can be transmitted at frequencies of less than 0.50 relative to the Rsp(s) chromosome, suggesting that the genetics of segregation ratios may involve even further complexities, which need to be unraveled.
On the components of Segregation Distortion in Drosophila melanogaster 5: Molecular analysis of the SD locus
4453Powers, PAG, B., Genetics, 129:133-144. 1991-01-11 00:00:00.
Segregation Distorter (SD) is a naturally occurring meiotic drive system comprising at least three distinct loci: Sd, Rsp and E(SD). Heterozygous SD/SD+ males transmit the SD chromosome in vast excess over the normal homolog. The distorted transmission involves the induced dysfunction of the spermatids that receive the SD+ chromosome. In the 220-kb region of DNA that contains the Sd gene, we identified a 5-kb tandem duplication that is uniquely associated with all SD chromosomes, absent in SD+ chromosomes, and detectably altered in Sd revertants. On northern blots, genomic probes from the tandem duplication detect an SD-specific 4-kb transcript in addition to several smaller transcripts present in both SD and SD+. Seven classes of cDNAs derived from these transcripts have been isolated. All of these cDNAs share extensive sequence identity at their 3' ends but differ at their 5' ends. Sequence analysis indicates that these cDNAs potentially encode four distinct, but related, polypeptides. Introduction of the tandem duplication into SD+ flies by germline transformation did not confer the dominant gain-of-function Sd phenotype. This result, taken together with our analysis of the Sd cDNAs, suggests that the duplication is part of a much larger gene that encodes several different polypeptides.
X-Y pairing, meiotic drive and ribosomal DNA in Drosophila melanogaster males
4452McKee, BD, American Naturalist, 137:332-339. 1991-01-10 00:00:00.
One of the genotypic features responsible for sex-chromosome meiotic drive and sterility in Drosophila melanogaster males has now been defined clearly. Separation of a significant fraction of X euchromatin from the X pairing site causes either meiotic drive or sterility, depending on whether the separation occurs alone or in combination with rearrangements involving the Y chromosome. The relationship between X-chromosome integrity and the late-spermatid developmental breakdowns responsible for meiotic drive and sterility is still not understood. X-Y pairing is important for some aspect of spermatogenesis in addition to its role in X-Y disjunction. Transcriptional inactivation and meiotic timing are two possibilities that are worth exploring, and there are likely to be others. With molecular probes for genes active in spermatogenesis becoming available, ideas such as the pairing dependence of transcriptional inactivation should become amenable to direct tests. It is hoped that an increased use of molecular methods will shed new light on this fascinating genetic problem.
Meiotic drive against an autosomal supernumerary segment promoted by the presence of a B-chromosome in females of the grasshopper Eyprepocnemis plorans
4448Lopezleon, MDC, J.; Camacho, J. P. M., Chromosoma, 100:282-287. 1991-01-06 00:00:00.
Twenty-seven out of 50 progeny analyses performed with specimens of the grasshopper Eyprepocnemis plorans were informative about the transmission of a supernumerary heterochromatic chromosome segment. The simultaneous presence of a B chromosome in some of the parents involved in the crosses permitted us to test the relationship between both types of supernumerary heterochromatin with respect to their transmission. The results demonstrated that the supernumerary segment is partly eliminated through females possessing B chromosomes. The implications of this in relation to the occurrence of the extra segment in natural populations are discussed.
Sander,Larry – The father of meiotic drive
4447Lindsley, DL, American Naturalist, 137:283-286. 1991-01-05 00:00:00.
The symposium at which the following papers were presented was deprived of what surely would have been a major intellectual contribution by the sudden death of its co-organizer, Larry Sandler, in February 1987. Larry was a leading contributor to the study of segregation distortion and meiotic drive, beginning with his seminal research as a graduate student with Ed Novitski at the University of Missouri and continuing, in collaboration with Yuichiro Hiraizumi, as a post- doctoral fellow with Jim Crow and as a fledgling faculty member at the University of Wisconsin. Many of us at the conference worked with him personally and benefited from his insights and his enthusiasm for genetic analysis of meiotic problems. We all felt a great sense of loss and missed his lively contributions at the symposium.
Tsetse fly eradication in Burkina Faso and evaluation of traps and targets
26174M. Clair, D. Cuisance, H. Politzar, P. Merot and B. Bauer, STERILE INSECT TECHNIQUE FOR TSETSE CONTROL AND ERADICATION, 1990-05-01 14:50:02.
Control operations against tsetse flies with the sterile insect technique (SIT) were conducted by the Centre de recherches sur les trypanosomoses animales (CRTA) (Institut d’élevage et de médecine vétérinaire des pays tropicaux/Gesellschaft fur Technische Zusammenarbeit (IEMVT/GTZ) Project), Bobo-Dioulasso (Burkina Faso). The project ended in 1984 with the eradication in the Sideradougou pastoral zone ofthe three tsetse species present there (Glossina palpalis gambiensis, G. tachinoides and G. morsitans submorsitans). Since 1985, besides monitoring of this area, the CRTA oriented its activities towards improving trapping by carrying out research on the form and colour of targets as well as the use of olfactory attractants.
Sex-ratio meiotic drive in Drosophila testacea
4462James, ACJ, J., Genetics, 126:651-656. 1990-01-20 00:00:00.
We document the occurrence of "sex ratio" meiotic drive in natural populations of Drosophila testacea. "Sex ratio" males sire greater than 95% female offspring. Genetic analysis reveals that this effect is due to a meiotically driven X chromosome, as in other species of Drosophila in which "sex ratio" has been found. In contrast to other drosophilids, the "sex ratio" and standard chromosomes of D. testacea do not differ in gene arrangement, implying that the effect may be due to a single genetic factor in this species. In all likelihood, the "sex ratio" condition has evolved independently in D. testacea and in the Drosophila obscura species group, as the loci responsible for the effect occur on different chromosomal elements. An important ecological consequence of "sex ratio" is that natural populations of D. testacea exhibit a strong female bias. Because D. testacea mates, oviposits, and feeds as adults and larvae on mushrooms, this species provides an excellent opportunity to study the selective factors in nature that prevent "sex ratio" chromosomes from increasing to fixation and causing the extinction of the species.
Thte genetic basis of resistance and sensitivity to the meiotic drive gene D in the mosquito Aedes aegypti L.
4469Wood, RJO, N. A., Genetica, 72:69-79. 1987-01-07 00:00:00.
A study has been made on the genetic basis of meiotic drive at the Distorter (D) locus which, in coupling with the male-determining gene (or region) M on the Y chromosome, causes production of excess male progeny. Its effect is regulated by the sensitivity/resistance of the X chromosome. This study demonstrates that there are two major loci controlling resistance/sensitivity to MD: (1) the m gene (or region) on the X chromosome (allelic with M) which may be either m R or m S (resistant or sensitive), (2) the t (tolerance) gene (or genes) which recombines with m and, if present, largely counteracts the effect of m S . There is also evidence that MD itself is capable of limited adaptation.; ; The conclusions were derived from using MD males of the T30 or ACCRA strains (from Trinidad and Ghana respectively). The work involved the use of the CHIPEI and RED strains with sensitive X chromosomes, the latter also carrying the t (tolerance) gene which is linked to re (red eye) and m (the sex-determining locus or region) but recombines with both. The implications of these findings for using MD as a method of population control are discussed.
Abnormal salivary gland puff associated with meiotic drive in mosquitos (Diptera, Culicidae)
4468Sweeny, TLG, P.; Barr, A. R., Journal of Medical Entomology, 24:623-627. 1987-01-06 00:00:00.
A meiotic drive factor, distorter (d), has been described previously for Culex pipiens L. mosquitoes. Males homozygous for the gene (Md/md) produce few female offspring owing to breakage of the female-determining dyad of chromosome 1 (the sex chromosome) during the first meiotic division of spermatogenesis. Orcein squash preparations of polytene salivary gland chromosomes of the distorter strain revealed a chromosome break and other abnormalities at zone 10C3, the location of a large puff that has been reported to be associated with sex determination in C. pipiens. In the polytene chromosomes, d apparently disrupts normal expansion and contraction of the puff. Zone 10C3 probably is also the breakpoint of the female-determining dyad. Zone 10C3 on the male-determining dyad seems to be resistant to the action of d, whereas zone 10C3 on the female-determining dyad is vulnerable to the destructive action of d. Possibly the break in the female-determining dyad occurs directly at m, the gene locus for "femaleness" in C. pipiens, in which case d may be a mutated form of m.
Control of meiotic drive of B-chromosomes in the mealybug, Pseudococcus affinis (obscurus)
4467Nur, UB, B. L. H., Genetics, 115:499-510. 1987-01-05 00:00:00.
Isofemale lines of Pseudococcus affznis (MASKELL) differ in their ability to maintain B chromosomes (Bs) due to the presence of genotypes that affect the rate of transmission (k) of the Bs. The nature of these genotypes was analyzed by comparing ks of males carrying the same B and the same paternal genome (which is heterochromatic), but differing in their maternal genome. In males from line L-60, which maintained the B at a frequency of over 4.0 Bs per individual, the mean k varied between 0.7 and 0.95 in different experiments. Over the same period, the mean k of males with a maternal genome from one of two lines in which the B was rapidly lost (L-1 19), increased from 0.5 to 0.9, and that of the other line (L-230) decreased gradually from 0.6 to less than 0.1. The ks appear not to be correlated with the geographical or parental origin of the B. The observed changes in k are attributed at least in part to changes in the frequency of genotypes (alleles) which can drastically reduce the transmission of the B and, when present in high frequency, can lead to its rapid loss. The frequency distribution of the ks of sons of F, females from the cross L-230 X L-60 suggests that the two lines differ at two unlinked loci with additive effects on k. The genome of L-119 also caused the B to undergo nondisjunction in about 10% of the primary spermatocytes. A comparison between the ks of the males tested and those of males from a natural population suggests that in that population the B is “parasitic” and that the frequency of transmission-reducing genotypes is low.
X-4 Translocation and meiotic drive in Drosophila melanogaster males: Role of sex chromosome pairing
4466McKee, B, Genetics, 116:409-413. 1987-01-04 00:00:00.
Males carrying certain X-4 translocations exhibit strongly skewed sperm recovery ratios. The Xp4D half of the translocation disjoins regularly from the Y chromosome and the 4‘XD half disjoins regularly from the normal 4. Yet the smaller member of each bivalent is recovered in excess of its pairing partner, apparently due to differential gametic lethality. Chromosome recovery probabilities are multiplicative; the viability of each genotype is the product of the recovery probability of its component chromosomes. Meiotic drive can also be caused by deficiency for X heterochromatin. In( I)scQLscBR males show the same size dependent chromosome recoveries and multiplicative recovery probabilities found in T(1;4)Bs males. Meiotic drive in Zn(I)scQLscBR males has been shown to be due to X-Y pairing failure. Although pairing is regular in the T(X;4) males, the striking phenotypic parallels suggest a common explanation. The experiments described below show that the two phenomena are, in fact, one and the same. X-4 translocations are shown to have the same effect on recovery of independently assorting chromosomes as does Zn(I)scqLscgR. Addition of pairing sites to the 4pXD half of the translocation eliminates drive. A common explanation-failure of the distal euchromatic portion of the X chromosome to participate in XY meiotic pairing-is suggested as the cause for drive. The effect of X chromosome breakpoint on X-4 translocation induced meiotic drive is investigated. It is found that translocations with breakpoints distal to 13C on the salivary map do not cause drive while translocations broken proximal to 13C cause drive. The level of drive is related to the position of the breakpoint-the more proximal the breakpoint the greater the drive.
The eradication of Glossina-palpalis-palpalis (Robineau-Desvoidy) (diptera, Glossinidae) using traps, insecticide-impregnated targets and the sterile insect technique in central Nigeria
26155W. Takken, M. A. Oladunmade, L. Dengwat, H. U. Feldmann, J. A. Onah, S. O. Tenabe and H. J. Hamann, Bulletin of Entomological Research, 76:275-286. 1986-06-01 13:33:24.
The integrated use of biconical traps, insecticide-impregnated targets and the sterile insect technique was developed for the eradication of Glossina palpalis palpalis (Robineau-Desvoidy) in a 1500-km2 area of central Nigeria. Six weeks or more of continuous removal trapping, using biconical traps, reduced the target tsetse population by more than 90% but failed to eradicate it. Males sterilized by irradiation from a ^Co source that were then released weekly induced significant sterility in target females and were successful in helping to eradicate the target population. A minimum ratio of 10:1 of sterile to wild males was required to achieve eradication in a central area of 300 km2. In marginal habitats, insecticide-impregnated targets were found adequate to control the tsetse population. The targets were also efficient as barriers to prevent reinvasion of the area. The combined effect of removal trapping and sterile male release is expected to eradicate G. p. palpalis from the entire study area.
Polymorphism in the rates of meiotic drive acting on the B-chromosome of Myrmeleotettix maculatus
4472Shaw, MWH, G. M.; Anderson, D. A., Heredity, 55:61-68. 1985-01-10 00:00:00.
A survey of all the available data on meiotic transmission rates in M. maculatus suggests that a polymorphism in female transmission rate exists in most natural populations. Differences in the frequency of the types or in the transmission rates they manifest may exist between populations or over time, but the evidence is not compelling. The data on males are also equivocal, especially because the environment may affect male transmission rate. We suggest that the polymorphism in female rates may demonstrate the selective equilibrium between the B and the genome in which it exists.
Genotypes suppressing meiotic drive of a B-chromosome in the mealybug, Pseudococcus obscurus
4471Nur, UB, B. L. H., Genetics, 110:73-92. 1985-01-09 00:00:00.
The rate of transmission (k) of a supernumerary B chromosome in male mealybugs is shown tq depend strongly on the chromosome set of materpal origin. When both parents came from an isofemale line in which the frequency of the B chromosome increased rapidly and stabilized at a mean of more than 4.0 B chromosomes per individual, was 0,92 and 0.95 in two series of crosses. However, when the female parent came from one of two isofemale lines in which the frequency of the B chromosome decreased from 2.0 to 0 in a few generations, R ranged from 0.53 to 0.78. The high ks, which represent a strong meiotic drive, are apparently responsible for the observed increase in the frequency of the B chromosome in several lines from a mean of about 0.5 to more than 4.0 in about 20 generations. The rapid loss of the B chromosome in other lines is attributed to genetic factors which caused the reduction in the rate of transmission qf the B chromosome.
Sex-chromosome meiotic drive in Drosophila melanogaster males
4474McKee, B, Genetics, 106:403-422. 1984-01-12 00:00:00.
In Drosophila melanogaster males, deficiency for X heterochromatin causes high X-Y nondisjunction and skewed sex chromosome segregation ratios (meiotic drive). Y and XY classes are recovered poorly because of sperm dysfunction. In this study it was found that X heterochromatic deficiencies disrupt recovery not only of the Y chromosome but also of the X and autosomes, that; both heterochromatic and euchromatic regions of chromosomes are affected and that the "sensitivity" of a chromosome to meiotic drive is a function of its length. Two models to explain these results are considered. One is a competitive model that proposes that all chromosomes must compete for a scarce chromosome-binding material in Xh- males. The failure to observe competitive interactions among chromosome recovery probabilities rules out this model. The second is a pairing model which holds that normal spermiogenesis requires X-Y pairing at special heterochromatic pairing sites. Unsaturated pairing sites become gametic lethals. This model fails to account for autosomal sensitivity to meiotic drive. It is also contradicted by evidence that saturation of Y-pairing sites fails to suppress meiotic drive in Xh- males and that extra X-pairing sites in an otherwise normal male do not induce drive. It is argued that meiotic drive results from separation of X euchromatin from X heterochromatin.
Integration of insect sterility and insecticides for control of Glossina morsitans morsitans Westwood (Diptera: Glossinidae) in Tanzania. IV. Application of endosulfan as an aerosol prior to release of sterile males
26520D. L. Williamson, D. A. Dame, C. W. Lee, D. B. Gates and P. E. Cobb, Bulletin of Entomological Research, 73:383-389. 1983-07-07 13:20:11.
As part of a programme to test the sterile insect technique against Glossina morsitans morsitans Westw. in Tanzania, two aerial applications of endosulfan were applied to a 195-km2 test area. The applications were made with a 28-day interval to provide an initial reduction in the target species prior to the release of sterile males. A Cessna 310 aircraft equipped with a rotary atomiser and operating at night was used to apply the insecticide at a dosage of about 20 g/ha. Flyround surveys within 48 h following the spraying operations indicated that a 100% reduction of G. m. morsitans adults was achieved in both applications, while G. pallidipes Aust. was reduced by 91 5% in the first and 100% in the second.
The fate of autosomeal modifiers of the sex-ratio trait in Drosophila and other sex-linked meiotic drive systems.
4475Wu, CI, Theoretical Population Biology, 24:107-120. 1983-01-13 00:00:00.
A model is proposed to analyze the behavior of autosomal suppressor modifiers of "Sex-Ratio" meiotic drive in drosophila. These modifiers, if neutral in fitness, are expected to increase because they tend to be associated with the rare sex (males). However, selection operating on the sex-linked drive locus will sometimes act against autosomal modifiers as well because the two loci are always in gametic phase disequilibrium. Conditions under which modifiers will not increase are presented in terms of the relative fitness of the sex-linked drive locus. To prevent the increase of modifiers, the fitness of Sex-Ratio males relative to Standard males has to be no greater than 0.3 and there has to be overdominance in females. This model integrates findings from the search for modifiers and results from the measurement of fitness.
Control of tsetse flies, Glossina spp.
26683D. A. Dame and A. M. Jordan, Advances in Veterinary Science and Comparative Medicine, 25:101-119. 1981-07-18 13:09:37.
Studies of SIT in Zimbabwe with releases of chemosterilized G. m. morsitans (Dame and Schmidt, 1970) demonstrated the feasibility of the methodology used both in the laboratory and in the field. Subsequent trials were recently completed in Tanzania, where laboratory bred sterile males were released into the natural breeding areas of a population of flies that had been partially suppressed by two aerial applications of endosulfan. Over a quarter of a million irradiated insects were released to control the G. m. morsitans population on a 195-km2 cattle ranch. The flies proved to be fully competitive andeffective. If it had been possible to isolate the plot from immigrating tsetse, the natural population on the ranch would probably have beep eliminated with a substantially lower number of flies than was necV essary to maintain the prolonged 90% level of control that was achieved (Dame et al., 1980). In Upper Volta, similar advances werd made with sterile G. p. gambiensis, bred in the laboratory and released in linear riverine habitats. Glossina p. gambiensis was eradicated from an 11-km section of the experimental plot (Cuisance et al., 1980)/ These accomplishments were completed after extensive study in Chad/ the Central African Republic, and Upper Volta.
Meiotic drive at the D(MD) locus and fertility in the mosquito, Aedes aegypti (L)
4479Youngson, JW, H. M.; Wood, R. J., Genetica, 54:335-340. 1981-01-17 00:00:00.
The Distorter gene D in Aedes aegypti shows meiotic drive when associated with the male determining M gene, causing sex ratio distortion in favour of males. The fertility of Distorter (MD /ms) and normal (M/m-) males has been compared after mating them to a series of 20 females at daily intervals. ; Males of each genotype inseminated up to 13 fe. males (mean 8.0 - 9.0). The major difference was in the significantly greater number of inviable eggs produced by females mated to Distorter males. It is postulated that these eggs were fertilised by abnormal spermatozoa. Females mated to Distorter males also produced significantly greater numbers of shrivelled i.e. unfertilised eggs, indicating a lower density of effective spermatozoa.; The difference in percentage hatch from the two matings was small, indicating that spermatozoa were produced in superabundance so that the overall fertility of Distorter males was not greatly reduced.
A 2-locus model for polymorphism for sex-linked meiotic drive modifiers with possible applications to Aedes aegypti
4478Maffi, GJ, S. D., Theoretical Population Biology, 19:19-36. 1981-01-16 00:00:00.
A two-locus model is presented which shows the possibility of maintaining a polymorphism for modifiers of sex-linked meiotic drive in the absence of fitness differences. The model is very similar to the situation actually found in some laboratory strains of the mosquito Aedes aegypti. The existence of a stable polymorphism usually requires sufficiently loose linkage between the two loci.
Experimental population-genetics of meiotic drive systems .3: Neutralization of sex-ratio distortion in Drosophila through sex-chromosome aneuploidy
4477Lyttle, TW, Genetics, 98:317-334. 1981-01-15 00:00:00.
Laboratory populations of Drosophila melanogaster were challenged by; pseudo-Y drive, which mimics true Y-chromosome meiotic drive through the; incorporation of Segregation Distorter (SD) in a T(Y;2) complex. This causes; extreme sex-ratio distrotion and can ultimately lead to population extinction.; Populations normally respond by the gradual accumulation of drive suppressors,; and this reduction in strength of distortion allows the sex ratio to move; closer to the optimal value of 1:l. One population monitored, however, was; rapidly able to neutralize the effects of sex-ratio distortion by the accumulation; of sex-chromosome aneuploids (XXY, XYY) . This apparently occurs because; XX-bearing eggs, produced in relatively high numbers (-4%) by XXY; genotypes, become the main population source of females under strong Ychromosome; drive. Computer simulation for a discrete generation model incorporating; random mating with differences in fitness and segregation permits; several predictions that can be compared to the data. First, sex-chromosome; aneuploids should rapidly attain equilibrium, while stabilizing the population; at -60% males. This sex ratio should be roughly independent of the strength; of the meiotic drive. Moreover, conditions favoring the accumulation of drive; suppressors (e.g., weak distortion, slow population extinction) are insufficient; for maintaining aneuploidy, while conditions favoring aneuploidy (e.g., strong; distortion, low production of females) lead to population extinction before drive; suppressors can accumulate. Thus, the different mechanisms for neutralizing; sex-ratio distortion are complementary. In addition, Y drive and sex-chromosome; aneuploidy are potentially co-adaptive, since under some conditions; neither will survive alone. Finally, these results suggest the possibility that; genetic variants promoting sex-chromosome nondisjunction may have a selective; advantage in natural populations faced with sex-ratio distortion.
Experimental population-genetics of meiotic drive systems .2: Accumulation of genetic modifiers of Segregation Distorter (SD) in laboratory populations
4482Lyttle, TW, Genetics, 91:339-357. 1979-01-20 00:00:00.
The accumulation of modifiers of the meiotic-drive locus Segregation; Distorter (SD) in Drosophila melanogaster was monitored by measuring the; changes in the mean and variance of drive strength (in terms of “make” value); that occur in laboratory populations when SD and SD+ chromosomes are in; direct competition. The particular SD lines used are T(Y;Z),SD translocations; showing pseudo-Y drive. Four sets of population cages were analyzed. Two sets; were monitored for changes in SD fitness and drive strength (presumed to be; positively correlated) and analyzed for the presence of autosomal dominant; or X-linked modifiers after long periods of time. The remaining two sets were; made up of cages either made isogenic or variable for background genetic; material, and these were used to test whether the rate of accumulation of; modifiers was dependent on initial genetic variability.-Contrary to previous; studies in which most suppression of SD action could apparently be attributed; to a few dominantly acting modifiers of large effect, the conclusion here is; that laboratory populations that are initially free of such major dominant loci; evolve to suppress SD action by accumulating polygenic, recessive modifiers,; each of small effect, and that much of the required genetic variability can be; generated a!e novo by mutation. Possible explanations for these seemingly incompatible results and the evolutionary implications for SD are considered.
Sex-ratio trait in Drosophila pseudoobscura – Fertility relations of males and meiotic drive.
4483Beckenbach, AT, American Naturalist, 112:97-117. 1978-01-21 00:00:00.
In the early analysis of the "sex-ratio" polymorphism (SR) of Drosophila pseudoobscura, complete meiotic drive was assumed, and study centered on the nature of the selective forces opposing its spread. Policansky and Ellison (1970) found that the mechanism of SR involved the degeneration of half the spermatids during spermatogenesis. They suggested that little or no drive may be expressed due to a fertility deficiency of SR males. Thus little or no selection is required to balance the drive. I report studies conducted to determine the conditions under which either of these alternatives might hold. Virgin females were mated once to either SR or ST (standard) males aged as virgins for 3 days, and their fecundities were determined by daily egg counts. No differences were found between the two groups in either daily egg production or egg-to-adult survival of the progenies. Only females maintained with males throughout the experiment were clearly superior in these parameters. No fertility differences between SR and ST males are unconditional. Fertilities of males aged for varying lengths of time as virgins were determined by mating them to as many virgin females as they would inseminate in a brief span of time. Time periods ranged from 3 to 8 h, depending on the ages of the males. Fertility of the SR males was lower than that of ST males of the same age for males aged 20-33 h from eclosion. Differences in 4-day-old males were not so clear. When 4-day-old males which had depleted their stores of sperm by repeated matings were retested after 12 h of rest, SR males again showed lower fertility than ST males. The fertility reduction of SR males occurs only during the first few days as adults or after repeated matings. The effect of different degrees of insemination on the pattern of production of fertile eggs was examined by mating virgin females to males which were either virgin (heavy insemination) or with seminal vesicles partially depleted by three previous matings (light insemination). No differences in either fecundity or hatchability between the groups were observed early in the reproductive period, but the hatchability of the eggs produced by the lightly inseminated females declined sooner than that of the heavily inseminated group. This response would minimize the populational consequences of fertility differences in males unless the females remate. It is suggested that the conditional fertility differences between SR and ST males are of little consequence until the females remate. Depending on the time of remating, there is potentially a wide range in the amount of meiotic drive expressed.
Transporting marker gene re (red eye) into a laboratory cage population of Aedes aegypti (Diptera Culicidae), using meiotic drive at MD locus
4486Wood, RJC, L. M.; Hamilton, A.; Whitelaw, A., Journal of Medical Entomology, 14:461-464. 1978-01-04 00:00:00.
An attempt has.been made to use the meiotic drive gene MD to transport a marker re (red eye) into a laboaratory population of the mosquito Aedes aegypti. The experiment produced an increase in re frequency, but also indicated that this gene has unexpectedly high fitness in the laboratory. The need for field estimates of fitness is indicated.
Sex ratio distortion caused by meiotic drive in a mosquito Culex pipiens
4485Sweeny, TLB, A. R., Genetics, 88:427-446. 1978-01-03 00:00:00.
A genetic factor, distorter (d), has been discovered that upsets the normal sex ratio of 1 : 1 and results in a large excess of males in Culex pipiens. The effect can be explained by a sex-linked, recessive gene. Males homozygous for the gene (Md/md) produce few female offspring; the effect is not due to postzygotic mortality. During the first meiotic division in spermatogenesis, the shortest chromosome pair, which, according to JOST and LAVEN (1971), is associated with sex determination, can be seen to be abnormal. In a high proportion of spermatocysts, one of the dyads of the shortest bivalent fragments, and the pieces are distributed irregularly to the daughter cells. It is believed that the female-determining chromosomes fragment. This would give rise to an excess of male-determining sperm. The possible usefulness of this factor for control or for experimental purposes is discussed.
Resistance to meiotic drive at MD locus in an Indian wild population of Aedes aegypti
4488Suguna, SGW, R. J.; Curtis, C. F.; Whitelaw, A.; Kazmi, S. J., Genetical Research, 29:123-132. 1977-01-06 00:00:00.
Females from an Indian wild population of Aedes aegypti were crossed to males carrying the sex ratio distorter factor MB which shows meiotic drive. Progenies from ¥1 males were tested for sex ratio distortion, i.e. the chromosomes from the wild females were screened for their resistance to the action of M°. The distribution of sex ratio in the progenies of different ¥1 males indicated a polymorphism in the wild population for resistant and sensitive variants of the X chromosome. Seven discrete categories of X appear to exist, associated with sex ratios ranging from 50 % $ to less than 1'25 % $. The overall level of resistance varied slightly but significantly in different parts of a town. The results are discussed in relation to the use of sex ratio distortion for genetic control of mosquitoes.
Experimental population-genetics of meiotic drive systems .1: Pseudo-Y chromosomal drive as a means of eliminating cage populations of Drosophila melanogaster
4487Lyttle, TW, Genetics, 86:413-445. 1977-01-05 00:00:00.
The experimental population genetics of Y-chromosome drive in Drosophila; melanogasier is approximated by studying the behavior of T(Y;S),SD lines.; These exhibit “pseudo-Y” drive through the effective coupling of the Y chromosome; to the second chromosome meiotic drive locus, Segregation distorter; (SD). T(Y;S),SD males consequently produce only male offspring. When; such lines are allowed to compete against structurally normal SD+ flies in; population cages, T(Y;S),SD males increase in frequency according to the; dynamics of a simple haploid selection model until the cage population is; eliminated as a result of a deficiency in the number of adult females. Cage; population extinction generally occurs within about seven generatiomSeveral; conclusions can be drawn from these competition cage studies:; (1) Fitness estimates for the T(Y;Z),SD lines (relative to SD+) are generally; in the range of 2-4, and these values are corroborated by; independent estimates derived from studies of migration-selection; equilibrium.; (2) Fitness estimates are unaffected by cage replication, sample time, or; the starting frequency of T(Y;Z),SD males, indicating that data from; diverse cages can be legitimately pooled to give an overall fitness; estimate.; (3) Partitioning of the T(Y;S),SD fitnesses into components of viability,; fertility, and frequency of alternate segregation (Y + SD from; X+SD+) suggests that most of the T(Y;S),SD advantage derives; from the latter two components. Improvements in the system might; involve increasing both the viability and the alternate segregation to; increase the total fitness.; While pseudo-Y drive operates quite effectively against laboratory stocks,; it is less successful in eliminating wild-type populations which are already; segregating for suppressors of SD action. This observation suggests that further
Between family variation in sex-ratio in Trinidad (T-30) strain of Aedes-aegypti (L) indicating differences in sensitivity to meiotic drive gene MD
4494Wood, RJ, Genetica, 46:345-361. 1976-01-12 00:00:00.
Sex ratio in the Trinidad (T-30) strain of Aedes aegypti has remained constant at around 43%? during seventeen years of laboratory culture. The divergence from 50% is due to meiotic drive by the MD gene on the Y chromosome. The driving Y chromosome gives a much more distorted sex ratio (mean = 5.7%?) when coupled with the highly sensitive X chromosomes from strain 64. This was demonstrated in all of 98 families tested, indicating that all or most of the Y chromosomes in T-30 carry the MD gene. Consequently the low level of sex ratio distortion in T-30 must be due to resistance to MD.; ; Crosses made within T-30 demonstrated wide differences in sex ratio between families, depending on the sensitivity of the male parent's X chromosome to MD. However, sex ratios were not continuously variable but fell within fairly discrete categories. Thus, X chromosomes could be classified according to the modal sex ratios associated with them: ms3 (12.5%?), ms2 (32.5%?), ms1 (40%?), mr1 (47.5%?) mr2 (57.5%?).; ; The different sex ratio categories were more discrete in the families of sib matings than from random matings, suggesting the possibility of background modification of what is essentially a balanced polymorphism. Evidence is presented suggesting that the polymorphism could be due to interaction at two loci. A further X variant, ms4 (<10%?) characterised strain 64 but was absent from T-30.; ; A comparison of fertility between the different sex ratio categories in T-30 established that sex ratio distortion was not caused by differential mortality after fertilisation.
Evidence for autosomal meiotic drive in the butterfly Danaus chrysippus L.
4492Smith, DAS, Heredity, 36:139-142. 1976-01-10 00:00:00.
Danaus chrysippus (Danaidae) in East Africa is highly polymorphic for colour, the genetic control of which resides at three loci. The B locus has two alleles, B giving a nutbrown ground colour and bb orange on both fore and hindwings. The C locus determines forewing pattern: there are two alleles, C giving a wing uniformly coloured except for a black margin (form dorippus) and cc a large black apical area traversed by a row of white subapical spots (form ae&yptius = form chrysippus of my earlier papers). Heterozygotes (Cc) are basically dorippus but are often phenotypically distinct in showing the "aegyptius" subapical spots on the underside of the forewing. The B and C loci are closely linked (Smith, 1975a). The A locus has a recessive allele a the homozygous possessor of which has a large white patch on the hindwing (form alcippus when combined with the aegyptius forewing and form albinus with the dorippus forewing). The A locus probably assorts independently from the B and C loci (Clarke, Sheppard and Smith, 1973; Smith, 1975a). All-female broods commonly occur in D. chrysippus. These probably result when a Y-linked gene D causes meiotic drive for the Y chromosome so that it always enters the secondary oocyte at the first meiotic division in the female. Females from all-female broods usually themselves produce allfemale broods but a switch to bisexual broods can occur and seems to depend on the acquisition of a dominant autosomal suppressor gene S from the maternal male grandparent. The S locus is probably closely linked with the C locus (Smith, 1975b).
Cytogenetic analysis of meiotic drive in mosquito, Aedes aegypti
4491Newton, MEW, R. J.; Southern, D. I., Genetica, 46:297-318. 1976-01-09 00:00:00.
Meiotic drive in Aedes aegypti (L.) is shown by a Giemsa C-banding technique to be associated with. preferential isochromatid breakage of the X chromosome during male meiosis. These breaks remain open at least until anaphase-I and, since the range of cells affected is proportional to the sensitivity of the X chromosome to the Distorter gene, it is argued that they are directly related to the decreased number of spermatozoa found in distorting males. This reduction is considered to be attributable to the degeneration of more X- than Y-bearing spermatids but it is probable that some non-functional X-bearing spermatozoa are also produced. Chromosome breakage is almost completely confined to four sites, two adjacent to the centromere, one just proximal to the intercalary band and another about the centre of the unbanded arm. Although the first three of these lie within a region in which crossing-over does not take place, fragmentation occurs more frequently in a chiasmate arm than in one devoid of chromatid exchange.
Meiotic drive for B-chromosomes in primary oocytes of Myrmeleotettix maculatus (Orthoptera-Acrididae)
4489Hewitt, GM, Chromosoma, 56:381-391. 1976-01-07 00:00:00.
Using a modified technique which allowed observation of chromosome orientation in the primary oocyte of grasshoppers at the onset of anaphase, it has been possible to establish that the B-chromosome is distributed preferentially on the egg side of the metaphase plate rather than the polar body side. The frequency of this preferential orientation matches very closely the level of preferential transmission determined from breeding experiments using individuals from the same population. The spindle is asymmetrical in the primary oocyte of this species, and a possible explanation of the meiotic drive is proposed as a result of the conical shape of nucleoplasm surrounding this spindle. The autosomal chiasma frequency of these females is generally lower than comparable males and is increased by the presence of B chromosomes; but the chiasma frequencies of the sexes respond differently to the addition of 1 and 2 B-chromosomes.
Population genetics of modifiers of meiotic drive 4: Evolution of sex-ratio distortion
4497Thomson, GJF, M. W., Theoretical Population Biology, 8:202-211. 1975-01-15 00:00:00.
A model for the evolution of the sex-ratio meiotic drive system in Drosophila is proposed and analyzed. The model incorporates drive and altered fertility genetic modification The condition change in the sex-ratio of the modifying distortion overcome any relative of meiotic in the carriers of the modified sex-ratio chromosomes. that a sex-ratio modifying chromosome increase is that the relative fertility chromosome. When no fertility model predicts that any increase in distortion differences are involved, of the sex ratio will be favored. loss in carriers the
Sex-chromosome meiotic drive systems in Drosophila melanogaster .1: Abnormal spermatid development in males with a heterochromatin-deficient X-chromosome (sc4sc8)
4496Peacock, WJM, G. L. G.; Goodchild, D. J., Genetics, 79:613-634. 1975-01-14 00:00:00.
The meiotic drive characteristics of the In(1)sc4Lsc8R/Y system have been examined by genetic analysis and by light and electron microscopy. sc4sc8/Y males show a direct correlation between nondisjunction frequency and meiotic drive. Temperature-shift experiments reveal that the temperature-sensitive period for nondisjunction is at meiosis, whereas that for meiotic drive has both meiotic and post-meiotic components. Cytological analyses in the light and electron microscopes reveal failures in spermiogenesis in the testes of sc4sc8 males. The extent of abnormal spermatid development increases as nondisjunction becomes more extreme.
Sex-ration, meiotic drive, and group selectin in Drosophila pseudoobscura
4498Policansky, D, American Naturalist, 108:75-90. 1974-01-16 00:00:00.
Sex ratio (SR) is a widespread genetic condition of the X-chromosome in Drosophila species which causes males to produce progenies consisting almost entirely of females. Results of samples from natural populations of Drosophila pseudoobscura and results of some laboratory experiments indicate that SR males produce only about half as many sperm as normal (ST) males; because of this deficiency, SR males are able to fertilize only about half as many eggs as ST males. These results explain the observed equilibria of frequencies of SR in natural populations, and suggest that, at least in the case of D. pseudoobscura, male fertility may be partly limited by the number of sperm males can produce.
Lâchers de mâles stériles de Glossina tachinoides West. dans un gîte naturel de faible densité Bas-Logone, Cameroun
26657D. Cuisance and J. Itard, Revue d’élevage et de médecine vétérinaire des pays tropicaux, 26:405-422. 1973-04-01 06:33:32.
Des mâles adultes de G. tachinoides, élevés à Maisons-Alfort et irradiés entre 7 600 et 10 650 rads à Saclay (France), ont été expédiés chaque semaine par avion à N'Djamena (Tchad) entre février et juin 1973, pour être, après marquage, lâchés en plusieurs points d'un gîte naturel, sur les berges du Logone. Par suite d'une sécheresse exceptionnelle, la population de mouches sauvages dans ce gîte étant de faible densité, la proportion de mâles stériles lâchés a pu être élevée, le rapport mâles stériles/mâles sauvages étant, en moyenne, pendant toute la période des lâchers, de 2,8/I. La longévité moyenne des mâles stériles a été de 6,5 jours contre 8 jours pour les mâles sauvages. Les mâles stériles ont eu un comportement identique à celui des mâles sauvages. Bien qu'un autre gîte, qui servait de témoin, ait été fortement dégradé par l'homme et les animaux, ce qui n'a pas permis d'apprécier exactement l'effet des lâchers de mâles stériles dans le gîte d'expérience, on estime cependant qu'à partir de la mi-mars, la chute de densité de la population sauvage est en grande partie due à la présence des mâles stériles, ce qui semble confirmé par l'observation de femelles sauvages capturées dans les deux gîtes: 69 p. 100 des femelles capturées dans le gîte d'expérience n'ont eu aucune descendance au cours de trois semaines d'observation, alors que toutes les femelles du gîte témoin ont produit une pupe dans les huit jours suivant leur capture
Comportement de mâles stériles de Glossina tachinoides West. lâchés dans les conditions naturelles – environs de Fort-Lamy (Tchad). I. Transport, lâchers, rythme d’activité, action sur la population sauvage
26645D. Cuisance and J. Itard, Revue d'élevage et de médecine vétérinaire des pays tropicaux, 26:55-76. 1973-01-01 15:42:14.
Glossina tachinoides adult males, bred and irradiated with 15,500 rads in Maisons-Alfort (France) were dispatched by air-mail to Fort-Lamy (Chad) between February and May of 1972, in order to be released, after marking, in a natural area of Cameroon side of the Chari river. In this first part, the authors analyse the consequences of breeding-irradiation-transport-handling ” factors on sterile males behaviour and activity rhythm. The too small a quantity of sterile males is essentially the cause of the absence of any measurable effect on naturel population evolution.
Multiple meiotic drive systems in Drosophila melanogaster male
4499Miklos, GLGY, A. F.; Peacock, W. J., Genetics, 72:105-115. 1972-01-17 00:00:00.
The behaviour of two "meiotic drive" systems, Segregation-Distorter (SD) and the sex chromosome sc4sc8 has been examined in the same meiocyte. It has been found that the two systems interact in a specific way. When the distorting effects of SD and sc4sc8 are against each other, there is no detectable interaction. Each system is apparently oblivious to the presence of the other, gametes being produced according to independence expectations. However when the affected chromosomes are at the same meiotic pole an interaction occurs; the survival probability of the gamete containing both distorted chromosomal products is increased, rather than being decreased by the combined action of two systems.
The Sterile-Male Technique Against Tsetse Flies, Glossina Spp
26213D. A. Dame and C. H. Schmidt, 16, 24-30. 1970-03-16 15:05:33.
Simpson (1958) discussed the relationship between the biological characteristics of the genus Glossina and the use of the sterile-male technique in the control of this vector of trypanosomiasis, as did Knipling in an informal report in 1963 on Practical Role of the Sterility Principle for Tsetse Fly Eradication in WHO/Vector Control/27. Knipling estimated that an initial overflooding ratio of sterile to wild males of 3: 1 with successively smaller releases could eradicate a low-density population of flies in 12 months (Table 1) at a cost of about 125/mile2, even if the sterilized males cost as much as 5 cents each. With larger populations, other methods would have to be used to reduce the density before the releases of sterile males. Also, Knipling (1964) emphasized the economic advantage that would be gained by reduction in the total number of sterile males required if their release were preceded by a single application of a nonpersistent insecticide which would eliminate most of the adult population. When populations cover a wide area, simultaneous treatment of the entire infested area might not be feasible. A more realistic approach (Table 2) could be to systemically expand small control areas along a common front (Dame 1968).
Meiotic drive in natural populations of Drosophila melanogaster 9: Suppressors of segregation distorter in wild populations
4500Hartl, DL, Canadian Journal of Genetics and Cytology, 12:594-600. 1970-01-18 00:00:00.
A population of Drosophila melanogaster in Madison, Wisconsin, has been screened for suppressors of segregation distorter (SD), an autosomal meiotic drive element found in the same population. Three kinds of suppressors were tested for: (1) Y-linked suppressors, none were found, (2) X-linked suppressors, whose frequency was found to be 85%, and (3) autosomal dominant suppressors, which occur in 45% of autosome complements.The frequency of X-linked suppressors is comparable to that found in a Japanese population; autosomal suppressors are much more frequent in Madison than in Japan (Katoaka, 1967). The similarity in the frequency of sex-linked suppressors may result from the meiotic drive shown by the suppressor-X itself; the difference in the frequency of autosomal dominant suppressors is possibly related to a higher frequency of SD itself in the Madison population.
Meiotic drive and visible polarity in Drosophila spermatocytes
4504Yanders, AFB, J. G.; Peacock, W. J.; Goodchild, D. J., Genetics, 59:245-253. 1968-01-02 00:00:00.
The model for meiotic drive presented by PEACOCK and ERICKSON (1965) demands that an intracellular differentiation exists at the time of the first meiotic division in spermatocytes. As a result of this differentiation, one of the spindle poles at anaphase I will lead to the formation of two functional sperm, while the other pole will yield two nonfunctional sperm. This model can be used to explain cases of meiotic drive, such as Segregation-Distorter (SD) ( SANDLER, HIRAIZUMI, and SANDLER 1959), if one member of a chromosome pair moves to the functional pole in a nonrandom fashion, and is thereby preferentially included in the functional gametes.
Genetic distortion of sex ratio in a mosquito Aedes aegypti
4505Hickey, WAC, G. B., Genetics, 53:1177-1196. 1966-01-03 00:00:00.
CRAIG, HICKEY and VANDEHEY (1960) reported that a hereditary factor transmitted by males was responsible for high male ratios in A. aegypti. This phenomenon was designated as male-producing or MP. Males from high maleproducing families produced a high proportion of males in their own progeny, regardless of the type of female to which they were crossed. This condition was not due to selective mortality, at least in postgametic stages. In 1960, nothing was known about the sex-determining mechanism in A. aegypti. In addition, the male-producing lines available for study were highly variable in expression. These factors hampered more precise analysis of the mechanism of inheritance of MP. The present work was initiated because new crosses with different strains gave more pronounced and predictable distortion of sex ratios. Earlier strains gave about 15 to 30% female, whereas present lines produce about 0 to 15% female. This paper presents an analysis of the mode of inheritance of MP. In addition, data suggesting the mechanism of action are included. Separate reports will be published elsewhere on ( 1 ) the distribution and behavior of MP in experimental populations and (2) the effect of environment on expression of MP. A more detailed account of some of this work is given by HICKEY (1965a, b). Nomenclature used ih these preliminary reports is superseded by that in the present work.
Meiotic drive in Drosophila involving chromosome breakage
4506Erickson, J, Genetics, 51:555-571. 1965-01-04 00:00:00.
In ordinary genetic systems the members of a pair of unlike alleles, or of a pair of unlike chromosomes, are recovered in equal numbers among the off spring, barring complications affecting viability. Contrary to this expectation, in a number of studies it has been found that one allele or chromosome is recovered in significantly more than 50 percent of the functional gametes. The time and mode of the action resulting in inequality varies; where these phenomena result from events of the meiotic process they are known as instances of meiotic drive (SANDLER and NOVITSKI 1957). The case described herein was isolated from a chronically irradiated population (NOVITSKI and HANKS 1961), and was referred to as “29G” previously (HANKS 1961; ERICKSON and HANKS 1961). HANKS (1964) has renamed the line “RD”, referring to a disruption in recovery of the Y chromosome. which gives rise to a high-female sex ratio in the off spring of RD males.
Aanalysis of case of meiotic drive in Drosophila melanogaster
4507Hanks, GD, Genetics, 50:123-130. 1964-01-05 00:00:00.
IN the past ten years there has been a renewed interest in the abnormal recovery of chromosomes after meiosis; see for example DUNN (1953); NOVITSKI and SANDLER (1957) ; SANDLER and NOVITSKI ( 1957) ; LINDSLEY and SANDLER (1958); NOVITSKI and HANKS (1961); and MAGUIRE (1963). When the two types of gametes from a heterozygote are recovered with unequal frequency because of a meiotic mechanism the force resulting is called meiotic drive (SANDLER and NOVITSKI 1957). Such a force is capable of altering allele frequencies in a population, and thus the evolutionary consequences are potentially important; this has been discussed in detail by DUNN (1953) and SANDLER and NOVITSKI (1957). The case analyzed here was found by testing chromosomes from population cages maintained by WALLACE atCold Spring Harbor which were subjected to low intensity radiation for over 200 generations (WALLACE 1956). Earlier studies have indicated that the case here analyzed does not produce its effect by zygotic mortality, is manifested only in the male, and is greatly altered by temperature changes during the period of meiosis in the male (NOVITSKI and HANKS 1961; ERICKSON and HANKS 1961). This paper presents the genetic analysis of this case showing the extent to which its effect may be modified by substituting different sex chromosomes and autosomes.
Meiotic drive in natural populations of Drosophila melanogaster .7. Conditional segregation distortion – a possible nonallelic conversion
4512Sandler, LH, Y., Genetics, 46:585-604. 1961-01-10 00:00:00.
Males, heterozygous for the Segregation-distorter (SD) allele (located in or near the centromeric heterochromatin of the right arm of chromosome 11) and a standard tester second chromosome, regularly produce a preponderance of functional SD-bearing sperm ( SANDLER, HIRAIZUMI and SANDLER 1959). Segregation in heterozygous SD females, on the other hand, is always normal. It has been found, however, that, for certain SD lines, if the SD-bearing chromosome is inherited from the female parent, then, in a fraction of F, male sibships, only one half of the heterozygous SD sons exhibit the phenomenon of segregationdistortion; in the other half of the sons, segregation is normal. In the following generation, all of the males exhibit abnormal ratios irrespective of whether or not their father showed an abnormal ratio. Those females that produce sons. only one half of which distort, are referred to as conditioned; the phenomenon is termed conditional distortion ( SANDLER and HIRAIZUMI 1959)
Meiotic drive in natural populations of Drosophila melanogaster .8. A heritable aging effect on phenomenon of segregation distortion
4511Sandler, LH, Y., Canadian Journal of Genetics and Cytology, 3:34-46. 1961-01-09 00:00:00.
Second chromosomes have been found in natural populations of Drosophila melanogaster that contain an abnormal centromere region which conditions a highly aberrant segregation ratio in heterozygous males (Sandler, Hiraizumi, and Sandler, 1959). In particular, when a chromosome carrying this abnormal region (symbolized SD for Segregation-distorter) is made heterozygous with a normal second chronlosome (routinely a standard tester chromosome marked by the recessives cn and bw) in males, and backcrossed to homozygous cn bw females, 90 per cent or more of the F1 receive the SD-bearing second chromosome. These abnormal segregation ratios are not accompanied by egg mortality. It has now, been found that as heterozygous SD males are aged, the segregation ratios become less abnormal. When, moreover, young sons of aged fathers are examined, it is found that they too exhibit less extreme segregation ratios. Indeed, changes in the segregation ratio induced by aging may persist in selected, males for at least five generations and possibly indefinitely. The evidence demonstrating a heritable aging effect and a consideration of certain other questions relevant to the aging phenomenon are presented below.
Analysis of irradiated Drosophila populations for meiotic drive
4510Novitski, EH, G. D., Nature, 190:989-990. 1961-01-08 00:00:00.
The existence of chromosomes or alleles that are represented in the gametes of a heterozygote with a frequency greater than the expected 50 percent is now well established for a variety of species. The immediate population result of introducing such a chromosome or allele must be a sharp increase in its frequency, alon with any other genes associated by linkage, independent of or, indeed, in spite of, their phenotypic effects. For this reason such phenomena have been referred to as cases of 'drive' and, more specifically, as 'meiotic drive' when the basis is found in some aberration of meiosis. Such instances would seem to provide an unparalleled opportunity for the study of population dynamics, for example, the efficacy of response of natural selection to unfavourable genes. It seemed worth while, therefore, to determine whether such chromosomes or alleles characterized by drive might be induced in the laboratory.
Meiotic drive in natural populations of Drosophila melanogaster .6: A preliminary report on presence of segregation-distortion in a Baja california population
4509Mange, EJ, American Naturalist, 95:87-96. 1961-01-07 00:00:00.
Meiotic drive is a term coined by Sandler and Novitski (1957) to describe; the situation whereby a heterozygote produces gametes containing an excess; of one allele, rather than the expected equality. As a consequence of such; aberrant segregations, gene frequencies within a population may be radically; altered; indeed, detrimental or lethal genes closely linked to the driven gene; may increase in frequency, thereby leading to a reduction in fitness or pos; sibly even to extinction of the population.; An instance of meiotic drive in Drosophila melanogaster, discovered by; Hiraizumi in a Madison, Wisconsin, population, has been reported by Sandler,; Hiraizumi and Sandler (1959). The phenomenon, termed segregation-distortion,; was found to depend upon a locus designated SD, which is located in the; centromeric heterochromatin of chromosome II. The phenomenon is ex; pressed in males only.; Since segregation-distortion was originally found in a natural population,; the question arose as to whether the phenomenon is of recent origin and; therefore localized in the vicinity of Madison, or well established and hence; widespread among natural populations of Drosophila melanogaster. There; fore, the screening of wild populations for SD (or for any other type of aber; rant segregation) was undertaken. In small samples from only thirteen popu; lations, SD has been detected in one Baja California population as well as; in three other rather widely separated Madison populations. This report will; be confined to establishing that the locus discovered in the southern Cape; region of Baja California (specifically, from Rancho La Burrera near the; west base of Sierra de La Laguna, and a Pleistocene lake relic, called; La Laguna, in the same range) is indeed SD.
Meiotic drive in natural populations of Drosophila melanogaster .4: Instability at the Segregation Distorter locus
4515Sandler, LH, Y., Genetics, 45:1269-1287. 1960-01-13 00:00:00.
In a collection of flies from a natural population of Drosophila melanogaster, several second chromosomes have been isolated that contain, in the centromere region .of chromosome 11, a locus (named segregation-distorter and symbolized SO) that conditions, in heterozygous males, a highly abnormal segregation ratio in favor of the SD-bearing chromosome. Experiments bearing on the cytogenetic basis of the phenomenon of segregation-distortion and on the formal genetics of the SD locus have been reported by SANDLER, HIRAIZUMI, and SANDLER (1959). and by SANDLER and HIRAIZUMI ( 1959).
Meiotic drive in natural-populations of Drosophila melanogaster 3: Populational implications of the Segregation-Distorter locus
4513Hiraizumi, YS, L.; Crow, J. E., Evolution, 14:433-444. 1960-01-11 00:00:00.
If, among the successful gametes frm heterozygotes, one allele is regularly included in more than half, it may increase in frequency even if it has a harmful effect. Unequal gamete production, when attributable to the mechanics of meiosis, has been called meiotic drive (Sandler and Novitski, 1957). An example is segregation-distortion in Drosophila melanogaster, the cytogenetic behavior of which has been reported by Sander, Hiraizumi and Sandler (1959) and Sandler and Hiraizumi (1959)
Meiotic drive in natural populations of Drosophila melanogaster 2. Genetic variation at the Segregation Distorter locus
4516Sandler, LH, Y., Proceedings of the National Academy of Sciences of the United States of America, 45:1412-1422. 1959-01-14 00:00:00.
It has now been found that the proportion of heterozygous SD males resulting from any given cross which exhibits segregation-distortion, and the amount of distortion that any particular male shows (the k value), varies widely depending upon the precise source and history of the SD-bearing and the SD+-bearing chromosomes in the heterozygotes being tested. It is the purpose of this report to present a general account of the kinds of variations in the behavior of SD which have been observed. More fully documented reports of each phase of the work are currently in preparation, and will be presented elsewhere. For this reason, extended discussion of these variations and comparable systems in other organisms has been omitted.
Experiments in the hybridisation of tsetse-flies (Glossina, Diptera) and the possibility of a new method of control.
6139F. L. Vanderplank, Transactions of the Royal Entomological Society of London, 98:1-18. 1947-01-02 21:38:18.
Hybridisation of Glossina morsitans Westwood, G. swynnertoni Austen and G. pallidipes Austen was attempted in order to discover(a) Whether the three could be regarded as distinct species or as sub-species of morsitans ; (b) Whether they would mate freely with one another, and if not by what means the three closely allied forms distinguished their own kind ; (c) Whether morsitans and swynnertoni would readily produce hybrid offspring, and if so, what proportion of females would do so, and what proportion of hybrids would be sterile ; (d) Finally, whether interference with one species by another could be used as a measure of control. I also wanted to explore other details including markings, colouration and nature of the genitalia of the hybrids, and whether these characters were constant or variable.
Tsetse hybrids
6145W. H. Potts, Nature, 154:606-607. 1944-11-11 21:48:03.
IN 1936 I attempted to cross various species of tsetse (Glossina) with the idea that, should they hybridize readily, and should the resultant hybrids prove sterile, this might be tried as a measure of control. Corson had already, in 1932, obtained three offspring from crosses between male G. swynnertoni and female G. morsitans; he suggested, however, that these might not be true hybrids, but the result of parthenogenesis (see further details in the accompanying communication by Mr. F. L. Vanderplank). I obtained a number of offspring from this and other crosses, but as a slight doubt arose as to whether they were authentic hybrids, the results were never published.
Hybridization between Glossina Species and Suggested New Method for Control of Certain Species of Tsetse
6142F. L. Vanderplank, Nature, 154:607-608. 1944-11-11 21:43:25.
Corson and Potts record crossing Glossina swynnertoni Aust. with G. morsitans Westwood. Corson crossed twelve female G. morsitans with male G. swynnertoni, of which only two females produced a total of three pupæ. All his females lived long enough for reproduction to take place. He records the offspring, all females, as being identical with pure-bred G. morsitans, and suggested parthenogenesis. Potts crossed both male G. morsitans with female G. swynnertoni and male G. swynnertoni with female G. morsitans (see accompanying communication by Mr. W. H. Potts).
On the possibility of a new method for the control of insect pests.
6157A. S. Serebrovskii, Zoologicheskiĭ zhurnal, 19:618-630 (in Russian). 1940-01-03 16:43:28.
ON THE POSSIBILITY OF A NEW METHOD FOR THE CONTROL OF INSECT PESTS. The new principle of insect control consists in disturbing the propagation of the pest population by means of translocations. It is well known that individuals heterozygous for some translocations usually form a portion of aneuploid gametes and give a more or less inviable aneuploid progeny. On releasing, therefore, a sufficient number of individuals with a chromosome set altered by. translocations into a wild population (with allogamous propagation), there will arise heterozygotes for translocations yielding a certain percentage of inviable offspring. Crosses inside this population will be similar to those between species with resulting sterility of hybrids. The theoretical analysis reveals that if a wild population is mixed in proportion 1:1 with some race containing only one translocation viable in homozygous condition and giving in heterozygotes 50% of aneuploid gametes, the reproduction of the population will be reduced by 43%. If several races with different allelic translocations are released the reduction of reproduction in the population can reach 75%, and if races with 4-5 independent translocations are used the reduction can attain 95%-99% and even more. A population consisting of races with different translocations cannot remain in balance. Those types of chromosomes which happened to be in minority are subjected to elimination. Yet this process of elimination will go on during many generations and thus the disturbance of reproduction will be protracted. By an additional releasing of eliminating race, this disturbance can be maintained permanently. Diverse variants of this method are possible, depending upon the biology and economic importance of injurious insects, the cost of breeding translocated races in laboratories, the difficulties of obtaining viable translocations, etc. It is possible, for instance, to release only males, a method in which there is evidently no danger at all. The present investigation is a purely theoretical one. For the purpose of verifying experimentally this idea work has been started with Musca domestica and Calandra granaria - two insects widely differing in their cytogenetics, ecology and the kind of damage caused.
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