Keywords: Sex distorter
Is a ‘selfish gene’ making a Utah family have twice as many boys as girls?
35478Ewen Callaway, Nature, 2026-02-27 18:24:37.
By sifting through an anonymized genealogy database, researchers have discovered a Utah family that has been having twice as many boys as girls for seven generations. It is the first clear evidence that humans might have ‘selfish genes’ that distort the sex ratio of offspring from roughly 50:50, the researchers argue in a preprint posted on bioRxiv earlier this month. The findings have not been peer-reviewed. Such sex ‘distorters’ have been discovered — and studied in great depth — in laboratory animals such as mice and flies, in which their effects can be detected through selective breeding. “If you look, more often than not, you find them,” says Nitin Phadnis, an evolutionary geneticist at the University of Utah in Salt Lake City, who co-led the study. Theoretical predictions suggest that sex distorters probably do exist in people as well, and that they could produce excesses of biological boys or girls at birth. But humans’ long generation times and low birth rates as well as ethical issues have made such genes — and other ‘selfish’ genetic elements , meaning that they bias their own transmission to future generations whether or not they improve an individual’s biological fitness — difficult to spot.
Synthetic biology approaches to generate temperature-sensitive alleles for the Sterile Insect Technique
35280Chun Yin Leung, Ernst A. Wimmer, Hassan M. M. Ahmed, Insect Science, 2025-11-03 11:22:09.
The Sterile Insect Technique (SIT) is an environmentally friendly, sustainable pest control approach, which uses large-scale releases of sterile insects to suppress or eradicate target populations through infertile matings. The efficiency of SIT is enhanced by male-only releases requiring genetic sexing strains (GSSs) that are classically based on selectable recessive visible markers or temperature-sensitive lethal (tsl) mutations and a rescue by a wild-type allele translocated to the male-determining chromosome. The transfer of identified or designed temperature-sensitive alleles might allow the generation of neoclassical GSSs in additional SIT target species. By using precise genome-editing tools, such as CRISPR/Cas, the creation of specific mutations in target genes and the integration of a wild-type copy is feasible without the introduction of foreign DNA. This might ease regulation of neoclassical GSSs, since they are not considered transgenic. However, integration and expression of genes at male-determining loci or chromosomes is not reliably established. Therefore, additional strategies to link temperature-sensitive phenotypes to female development are required, which could be achieved by targeting genes involved in dosage compensation or sex determination. To create temperature-sensitive alleles, rational protein design using advanced modeling and prediction tools to evaluate and tailor the effect of mutations on protein stability and temperature sensitivity can be used. In addition, emerging synthetic biology strategies such as temperature-inducible N-degrons or temperature-sensitive inteins provide powerful tools to generate temperature sensitivity. Such approaches should enable conditional control over proteins causing female lethality or sex conversion and therefore promise straightforward generic approaches to generate GSSs for male-only production in SIT target species.
Developing Y chromosome sex ratio distorters in the model insect Drosophila melanogaster
35259Yael Arien, Chen Zacharia, Elad Yonah, et al., bioRxiv, 2025-10-28 08:24:56.
CRISPR-Cas9 sex ratio distortion (SRD) systems can suppress insect populations by biasing progeny toward males, but realizing such systems requires reliable Cas9 expression from insect Y chromosomes. Here, we tested whether the spermatocyte-specific betaTub85D promoter can drive functional Cas9 expression when inserted on the Drosophila melanogaster Y chromosome. Using CRISPR-mediated homology-directed repair, we generated a Y-linked betaTub85D-Cas9-T2A-eGFP construct and compared its activity with an autosomal counterpart. Whereas autosomal betaTub85D-Cas9 induced strong male-biased sex ratios when paired with an X-poisoning gRNA, the Y-linked construct failed to distort sex ratios and exhibited approximately 2,000-fold reduction in Cas9 transcript abundance. Nonetheless, weak but detectable GFP fluorescence and Cas9 transcripts confirmed partial Y-linked promoter activity. These findings provide the first direct experimental evidence of meiotic sex chromosome inactivation (MSCI) acting on the Drosophila Y chromosome, revealing that meiotic promoters can remain weakly active despite strong repression. This work defines transcriptional limits of the Drosophila Y chromosome and informs the design of next-generation Y-linked gene drives for sustainable insect control.
The role of the transformer gene in sex determination and its employment in CRISPR/Cas9-based homing gene drive in the global fruit pest Drosophila suzukii
35185Dan Deng, Xueying Yi, Wen Wen, Liuqing He, Wei Peng, Insect Biochemistry and Molecular Biology, 184. 2025-09-29 08:45:13.
Sex determination of Diptera is established by the cascade genes such as transformer (tra), though the primary signals for sex determination differ among different insects. Here, we report the isolation, expression and function of tra gene in an invasive pest, Drosophila suzukii, and study the potential use of the D. suzukii tra (Dstra) gene in CRISPR/Cas9-based homing gene drive for genetic-based pest management. The Dstra gene is highly conserved in structure and has a sex-specific transcript. To test the function of this gene in sex determination, Dstra dsRNA was injected into embryos. Almost all XX embryos developed into masculinized phenotypic male adults with intersex morphology. Abnormal ovaries were revealed in XX pseudomales upon dissection. Based on the necessary role of Dstra for female development, we developed and evaluated a homing gene drive that targets Dstra in D. suzukii. The drive component consisting of multiplex Dstra single guide RNAs and Cas9 with Dsvasa promoter was introduced into the Dstra locus. Abnormal development of both the external genitalia and gonads was observed in G0 and G1 chromosomal female adults that expressed the male-specific doublesex (dsx) transcript. Interestingly, knocking out Dstra led to significantly reduced fertility in adults of corresponding sex and moderate transmission rates of the DsRed gene (63.54 %) were observed. Our results not only confirm the conserved function of the Dstra gene in sex determination, but also highlight the potential of sex conversion-based suppression gene-drive strategy targeting the Dstra gene in controlling of D. suzukii populations.
Leveraging Sex Determination Systems for Genetic Biocontrol of Dipteran Pests
35178Maxwell J. Scott, Zhijian Tu, Current Opinion in Insect Science, 2025-09-26 14:24:25.
Genetic biocontrol is an increasingly important way to suppress insect pest populations and to mitigate their economic and health impact. One key advantage is that it is species-specific as it relies on mating of released males with wild females to either suppress or modify populations. The latter is through rendering females incompetent at disease transmission. Sex separation is critical to ensure the efficiency of these control programs, and it is essential in the case of vector control to avoid releasing females that can transmit pathogens. Modern genetic methods provide the opportunity to target or manipulate components of the sex determination systems to facilitate genetic biocontrol with new means to effectively accomplish sex-specific selection, lethality, or sterility. For example, sex-specific splicing elements in genes in the sex determination pathway are used to produce sex-specific markers. Sex-linked recessive lethal alleles are used to differentially eliminate the transgene-marked sex chromosome from males to produce non-transgenic males. Knocking out or knocking down sex-specific isoforms of genes in the sex determination pathway is employed to confer female-specific lethality or sterility. Sex determination pathways and sex chromosomes are also targeted for gene drives that suppress pest populations by introducing extreme sex ratio biases. Here we review these and other recent advances on the genetic technologies for pest control that have benefited from knowledge of sex determination systems in Diptera.
The role of the transformer gene in sex determination and its employment in CRISPR/Cas9-based homing gene drive in the global fruit pest Drosophila suzukii
35172Dan Deng, Xueying Yi, Wen Wen, Liuqing He, Wei Peng, Insect Biochemistry and Molecular Biology, 184. 2025-09-26 14:04:36.
Sex determination of Diptera is established by the cascade genes such as transformer (tra), though the primary signals for sex determination differ among different insects. Here, we report the isolation, expression and function of tra gene in an invasive pest, Drosophila suzukii, and study the potential use of the D. suzukii tra (Dstra) gene in CRISPR/Cas9-based homing gene drive for genetic-based pest management. The Dstra gene is highly conserved in structure and has a sex-specific transcript. To test the function of this gene in sex determination, Dstra dsRNA was injected into embryos. Almost all XX embryos developed into masculinized phenotypic male adults with intersex morphology. Abnormal ovaries were revealed in XX pseudomales upon dissection. Based on the necessary role of Dstra for female development, we developed and evaluated a homing gene drive that targets Dstra in D. suzukii. The drive component consisting of multiplex Dstra single guide RNAs and Cas9 with Dsvasa promoter was introduced into the Dstra locus. Abnormal development of both the external genitalia and gonads was observed in G0 and G1 chromosomal female adults that expressed the male-specific doublesex (dsx) transcript. Interestingly, knocking out Dstra led to significantly reduced fertility in adults of corresponding sex and moderate transmission rates of the DsRed gene (63.54 %) were observed. Our results not only confirm the conserved function of the Dstra gene in sex determination, but also highlight the potential of sex conversion-based suppression gene-drive strategy targeting the Dstra gene in controlling of D. suzukii populations.
Rapid protamine evolution suppresses meiotic drive in Drosophila
35159Ching-Ho Chang, Aida Flor de la Cruz, Isabel Mejia Natividad, Alex Noyola, Harmit S. Malik, bioRxiv, 2025-09-22 10:55:08.
Many animal species replace histones with protamines during spermatogenesis. Despite their importance for sperm function, protamines rapidly evolve in many species; the biological causes behind their rapid evolution remain unknown. Here, using in vivo gene replacement, we investigated the causes and consequences underlying the rapid evolution of protamine Mst77F, which is essential for male fertility in D. melanogaster. Mst77F ortholog replacements led to defects in DNA compaction of X-chromosome-bearing sperm compared to Y-chromosome-bearing sperm during spermatogenesis, resulting in fewer X-bearing mature sperm and male-biased progeny. Unlike D. melanogaster, Mst77F is not essential for male fertility in D. yakuba but is still required to suppress sex-ratio distortion. Our results suggest that relentless pressure to suppress sex chromosomal meiotic drive drives the rapid evolution of protamines.
Single-cell consequences of X-linked meiotic drive in stalk-eyed flies
35155Price PD, Parkus SM, Lloyd VJ, Alston BT, Bradshaw SL, Bates S, et al., PLoS Genet, 21. 2025-09-22 10:33:47.
Meiotic drivers, a class of selfish gene, are frequently located on sex chromosomes and have dramatic impacts on gamete development. However, our understanding of their molecular consequences for gamete production and sex chromosome regulation has focused on a handful of model organisms. In this study, we use single-cell RNA-sequencing approaches to produce a single-cell atlas of the testis of the stalk-eyed fly, Teleopsis dalmanni. This species harbours an X-linked meiotic driver where drive males produce more than 90% female offspring. First, we generate a comprehensive profile of the cellular and transcriptional landscape of spermatogenesis. We show limited evidence for meiotic sex chromosome inactivation and unique patterns of dosage compensation across spermatogenesis, relative to both other dipterans and insects in general. Finally, by comparing single-cell expression data between standard and drive males, we show that although there are significant differences in genome regulation, broad expression dynamics in the testis are conserved in the presence of meiotic drive. Notably, we highlight key genes with perturbed expression as a potential consequence of the disruption of spermatogenesis by the X-linked meiotic driver.
Reprogramming Sex for Vector Control: Maleness-Associated Transgenes in Aedes albopictus
35151Doron Shalom Yishai Zaada, Philippos Aris Papathanos, Eric Marois, Current Opinion in Insect Science, 2025-09-22 10:21:15.
Among other challenges, the world currently faces the expansion of pest insects such as the tiger mosquito Aedes albopictus, a growing threat to public health due to the pathogens it can transmit. Current control approaches based on insecticides or elimination of mosquito larval breeding sites are insufficient to suppress this highly invasive species. The discovery of Nix, a gene necessary and sufficient to determine the male sex in this mosquito, opens new prospects for genetic control strategies, in particular those based on transgenes that convert females into males, or that reduce female fitness. Such forms of genetic control could be effective on larger spatial and time scales compared to classical control approaches. This overview of current and emerging genetic control strategies targeting Aedes mosquitoes emphasizes the unique characteristics of Ae. albopictus, that make it particularly amenable to masculinization-based genetic control.
After ‘humiliating’ raid, Burkina Faso halts ‘gene drive’ project to fight malaria
35111Kai Kupferschmidt, Science, 2025-09-03 09:35:57.
On 11 August, the international nonprofit Target Malaria celebrated a milestone: In the village of Souroukoudingan, Burkina Faso, its researchers released about 16,000 male mosquitoes genetically modified to produce almost exclusively male offspring. The release, the first of its kind in Africa, was part of a project supported by the Gates Foundation that aims to rid the world of malaria using a so-called gene drive, a controversial technique to help desirable genes spread through a population fast. But a week later, that dream suffered a major setback. On 18 August, judicial police showed up at the Research Institute in Health Sciences (IRSS) in Bobo-Dioulasso, a key partner in Target Malaria, to stage what scientists described as a “brutal, humiliating” raid. According to minutes of a 26 August meeting between researchers and the country’s science minister, IRSS scientists were “treated like criminals, with their offices and laboratories sealed and marked as crime scenes.” The minutes noted that “everyone was searched, including their vehicles, on the grounds that researchers might be carrying mosquitoes in their pockets.” Four days later, the government suspended all of Target Malaria’s activities in Burkina Faso indefinitely. IRSS scientists killed the mosquitoes still living in their insectary, and the government sent a team to spray insecticides in Souroukoudingan to kill the mosquitoes released there.
Autosomally-encoded segregation distortion of sex chromosomes
35096Greenberg Naomi L., Patten Manus M. and Schenkel Martijn A., Proc. R. Soc. B., 292. 2025-09-01 19:48:42.
Some selfish genetic elements drive at meiosis to achieve transmission distortion, breaking the rules of Mendelian segregation to enhance their own evolutionary success. It has been shown that enhancers of drive must act in cis in order to gain the selfish benefit of drive and that suppressors of drive will be selected at unlinked loci. Here, we model the evolution of an autosomal trans-acting gene (Distorter) that causes the Y chromosome (or even 0 chromosome) to drive without driving itself, a phenomenon we call ‘remote-control meiotic drive’. We show that such a gene may spread in the population when linked to a second locus, Assister, whose alleles are transmitted at different frequencies through sperm as compared to eggs, for which we consider various scenarios, such as sexually antagonistic selection or sex-limited drive. Depending on the mechanistic details of sex-chromosome drive, Distorter’s spread can additionally facilitate transitions between XY and X0 sex determination. Our results provide a proof of principle that stretches the current understanding of segregation modifier and sex allocation theory. Moreover, we identify alternative evolutionary trajectories that could also lead to remote control drive and discuss its potential applications in developing synthetic sex-ratio-distorting elements for use in pest management, for example.
Novel stressors and trait variation determine X-linked meiotic drive frequency
35021Fisher Adam M., White Nicola, Bonsall Michael B., Price Tom AR. and Knell Robert J., Proc. R. Soc. B., 292. 2025-08-13 16:09:01.
Sex ratio meiotic drive alleles bias their transmission by impairing the viability of non-drive gametes, leading to skewed population sex ratios. Despite theoretical predictions that drive alleles should reach fixation causing population extinction, meiotic drive persists at intermediate frequencies in wild populations, though the reasons for this are unclear. Here, we investigate how novel environmental stress and genotype-specific fitness costs contribute to drive frequency. Using a suppression-free X-linked meiotic drive system in Drosophila pseudoobscura, we exposed flies to varying doses of the pesticide permethrin and measured mortality and fecundity across genotypes. We found that drive-bearing males (SR) and drive-homozygous females (SRSR) exhibited heightened mortality, both in the presence and absence of pesticide, while heterozygous (SRST) females exhibited superior fecundity. Using a mathematical model parametrized with our empirical findings, we explored the long-term population dynamics of meiotic drive under different conditions. Our model predicts that drive frequency has a concave relationship with pesticide dose and is strongly modulated by genotype-specific female fecundity. These results suggest that novel environmental stressors and drive-induced fitness effects play key roles in determining meiotic drive frequencies. Our findings improve our understanding of drive frequencies in the wild and have direct implications for drive-based pest control.
CRISPR Mosquitoes That Can’t Bite
35031Science Techniz, 2025-08-09 19:49:44.
Scientists have used CRISPR gene editing to alter female mosquitoes so that their proboscis — the needle-like mouthpart used to pierce skin — develops like a male’s. The consequence is simple and profound: modified females can no longer pierce skin and therefore cannot take a blood meal or transmit human diseases like malaria and dengue. Researchers identified a gene involved in the developmental pathway that produces the female proboscis morphology. Using CRISPR-based edits, they altered that gene’s function so that genetically female mosquitoes develop a male-like mouthpart. Because males naturally do not bite (they feed on nectar), the modification removes the biting behavior without fundamentally disrupting other survival traits in lab tests. It’s important to stress that this is a high-level description intended to explain the concept, not a protocol or “how-to.” The work is complex, tightly regulated, and performed under strict laboratory and ethical oversight.
Biased tertiary sex ratios enhance the efficacy of sex-ratio distorting genetic techniques to control invasive species
34843Michael L. Jones, Ronald E. Thresher, Nicholas J. Bax, Journal of Theoretical Biology, 2025-05-12 20:32:40.
Genetic biocontrol strategies are increasingly being developed and tested for reducing the effects of invasive species, and are highly likely to be an important tool of integrated pest management in the future. Included among such strategies are those that distort the sex ratio of the target species. Models used to forecast the efficacy of such strategies generally assume, implicitly, that the tertiary sex ratio of the target population is 50:50. We present evidence that this assumption is important, and that if the tertiary sex ratio is biased towards females, a sex-distorting construct introduced into the population that produces phenotypic males will become fixed at a level determined by the magnitude of the bias, even after further introductions cease. We show, first using a simple logistic population model, and second using a realistic simulation of an important aquatic invasive species – the sea lamprey Petromyzon marinus – how this effect can greatly increase the effectiveness of a sex-distorting construct at population suppression, but also increase the risk of such strategies due to reduced reversibility. We also present evidence that biased tertiary sex ratios might be present in many invasive species, particularly when their population sizes are low relative to environmental carrying capacity.
Differential elimination of marked sex chromosomes enables production of nontransgenic male mosquitoes in a single strain
34839A. Compton, A. Sharma, M. Hempel, A. Aryan, J.K. Biedler,M.B. Potters, K. Chandrasegaran, C. Vinauger, & Z. Tu, Proceedings of the National Academy of Sciences, 122. 2025-05-12 20:01:30.
Diverse genetic strategies are being pursued to control mosquito-borne infectious diseases. These strategies often rely on the release of nonbiting males to either reduce the target mosquito population or render them resistant to pathogens. Male-only releases are important as any contaminating females can bite and potentially transmit pathogens. Despite significant efforts, it remains a major bottleneck to reliably and efficiently separate males from females, especially when nontransgenic males are preferred. In the yellow fever mosquito Aedes aegypti, sex is determined by a pair of homomorphic sex chromosomes, with the dominant male-determining locus (the M locus) and its counterpart (the m locus) embedded in an M-bearing and an m-bearing chromosome 1, respectively. We utilized both naturally occurring and engineered sex-linked recessive lethal alleles (RLAs) to create sex separation strains for Ae. aegypti on the basis of differential elimination of marked sex chromosomes (DeMark). DeMark strains are self-sustaining and produce nontransgenic males that are readily separated from individuals carrying RLA- and transgene-marked m chromosomes. For example, the marked m chromosome in the heterozygous mother in some strains was only inherited by her female progeny due to RLA-mediated incompatibility with the M-bearing chromosome in the father, producing nontransgenic males and transgenic females, generation after generation. We further explore strategies to conditionally eliminate females that contain marked sex chromosomes. We also discuss DeMark designs that are applicable for efficient sex separation in organisms with well-differentiated X and Y chromosomes, such as the Anopheles mosquitoes.
Hordes of genetically modified insects set to be released in Australia: ‘They can smell you’
34740Michael Dahlstrom, Yahoo News, 2025-04-03 17:47:00.
Dengue fever is at record levels around the globe, with this trend now beginning to be reflected in Australia as the mosquito species that carries the virus spreads. It means a simple bite could soon trigger symptoms worse than an annoying itch, with victims often experiencing pain behind the eyes, headaches, muscle aches, and nausea for over a week. Surprisingly, elsewhere in the world, one solution to combatting the spread of dengue fever is breeding more of the mosquitoes in large factories. And that’s what UK-based Oxitec is now planning to do in Australia as it partners with the country’s national science agency, the CSIRO. The company operates the world’s largest mosquito breeding factory, which is located in Brazil. Inside are boxes containing thousands of “friendly” mosquitoes that are genetically engineered so only non-biting males survive. After they’re released by local governments, they breed with wild females, and because their offspring will also be majority male, the overall population can rapidly be reduced by over 95 per cent in a few breeding cycles. Australian governments could be purchasing and releasing Oxitic’s strain of “friendly” mosquitoes in the next one to two years, if the plan receives regulatory approval.
Challenges in developing a split drive targeting dsx for the genetic control of the invasive malaria vector Anopheles stephensi
34659Larrosa-Godall, M., Ang, J.X.D., Leftwich, P.T. et al., Parasites & Vectors, 18. 2025-03-25 09:18:22.
Anopheles stephensi is a competent malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012, it has invaded several countries of eastern Africa, creating an emerging risk of urban transmission. Urgent efforts are required to develop novel and more efficient strategies for targeted vector control. CRISPR/Cas9-based homing gene drives have been proposed as attractive alternative strategies. Gene drives have the potential to spread a desired trait through a population at higher rates than via normal Mendelian inheritance, even in the presence of a fitness cost. Several target genes have been suggested and tested in different mosquito vector species such as Anopheles gambiae and Aedes aegypti. Several promising suppression drives have been developed in An. gambiae that target the sex determination gene doublesex (dsx). In this study, a geographically confineable gene drive system targeting dsx was developed (dsxgRNA). Here, a transgenic line which expresses Cas9 under the control of the endogenous zpg promoter was generated. Separately a transgenic line which expresses a gRNA targeting the female specific exon of dsx was inserted into that same target site. The reproductive fitness of males and females heterozygous and homozygous for this element was determined. A series of experimental crosses was performed to combine the two elements and assess the homing rate of the dsx element in a split drive system. The drive was able to home in a super-Mendelian rate comparable to those obtained by an autonomous drive in this species. Although inheritance rates as high as 99.8% were observed, potentially providing very potent gene drive, dominant effects on male and female fertility were observed, which would be sufficient to hinder spread of such a drive. Molecular analysis indicated that the gRNA expressing insertion disrupted normal splicing of dsx. These results should be considered when proposing the viability of dsx as a target gene for a population suppression gene drives in Anopheles stephensi. Although high homing rates were observed, the fitness defects found in both males and females carrying the transgene would likely prohibit this drive from functioning in the field.
Small RNA-mediated suppression of sex chromosome meiotic conflicts during Drosophila male gametogenesis
34613Vedanayagam, J., Biochemical Society Transactions, 53:281-291. 2025-02-06 11:14:24.
Meiosis is an evolutionarily conserved process in eukaryotes that ensures equal segregation of alleles and chromosomes during reproduction. Although parity in allelic transmission is the norm, selfish genes such as meiotic drivers can violate Mendel’s first law of segregation. Sex chromosome drive is a form of meiotic drive that leads to unequal segregation of sex chromosomes, resulting in sex-ratio distortion and/or sterility in the offspring. Adverse fitness effects due to sex chromosome drive trigger the evolution of suppressors to restore Mendelian segregation. However, the molecular mechanisms by which suppressors emerge and counteract meiotic drive genes remain unclear. Recent studies from Drosophila have shed light on the critical roles of small RNA-mediated post-transcriptional silencing in mitigating sex chromosome meiotic conflicts. This review highlights the recruitment of two distinct small RNA pathways to combat intragenomic conflicts during male gametogenesis and seeks to reveal the impact of molecular arms races between meiotic drivers and their suppressors in shaping genome and sex chromosome evolution.
Generating sterile Anopheles mosquitoes to combat malaria transmission
34492Xu, X. and Champer, J., Research Communities by Springer Nature, 2025-02-04 17:49:08.
Malaria remains a deadly disease, claiming hundreds of thousands of lives worldwide every year. The primary vectors of malaria are Anopheles mosquitoes, including Anopheles gambiae and Anopheles stephensi. Controlling mosquito populations is crucial for stopping malaria transmission. Gene drive technology represents a promising alternative to traditional chemical-based control methods, offering a species-specific and eco-friendly approach. However, key challenges in developing gene drives include resistance formation due to end-joining repair after Cas9/gRNA cleavage and the fitness costs associated with drive heterozygotes. One of the most successful gene drive designs to date targets the doublesex (dsx) gene in Anopheles gambiae, as reported by Kyrou et al. (2018). The dsx gene plays a crucial role in sex differentiation, with distinct isoforms expressed in males and females. Disrupting the female-specific isoform results in female sterility. Ideally, only homozygous females exhibit sterility due to a male-like intersex phenotype, while male homozygous and heterozygous mosquitoes of both sexes remain fertile. This makes it a suitable target for a suppression gene drive aimed at reducing the number of fertile females and ultimately eliminating the population.
Selfish Genetic Elements and Meiotic Drive in Drosophila
34367Nature Research Intelligence, 2025-01-28 14:04:45.
Selfish genetic elements are segments of DNA that can enhance their own transmission to the next generation, often at a cost to the organism's overall fitness. In Drosophila, or fruit flies, these elements can lead to a phenomenon known as meiotic drive, where certain alleles are preferentially passed on during reproduction, violating Mendel's law of equal segregation. Recent research has focused on understanding the mechanisms behind these selfish elements, their evolutionary implications, and how they can affect the fitness and reproductive success of their hosts.
Meiotic Drive and Speciation
34057Jeremy B. Searle and Fernando Pardo-Manuel de Villena, Annual Review of Genetics, 58:341-363. 2024-12-16 15:22:27.
Meiotic drive is the biased transmission of alleles from heterozygotes, contrary to Mendel's laws, and reflects intragenomic conflict rather than organism-level Darwinian selection. Theory has been developed as to how centromeric properties can promote female meiotic drive and how conflict between the X and Y chromosomes in males can promote male meiotic drive. There are empirical data that fit both the centromere drive and sex chromosome drive models. Sex chromosome drive may have relevance to speciation through the buildup of Dobzhansky-Muller incompatibilities involving drive and suppressor systems, studied particularly in Drosophila. Centromere drive may promote fixation of chromosomal rearrangements involving the centromere, and those fixed rearrangements may contribute to reproductive isolation, studied particularly in the house mouse. Genome-wide tests suggest that meiotic drive promotes allele fixation with regularity, and those studying the genomics of speciation need to be aware of the potential impact of such fixations on reproductive isolation. New species can originate in many different ways (including multiple factors acting together), and a substantial body of work on meiotic drive point to it being one of the processes involved.
Autosomal suppression of sex-ratio meiotic drive influences the dynamics of X and Y chromosome coevolution
31322Anjali Gupta, Robert L Unckless, Journal of Heredity, 2024-09-03 15:54:00.
Sex-ratio meiotic drivers are selfish genes or gene complexes that bias the transmission of sex chromosomes resulting in skewed sex ratios. Existing theoretical models have suggested the maintenance of a four-chromosome equilibrium (with driving and standard X and suppressing and susceptible Y) in a cyclic dynamic, studies of natural populations have failed to capture this pattern. Although there are several plausible explanations for this lack of cycling, interference from autosomal suppressors has not been studied using a theoretical population genetic framework even though autosomal suppressors and Y-linked suppressors coexist in natural populations of some species. In this study, we use a simulation-based approach to investigate the influence of autosomal suppressors on the cycling of sex chromosomes. Our findings demonstrate that the presence of an autosomal suppressor can hinder the invasion of a Y-linked suppressor under some parameter space, thereby impeding the cyclic dynamics, or even the invasion of Y-linked suppression. Even when a Y-linked suppressor invades, the presence of an autosomal suppressor can prevent cycling. Our study demonstrates the potential role of autosomal suppressors in preventing sex chromosome cycling and provides insights into the conditions and consequences of maintaining both Y-linked and autosomal suppressors.
Transformation of meiotic drive into hybrid sterility in Drosophila
30352Jackson Bladen, Hyuck-Jin Nam, Nitin Phadnis, bioRxiv, 2024-05-21 19:05:25.
Hybrid male sterility is one of the fastest evolving intrinsic reproductive barriers between recently isolated populations. A leading explanation for the evolution of hybrid male sterility involves genomic conflicts with meiotic drivers in the male germline. There are, however, few examples directly linking meiotic drive to hybrid sterility. Here, we report that the Sex-Ratio chromosome of Drosophila pseudoobscura, which causes X-chromosome drive within the USA subspecies, causes near complete male sterility when moved into the genetic background of the Bogota subspecies. In addition, we show that this new form of sterility is genetically distinct from the sterility of F1 hybrid males in crosses between USA males and Bogota females. Our observations provide a tractable study system where non-cryptic drive within species is transformed into strong hybrid sterility between very young subspecies.
The haplolethal gene wupA of Drosophila exhibits potential as a target for an X-poisoning gene drive
28845Clancy D. Lawler, Ana Karla Parra Nuñez, Natalia Hernandes, Soumitra Bhide, Isabelle Lohrey, Simon Baxter, Charles Robin, bioRxiv, 2024-01-28 12:54:44.
A synthetic gene drive that targets haplolethal genes on the X-chromosome can skew the sex ratio towards males. Like an ‘X-shredder’ it does not involve ‘homing’ and that has advantages including the reduction of gene drive resistance allele formation. We examine this ‘X-poisoning’ strategy by targeting four of the 11 known X-linked haplolethal/haplosterile genes of Drosophila melanogaster with CRISPR/Cas9. We find that targeting the wupA gene during spermatogenesis skews the sex ratio so fewer than 14% of progeny are daughters. That is unless we cross the mutagenic males to X^XY female flies that bear attached-X chromosomes, which reverses the inheritance of the poisoned X chromosome so that sons inherit it from their father; in which case only 2% of the progeny are sons. These sex ratio biases suggests that most of the CRISPR/Cas9 mutants we induced in the wupA gene are haplolethal but some are recessive lethal. The males generating wupA mutants do not suffer from reduced fertility rather the haplolethal mutants arrest development in the late stages of embryogenesis well after fertilized eggs have been laid. This provides a distinct advantage over genetic manipulation strategies involving sterility which can be countered by the remating of females. We also find that wupA mutants that destroy the nuclear localization signal of shorter isoforms are not haplolethal as long as the open reading frame remains intact. Like D. melanogaster wupA orthologs of D. suzukii and Anopheles mosquitos are found on X chromosomes making wupA a viable X-poisoning target in multiple species.
Gene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata
28802Meccariello, A., Hou, S., Davydova, S. et al., Nature Communications, 15:372. 2024-01-15 17:13:20.
Homing-based gene drives are recently proposed interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here we characterise a first set of gene drives in a tephritid agricultural pest species, the Mediterranean fruit fly Ceratitis capitata (medfly). Our results show that the medfly is highly amenable to homing-based gene drive strategies. By targeting the medfly transformer gene, we also demonstrate how CRISPR-Cas9 gene drive can be coupled to sex conversion, whereby genetic females are transformed into fertile and harmless XX males. Given this unique malleability of sex determination, we modelled gene drive interventions that couple sex conversion and female sterility and found that such approaches could be effective and tolerant of resistant allele selection in the target population. Our results open the door for developing gene drive strains for the population suppression of the medfly and related tephritid pests by co-targeting female reproduction and shifting the reproductive sex ratio towards males. They demonstrate the untapped potential for gene drives to tackle agricultural pests in an environmentally friendly and economical way.
Male-killing virus leads to more female moths
28365Anonymous, Nature, 2023-11-07 09:51:08.
Keisuke Nagamine at Minami Kyushu University in Miyazaki, Japan, and his colleagues have identified another virus that kills male embryos of the tobacco caterpillar, Spodoptera litura. Female moths infected with the virus produced an equal number of male and female embryos, but almost no male embryos survived. The virus doesn’t share male-killing genes with other known male-killing viruses or bacteria, suggesting that these mechanisms evolved independently.
Male-killing virus in a noctuid moth Spodoptera litura
28367K. Nagamine, Y. Kanno, K. Sahara, T. Fujimoto, A. Yoshido, Y. Ishikawa, M. Terao, D. Kageyama and Y. Shintani, Proceedings of the National Academy of Sciences, 120:e2312124120. 2023-11-06 09:56:12.
A female-biased sex ratio is considered advantageous for the cytoplasmic elements that inhabit sexually reproducing organisms. There are numerous examples of bacterial symbionts in the arthropod cytoplasm that bias the host sex ratio toward females through various means, including feminization and male killing. Recently, maternally inherited RNA viruses belonging to the family Partitiviridae were found to cause male killing in moths and flies, but it was unknown whether male-killing viruses were restricted to Partitiviridae or could be found in other taxa. Here, we provide compelling evidence that a maternally inherited RNA virus, Spodoptera litura male-killing virus (SlMKV), selectively kills male embryos of the tobacco caterpillar Spodoptera litura, resulting in all-female broods. SlMKV injected into uninfected S. litura can also be inherited maternally and causes male killing. SlMKV has five genomic segments encoding seven open reading frames, has no homolog of known male-killing genes, and belongs to an unclassified group of arthropod-specific viruses closely related to Tolivirales. When transinfected into larvae, both male and female recipients allow SlMKV to proliferate, but only males die at the pupal stage. The viral RNA levels in embryonic and pupal male killing suggest that the mechanism of male killing involves the constitutive expression of viral products that are specifically lethal to males, rather than the male-specific expression of viral products. Our results, together with recent findings on male-killing partiti-like viruses, suggest that diverse viruses in arthropods tend to acquire male killing independently and that such viruses may be important components of intragenomic conflict in arthropods.
Quantifying Fitness Costs in Transgenic Aedes aegypti Mosquitoes
27981I. Sanchez-Vargas, A. E. Williams, L. E. Martin, I. Martin-Martin, S. Bennett, K. E. Olson and E. Calvo, Journal of Visualized Experiments, 2023-09-15 07:51:42.
Transgenic mosquitoes often display fitness costs compared to their wild-type counterparts. In this regard, fitness cost studies involve collecting life parameter data from genetically modified mosquitoes and comparing them to mosquitoes lacking transgenes from the same genetic background. This manuscript illustrates how to measure common life history traits in the mosquito Aedes aegypti, including fecundity, wing size and shape, fertility, sex ratio, viability, development times, male contribution, and adult longevity. These parameters were chosen because they reflect reproductive success, are simple to measure, and are commonly reported in the literature. The representative results quantify fitness costs associated with either a gene knock-out or a single insertion of a gene drive element. Standardizing how life parameter data are collected is important because such data may be used to compare the health of transgenic mosquitoes generated across studies or to model the transgene fixation rate in a simulated wild-type mosquito population. Although this protocol is specific for transgenic Aedes aegypti, the protocol may also be used for other mosquito species or other experimental treatment conditions, with the caveat that certain biological contexts may require special adaptations.
Female meiotic drive in plants: mechanisms and dynamics
27709F. Finseth, Current Opinion in Genetics and Development, 82:102101. 2023-08-24 09:45:29.
Female meiosis is fundamentally asymmetric, creating an arena for genetic elements to compete for inclusion in the egg to maximize their transmission. Centromeres, as mediators of chromosomal segregation, are prime candidates to evolve via ‘female meiotic drive’. According to the centromere-drive model, the asymmetry of female meiosis ignites a coevolutionary arms race between selfish centromeres and kinetochore proteins, the by-product of which is accelerated sequence divergence. Here, I describe and compare plant models that have been instrumental in uncovering the mechanistic basis of female meiotic drive (maize) and the dynamics of active selfish centromeres in nature (monkeyflowers). Then, I speculate on the mechanistic basis of drive in monkeyflowers, discuss how centromere strength influences chromosomal segregation in plants, and describe new insights into the evolution of plant centromeres.
Assessing the suitability of YY males and ZZ females as an invasive species population control method across life histories
28170R. A. Erickson, H. M. Thompson, S. A. Kageyama, G. M. Andriacchi, A. R. Cupp, R. Patiño and J. J. Amberg, Biological Invasions, 25:3737-3751. 2023-08-12 12:16:15.
Natural resource managers use tools to control invasive species. In theory, stocking YY males or ZZ females would allow managers to skew sex ratios until populations collapse. In combination with other suppression methods, such as removal, this approach could be incorporated into Integrated Pest Management plans. For example, fishery managers have stocked YY males to control isolated non-native brook trout (Salvelinus fontinalis) populations. However, life histories and demographic factors (e.g., lifespans) vary across species and could affect the feasibility of skewing sex ratios as an effective control strategy for a given population. Likewise, some species may have sex determinations that do not allow population control through sex-skewing methods. We compared five representative aquatic invasive species with global invasion ranges for potential control by skewing the sex ratio through closed population simulations: red swamp crayfish (Procambarus clarkii), zebra mussels (Dreissena polymorpha), lake trout (Salvelinus namaycush), silver carp (Hypophthalmichthys molitrix), and Nile tilapia (Oreochromis niloticus). We determined that Nile tilapia, red swamp crayfish, and zebra mussels would be the most suitable to control through skewing the sex ratio assuming appropriate sex determination exists in the species. Lake trout could be eliminated by stocking YY males but would require either long stocking periods or high stocking numbers because of the long lifespan of the species. Silver carp populations were more difficult to crash because they live longer and produce many recruits. Broadly, these patterns demonstrated that short lived species lend themselves to control by skewing the sex ratio.
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.
Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila
26903C. Weizhe, G. Jialiang, L. Yiran and C. Jackson, bioRxiv, 2023.07.17.549342. 2023-07-17 11:00:13.
Gene drive alleles, which bias their own inheritance and increase in frequency, show great promise for blocking disease transmission or directly suppressing pest populations. The most common engineered drive system is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of drive heterozygotes by homology-directed repair after CRISPR cleavage. One successful homing drive example targets a female-specific exon in doublesex in Anopheles mosquitos, suppressing the population by inducing recessive sterility in female drive homozygotes. We found that in Drosophila melanogaster, a 3-gRNA drive disrupting the doublesex female exon resulted in a masculine phenotype and dominant female sterility. Resistance alleles formed by end-joining repair were also dominant sterile. This was likely caused by expression of male-specific transcripts in females with drive and resistance alleles, disrupting sex development. Based on this construct, we proposed a new pest suppression system called Release of Insects carrying a Dominant-sterile Drive (RIDD). This entails continuously releasing drive heterozygous males, with drive and resistance alleles causing sterility in females. The drive remains at high frequency longer than currently used dominant female-lethal alleles (RIDL) due to drive conversion in males, and drive alleles also cause sterility based on resistance, both substantial advantages. With weekly releases of drive males into a cage population with overlapping generations, our RIDD system targeting dsx reached 100% prevalence within 27 weeks, progressively reducing egg production and eventually causing total population collapse. RIDD combines the merits of homing gene drive and RIDL. It is powerful but self-limiting, unlike unconfined standard homing drives, allowing for targeted population suppression.Competing Interest StatementThe authors have declared no competing interest.
26619
N. Wybouw, E. Van Reempts, J. Zarka, F. Zélé and D. Bonte, Heredity, 2023-07-13 08:18:54.
Maternally transmitted symbionts such as Wolbachia can alter sex allocation in haplodiploid arthropods. By biasing population sex ratios towards females, these changes in sex allocation may facilitate the spread of symbionts. In contrast to symbiont-induced cytoplasmic incompatibility (CI), the mechanisms that underpin sex allocation distortion remain poorly understood. Using a nuclear genotype reference panel of the haplodiploid mite Tetranychus urticae and a single Wolbachia variant that is able to simultaneously induce sex allocation distortion and CI, we unraveled the mechanistic basis of Wolbachia-mediated sex allocation distortion. Host genotype was an important determinant for the strength of sex allocation distortion. We further show that sex allocation distortion by Wolbachia in haplodiploid mites is driven by increasing egg size, hereby promoting egg fertilization. This change in reproductive physiology was also coupled to increased male and female adult size. Our results echo previous work on Cardinium symbionts, suggesting that sex allocation distortion by regulating host investment in egg size is a common strategy among symbionts that infect haplodiploids. To better understand the relevance that sex allocation distortion may have for the spread of Wolbachia in natural haplodiploid populations, we parametrized a model based on generated phenotypic data. Our simulations show that empirically derived levels of sex allocation distortion can be sufficient to remove invasion thresholds, allowing CI to drive the spread of Wolbachia independently of the initial infection frequency. Our findings help elucidate the mechanisms that underlie the widespread occurrence of symbionts in haplodiploid arthropods and the evolution of sex allocation.
The evolutionary history of Drosophila simulans Y chromosomes reveals molecular signatures of resistance to sex ratio meiotic drive
26469C. Courret, D. Ogereau, C. Gilbert, A. M. Larracuente and C. Montchamp-Moreau, Mol Biol Evol, 2023-07-04 07:54:47.
The recent evolutionary history of the Y chromosome in Drosophila simulans, a worldwide species of Afrotropical origin, is closely linked to that of X-linked meiotic drivers (Paris system). The spread of the Paris drivers in natural populations has elicited the selection of drive resistant Y chromosomes. To infer the evolutionary history of the Y chromosome in relation to the Paris drive, we sequenced 21 iso-Y lines, each carrying a Y chromosome from a different location. Among them, 13 lines carry a Y chromosome that is able to counteract the effect of the drivers. Despite their very different geographical origins, all sensitive Y's are highly similar, suggesting that they share a recent common ancestor. The resistant Y chromosomes are more divergent and segregate in four distinct clusters. The phylogeny of the Y chromosome confirms that the resistant lineage predates the emergence of Paris drive. The ancestry of the resistant lineage is further supported by the examination of Y-linked sequences in the sister species of D. simulans, D. sechellia, and D. mauritiana. We also characterized the variation in repeat content among Y chromosomes and identified multiple simple satellites associated with resistance. Altogether, the molecular polymorphism allows us to infer the demographic and evolutionary history of the Y chromosome and provides new insights on the genetic basis of resistance.
Meiotic drive of noncentromeric loci in mammalian meiosis II eggs
26477D. M. Silva and T. Akera, Curr Opin Genet Dev, 81:102082. 2023-07-03 08:21:48.
The germline produces haploid gametes through a specialized cell division called meiosis. In general, homologous chromosomes from each parent segregate randomly to the daughter cells during meiosis, providing parental alleles with an equal chance of transmission. Meiotic drivers are selfish elements who cheat this process to increase their transmission rate. In female meiosis, selfish centromeres and noncentromeric drivers cheat by preferentially segregating to the egg cell. Selfish centromeres cheat in meiosis I (MI), while noncentromeric drivers can cheat in both meiosis I and meiosis II (MII). Here, we highlight recent advances on our understanding of the molecular mechanisms underlying these genetic cheating strategies, especially focusing on mammalian systems, and discuss new models of how noncentromeric selfish drivers can cheat in MII eggs.
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.
A male-killing gene encoded by a symbiotic virus of Drosophila
24838D. Kageyama, T. Harumoto, K. Nagamine, A. Fujiwara, T. N. Sugimoto, A. Jouraku, M. Tamura, T. K. Katoh and M. Watada, Nature Communications, 14:1357. 2023-03-13 08:49:35.
In most eukaryotes, biparentally inherited nuclear genomes and maternally inherited cytoplasmic genomes have different evolutionary interests. Strongly female-biased sex ratios that are repeatedly observed in various arthropods often result from the male-specific lethality (male-killing) induced by maternally inherited symbiotic bacteria such as Spiroplasma and Wolbachia. However, despite some plausible case reports wherein viruses are raised as male-killers, it is not well understood how viruses, having much smaller genomes than bacteria, are capable of inducing male-killing. Here we show that a maternally inherited double-stranded RNA (dsRNA) virus belonging to the family Partitiviridae (designated DbMKPV1) induces male-killing in Drosophila. DbMKPV1 localizes in the cytoplasm and possesses only four genes, i.e., one gene in each of the four genomic segments (dsRNA1−dsRNA4), in contrast to ca. 1000 or more genes possessed by Spiroplasma or Wolbachia. We also show that a protein (designated PVMKp1; 330 amino acids in size), encoded by a gene on the dsRNA4 segment, is necessary and sufficient for inducing male-killing. Our results imply that male-killing genes can be easily acquired by symbiotic viruses through reassortment and that symbiotic viruses are hidden players in arthropod evolution. We anticipate that host-manipulating genes possessed by symbiotic viruses can be utilized for controlling arthropods.
Heterogeneous distribution of sex ratio distorters in natural populations of the isopod Armadillidium vulgare
24464S. Durand, B. Lheraud, I. Giraud, N. Bech, F. Grandjean, T. Rigaud, J. Peccoud and R. Cordaux, Biology Letters, 19:20220457. 2023-01-11 08:32:10.
In the isopod Armadillidium vulgare, many females produce progenies with female-biased sex ratios, owing to two feminizing sex ratio distorters (SRD): Wolbachia endosymbionts and the f element. We investigated the distribution and population dynamics of these SRD and mitochondrial DNA variation in 16 populations from Europe and Japan. Confirming and extending results from the 1990s, we found that the SRD are present at variable frequencies in populations and that the f element is overall more frequent than Wolbachia. The two SRD never co-occur at high frequency in any population, suggesting an apparent mutual exclusion. We also detected Wolbachia or the f element in some males, which probably reflects insufficient titer to induce feminization or presence of masculinizing alleles. Our results are consistent with a single integration event of a Wolbachia genome in the A. vulgare genome at the origin of the f element, which contradicts an earlier hypothesis of frequent losses and gains. We identified strong linkage between Wolbachia strains and mitochondrial haplotypes, but no association between the f element and mitochondrial background. Our results open new perspectives on SRD evolutionary dynamics in A. vulgare, the evolution of genetic conflicts and their impact on the variability of sex determination systems.
Gene drive designs for efficient and localisable population suppression using Y-linked editors
24339R. Geci, K. Willis and A. Burt, PLOS Genetics, 18:e1010550. 2022-12-27 08:45:03.
Author summary Some pest populations can be successfully controlled by the inundative release of sterile males, but this approach is not practicable when the target population is large or the species difficult to rear. Computer modelling has previously demonstrated that releasing males with a genomic editor on their Y chromosome that kills or sterilises female descendants could be much more efficient, particularly if combined with a sex ratio distorter. Here we extend this work to show that Y-linked editors can also be used in even more efficient gene drive designs that would spread over successive generations beyond the region of release. Such spread could nonetheless be controlled by exploiting relatively small pre-existing differences in gene frequency between populations to restrict the spread and impact of the constructs, if desired. The proposed design does not require high rates of recombinational repair of DNA breaks or expression off the Y chromosome during meiosis, potentially expanding the range of species in which such low release rate control is possible. Y-linked editors may therefore form the basis of a highly flexible set of genetic strategies for population control.
A natural gene drive could steer invasive rodents on islands to extinction
24129B. Brookshire, ScienceNews, 2022-12-05 09:12:58.
In the battle against the invasive house mouse on islands, scientists are using the rodent’s own genes against it. With the right tweaks, introducing a few hundred genetically altered mice could drive an island’s invasive mouse population to extinction in about 25 years, researchers report in the Nov. 15 Proceedings of the National Academy of Sciences. The trick is adding the changes to a section of mouse DNA that gets inherited far more often than it should. Scientists have been creating similar extra-inheritable genes — called gene drives — in the lab. The chunks are designed to get passed on to most or all of an animal’s offspring instead of the usual half, and make those offspring infertile in the bargain. Scientists have used gene drives to reduce populations of mosquitoes and fruit flies (SN: 12/17/18). But mammals are a different story. Scientists have previously synthesized a gene drive that gets passed on in mice about 80 percent of the time (SN: 1/23/19). But the drive isn’t strong enough to stop a population quickly. Luckily, nature has it handled. A haplotype is a naturally occurring group of genes that gets passed on as a unit during replication. The genome of the house mouse (Mus musculus) has a particular haplotype, called the t haplotype, that gets passed on to offspring more than 95 percent of the time, instead of the typical 50 percent.
Deregulation of Y-linked protamine-like genes in sex chromosome-biased spermatid demise
24124J. I. Park, G. W. Bell and Y. M. Yamashita, bioRxiv, 2022-12-05 08:57:46.
Meiotic drive is a phenomenon wherein a genetic element achieves a higher rate of transmission than dictated by Mendelian segregation (1-3). One proposed mechanism for meiotic drivers to achieve biased transmission is by sabotaging essential processes of gametogenesis (e.g. spermatogenesis), leading to demise of gametes that contain their opponents (1). Studies in D. simulans have recently found that a set of meiotic driver genes contain a sequence homologous to protamines (4, 5), critical proteins that package sperm chromatin (6-8). However, the underlying mechanisms of drive and the relevance of protamine-like sequences in meiotic drive remain unknown. While studying the function of Modulo, the homolog of Nucleolin in Drosophila melanogaster (9, 10), we unexpectedly discovered Y-linked protamine genes function as a meiotic driver: we found that modulo mutant's known sterility is caused by deregulation of the autosomal protamine-like gene (Mst77F) and its Y chromosome-linked homolog (Mst77Y). Modulo regulates these genes at the step of polyadenylation of the transcripts. We show that Mst77Y likely acts as a dominant-negative form of Mst77F, interfering with the process of histone-to-protamine transition, leading to nuclear decompaction. Overexpression of Mst77Y in a wild-type background is sufficient to cause nuclear decompaction and results in the biased demise of X chromosome-bearing sperm. We propose that dominant-negative protamine variants may be a common strategy found in male meiotic drive and may explain known rapid divergence of protamine genes.Competing Interest StatementThe authors have declared no competing interest.
Meiotic drive adaptive testes enlargement during early development in the stalk-eyed fly
24087S. L. Bradshaw, L. Meade, J. Tarlton-Weatherall and A. Pomiankowski, Biology Letters, 18:20220352. 2022-11-30 09:02:09.
The sex ratio (SR) X-linked meiotic drive system in stalk-eyed flies destroys Y-bearing sperm. Unlike other SR systems, drive males do not suffer fertility loss. They have greatly enlarged testes which compensate for gamete killing. We predicted that enlarged testes arise from extended development with resources re-allocated from the accessory glands, as these tend to be smaller in drive males. To test this, we tracked the growth of the testes and accessory glands of wild-type and drive males over 5-6 weeks post-eclosion before males attained sexual maturity. Neither of the original predictions is supported by these data. Instead, we found that the drive male testes were enlarged at eclosion, reflecting a greater allocation of resources to the testes during pupation. Testes grow at a higher rate during early adult development in drive males, but there was no evidence that this retards the growth of the accessory glands. Further experiments are proposed to investigate whether smaller accessory glands only arise in drive males post-copulation or when flies are subjected to nutritional stress. Our experimental findings support the idea that enlarged testes in drive males arise as an adaptive allocation of resources to traits that enhance male reproductive success.
Introgression of a synthetic sex ratio distortion transgene into different genetic backgrounds of Anopheles coluzzii
23760P. Pollegioni, T. Persampieri, R. L. Minuz, A. Bucci, A. Trusso, S. Di Martino, C. Leo, M. Bruttini, M. Ciolfi, A. M. Waldvogel, F. Tripet, A. Simoni, A. Crisanti and R. Müller, Insect Molecular Biology, 2022-10-17 06:14:10.
The development of genetically modified mosquitoes (GMM) and their subsequent field release offers innovative approaches for vector control of malaria. A non-gene drive self-limiting male-bias Ag(PMB)1 strain has been developed in a 47-year-old laboratory G3 strain of Anopheles gambiae s.l. When Ag(PMB)1 males are crossed to wild-type females, expression of the endonuclease I-PpoI during spermatogenesis causes the meiotic cleavage of the X chromosome in sperm cells, leading to fertile offspring with a 95% male bias. However, WHO states that the functionality of the transgene could differ when inserted in different genetic backgrounds of An. coluzzii which is currently a predominant species in several West-African countries and thus a likely recipient for a potential release of self-limiting GMMs. In this study, we introgressed the transgene from the donor Ag(PMB)1 by six serial backcrosses into two recipient colonies of An. coluzzii that had been isolated in Mali and Burkina Faso. Scans of informative SNP markers and whole-genome sequencing analysis revealed a nearly complete introgression of chromosome 3 and X, but a remarkable genomic divergence in a large region of the chromosome 2 between the later backcrossed (BC6) transgenic offspring and the recipient paternal strains. These findings suggested to extend the backcrossing breeding strategy beyond BC6 generation and increase the introgression efficiency of critical regions that have ecological and epidemiological implications through the targeted selection of specific markers. Disregarding of differential introgression efficiency, we concluded that the phenotype of the sex ratio distorter is stabile in the BC6 introgressed An. coluzzii strains. This article is protected by copyright. All rights reserved.
Mitotic exchange in female germline stem cells is the major source of Sex Ratio chromosome recombination in Drosophila pseudoobscura
23719S. Koury, G3 Genes|Genomes|Genetics, 2022-10-04 06:48:20.
Sex Ratio chromosomes in Drosophila pseudoobscura are selfish X chromosome variants associated with three non-overlapping inversions. In the male germline, Sex Ratio chromosomes distort segregation of X and Y chromosomes (99:1), thereby skewing progeny sex ratio. In the female germline, segregation of Sex Ratio chromosomes is mendelian (50:50), but non-overlapping inversions strongly suppress recombination establishing a 26 Megabase haplotype (constituting ∼20% of the haploid genome). Rare crossover events located between non-overlapping inversions can disrupt this haplotype, and recombinants have sometimes been found in natural populations. We recently reported on the first lab-generated Sex Ratio recombinants occurring at a rate of 0.0012 crossovers per female meiosis. An improved experimental design presented here reveals these recombination events were at least 4-fold more frequent than previously estimated. Furthermore, recombination events were strongly clustered, indicating the majority arose from mitotic exchange in female germline stem cells and not from meiotic crossing-over in primary oocytes. Finally, asymmetric recovery of complementary recombinants was consistent with unequal exchange causing the recombination-induced viability defects. Incorporating these experimental results into population models for Sex Ratio chromosome evolution provided a substantially better fit to natural population frequencies and allowed maintenance of the highly differentiated 26 Megabase Sex Ratio haplotype without invoking strong epistatic selection. This study provides the first estimate of spontaneous mitotic exchange for naturally-occurring chromosomes in Drosophila female germline stem cells, reveals a much higher Sex Ratio chromosome recombination rate, and develops a mathematical model that accurately predicts the rarity of recombinant Sex Ratio chromosomes in natural populations.
Distribution of sex ratio distorters in natural populations of the isopod Armadillidium vulgare
236442022-09-30 08:15:09.
Hoisted with his own petard: How sex-ratio meiotic drive in Drosophila affinis creates resistance alleles that limit its spread
23471W. J. Ma, E. M. Knoles, K. B. Patch, M. M. Shoaib and R. L. Unckless, J Evol Biol, 2022-08-23 07:13:52.
Meiotic drivers are selfish genetic elements that tinker with gametogenesis to bias their own transmission into the next generation of offspring. Such tinkering can have significant consequences on gametogenesis and end up hampering the spread of the driver. In Drosophila affinis, sex-ratio meiotic drive is caused by an X-linked complex that, when in males with a susceptible Y chromosome, results in broods that are typically more than 95% female. Interestingly, D. affinis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons-effectively reversing the sex-ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 750X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex-ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex-ratio X chromosome, and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex-chromosome turnover indirectly.
Meiotic drive in house mice: mechanisms, consequences, and insights for human biology
23233U. P. Arora and B. L. Dumont, Chromosome Research, 2022-07-13 06:38:49.
Meiotic drive occurs when one allele at a heterozygous site cheats its way into a disproportionate share of functional gametes, violating Mendel's law of equal segregation. This genetic conflict typically imposes a fitness cost to individuals, often by disrupting the process of gametogenesis. The evolutionary impact of meiotic drive is substantial, and the phenomenon has been associated with infertility and reproductive isolation in a wide range of organisms. However, cases of meiotic drive in humans remain elusive, a finding that likely reflects the inherent challenges of detecting drive in our species rather than unique features of human genome biology. Here, we make the case that house mice (Mus musculus) present a powerful model system to investigate the mechanisms and consequences of meiotic drive and facilitate translational inferences about the scope and potential mechanisms of drive in humans. We first detail how different house mouse resources have been harnessed to identify cases of meiotic drive and the underlying mechanisms utilized to override Mendel's rules of inheritance. We then summarize the current state of knowledge of meiotic drive in the mouse genome. We profile known mechanisms leading to transmission bias at several established drive elements. We discuss how a detailed understanding of meiotic drive in mice can steer the search for drive elements in our own species. Lastly, we conclude with a prospective look into how new technologies and molecular tools can help resolve lingering mysteries about the prevalence and mechanisms of selfish DNA transmission in mammals.
Partial masculinization of Aedes aegypti females by conditional expression of Nix
23113B. B. Kojin, E. Jakes, J. K. Biedler, Z. Tu and Z. N. Adelman, PLOS Neglected Tropical Diseases, 16:e0010598. 2022-07-01 08:17:41.
Here, we report on the conditional expression of Nixin transgenic A. aegypti under the control of the tetracycline-dependent (Tet-off) system, with the goal of establishing repressible sex distortion. A masculinization phenotype was observed in three of the seven transgenic lines with females exhibiting male-like long maxillary palps and most importantly, the masculinized females were unable to blood feed. Doxycycline treatment of the transgenic lines only partially restored the normal phenotype from the masculinized transgenic lines, while RT-qPCR analysis of early embryos or adults showed no correlation between the level of masculinization and ectopic Nix expression. While the conditional expression of Nix produced intersex phenotypes, the level of expression was insufficient to program full conversion. Modifications that increase both the level of activation (no tet) and the level of repression (with tet) will be necessary, as such this study represents one step forward in the development of genetic strategies to control vector-borne diseases via sex ratio distortion.
Hoisted with his own petard: how sex-ratio meiotic drive in <em>Drosophila affinis</em> creates resistance alleles that limit its spread
23231W.-J. Ma, E. M. Knoles, K. B. Patch, M. M. Shoaib and R. L. Unckless, bioRxiv, 2022.02.14.480432. 2022-06-19 06:28:31.
Meiotic drivers are selfish genetic elements that tinker with gametogenesis to bias their own transmission into the next generation of offspring. Such tinkering can have significant consequences on gametogenesis and end up hampering the spread of the driver. In Drosophila affinis, sex-ratio meiotic drive is caused by an X-linked complex that, when in males with a susceptible Y chromosome, results in broods that are typically more than 95% female. Interestingly, D. affinis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons - effectively reversing the sex-ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 750X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex-ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex-ratio X chromosome and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex-chromosome turnover indirectly.Competing Interest StatementThe authors have declared no competing interest.
Natural and Engineered Sex Ratio Distortion in Insects
23010A. Compton and Z. Tu, Frontiers in Ecology and Evolution, 10. 2022-06-15 08:25:52.
Insects have evolved highly diverse genetic sex-determination mechanisms and a relatively balanced male to female sex ratio is generally expected. However, selection may shift the optimal sex ratio while meiotic drive and endosymbiont manipulation can result in sex ratio distortion (SRD). Recent advances in sex chromosome genomics and CRISPR/Cas9-mediated genome editing brought significant insights into the molecular regulators of sex determination in an increasing number of insects and provided new ways to engineer SRD. We review these advances and discuss both naturally occurring and engineered SRD in the context of the Anthropocene. We emphasize SRD-mediated biological control of insects to help improve One Health, sustain agriculture, and conserve endangered species.
Generation of Gene Drive Mice for Invasive Pest Population Suppression
22890M. D. Bunting, C. Pfitzner, L. Gierus, M. White, S. Piltz and P. Q. Thomas, Applications of Genome Modulation and Editing, 2022-06-14 06:00:54.
Gene drives are genetic elements that are transmitted to greater than 50% of offspring and have potential for population modification or suppression. While gene drives are known to occur naturally, the recent emergence of CRISPR-Cas9 genome-editing technology has enabled generation of synthetic gene drives in a range of organisms including mosquitos, flies, and yeast. For example, studies in Anopheles mosquitos have demonstrated >95% transmission of CRISPR-engineered gene drive constructs, providing a possible strategy for malaria control. Recently published studies have also indicated that it may be possible to develop gene drive technology in invasive rodents such as mice. Here, we discuss the prospects for gene drive development in mice, including synthetic “homing drive” and X-shredder strategies as well as modifications of the naturally occurring t haplotype. We also provide detailed protocols for generation of gene drive mice through incorporation of plasmid-based transgenes in a targeted and non-targeted manner. Importantly, these protocols can be used for generating transgenic mice for any project that requires insertion of kilobase-scale transgenes such as knock-in of fluorescent reporters, gene swaps, overexpression/ectopic expression studies, and conditional “floxed” alleles.
Male-killing-associated bacteriophage WO identified from comparisons of Wolbachia endosymbionts of Homona magnanima
22901H. Arai, H. Anbutsu, Y. Nishikawa, M. Kogawa, K. Ishii, M. Hosokawa, S.-R. Lin, M. Ueda, M. Nakai, Y. Kunimi, T. Harumoto, D. Kageyama, H. Takeyama and M. N. Inoue, bioRxiv, 2022-06-13 06:22:33.
The origin and mechanism of male-killing, an advantageous strategy employed by maternally transmitted symbionts such as Wolbachia, remain unclear. We compared genomes of four Wolbachia strains derived from Homona magnanima, a male-killing strain wHm-t (1.5 Mb), and three non-male-killing strains, wHm-a (1.1 Mb), wHm-b (1.3 Mb), and wHm-c (1.4 Mb). A wHm-t-specific 76-kbp prophage region harboured two tandemly arrayed WO-mediated killing (wmk) gene homologs (wmk-1/wmk-2 and wmk-3/wmk-4). Of these, wmk-1 or wmk-3 killed almost all Drosophila melanogaster individuals when transgenically overexpressed. Dual expression of wmk-3 and wmk-4 killed all males and rescued females. We propose a novel hypothesis wherein horizontally transmitted proto-Wolbachia with a single wmk killed both sexes, and tandem duplication of wmk allowed an evolutionary transition to a vertically transmitted symbiont, causing male-killing. Our study highlights the bacteriophage as a critical driver of the evolution of male-killing and argues for a conserved male-killing mechanism in diverse insects.Competing Interest StatementThe authors have declared no competing interest.
Combined Trojan Y Chromosome Strategy and Sterile Insect Technique to Eliminate Mosquitoes: Modelling and Analysis
23051J. Lyu, M. Gu, S. Wang and K. Cheng, Mathematical Problems in Engineering, 2022:2373350. 2022-05-27 15:09:13.
Sterile insect technique has been successfully applied in the control of agricultural pests; however, it has a limited ability to control mosquitoes. A promising alternative approach is the Trojan Y Chromosome strategy, which works by manipulating the sex ratio of a population through the introduction of YY supermales that guarantee male offspring. To take the advantages of both approaches, a combined Trojan Y chromosome strategy and sterile insect technique (TYC-SIT) strategy considering intraspecies competition is modeled. The pure TYC method is compared with the pure SIT method by cancelling one-state variable. The dynamical analysis leads to results on both local and global stabilities of this combined TYC-SIT model. Optimal control analysis is also implemented to investigate the optimal mechanisms for extinction of mosquitoes. In particular, the numerical results affirm that the combined TYC-SIT enables near elimination of mosquitoes and works better than the pure TYC or pure SIT method. These conclusions have great significance for species controls with an XX-XY sex determinism system or ZZ-ZW system.
Aquatic invasive species specialists’ perceptions on the importance of genetic tools and concepts to inform management
22482T. A. Bernos, K. M. Jeffries and N. E. Mandrak, Biological Invasions, 24:1863-1879. 2022-05-14 07:09:36.
Perceptions related to the importance of genetic research influence the mobilization of genetic tools and concepts to inform conservation actions. Research characteristics, stakeholders’ perspectives, knowledge, and social linkages with geneticists influence the outcome of genetic information for management practices. We surveyed a broad range of aquatic invasive species (AIS) specialists whose opinions, perspectives, and decisions influence AIS decision-making. We assessed perceptions related to the importance of genetic tools and concepts, as well as the appropriateness of genetic biocontrol, and tested whether their expertise, background, and experience influenced perceptions in a predictable way. While perceptions towards genetic tools and concepts were generally heterogeneous, there was a high consensus (84%) related to the importance of eDNA. Most predictors were weakly correlated with importance ratings. Specialists’ genetic knowledge was the strongest predictor of higher importance ratings: the odds of AIS specialists giving higher ratings increased by up to 1.5-fold with increasing genetic knowledge. When evaluating the appropriateness of genetic biocontrol, level of support was lower for approaches based on gene editing (58%) than those relying on traditional hatchery techniques (70%). Support for gene editing varied by geographic location and with specialists’ knowledge of genetics and AIS management. These findings suggest that perceptions towards genetic research vary between genetic tools and concepts and are shaped by the interplay of individual’s values, expertise, experience, and background. To collaborate more effectively, genetic scientists must understand the extent of genetic knowledge of their AIS management partners and recognize that their conceptions of the conservation genetics research-practice space may vary.
The fate of a suppressed X-linked meiotic driver: experimental evolution in Drosophila simulans
22676H. Bastide, D. Ogereau, C. Montchamp-Moreau and P. R. Gérard, Chromosome Research, 2022-04-30 07:53:46.
Sex-ratio (SR) meiotic drivers are X-linked selfish genetic elements that promote their own transmission by preventing the production of Y-bearing sperm, which usually lowers male fertility. The spread of SR drivers in populations is expected to trigger the evolution of unlinked drive suppressors, a theoretically predicted co-evolution that has been observed in nature. Once completely suppressed, the drivers are expected either to decline if they still affect the fitness of their carriers, or to evolve randomly and possibly get fixed if the suppressors eliminate their deleterious effects. To explore this issue, we used the Paris sex-ratio system of Drosophila simulans in which drive results from the joint effect of two elements on the X chromosome: a segmental duplication and a deficient allele of the HP1D2 gene. We set up six experimental populations starting with 2/3 of X chromosomes carrying both elements (X(SR)) in a fully suppressing background. We let them evolve independently during almost a hundred generations under strong sexual competition, a condition known to cause the rapid disappearance of unsuppressed Paris X(SR) in previous experimental populations. In our study, the fate of X(SR) chromosomes varied among populations, from extinction to their maintenance at a frequency close to the starting one. While the reasons for these variable outcomes are still to be explored, our results show that complete suppression can prevent the demise of an otherwise deleterious X(SR) chromosome, turning a genetic conflict into cooperation between unlinked loci. Observations in natural populations suggest a contrasting fate of the two elements: disappearance of the duplication and maintenance of deficient HP1D2 alleles.
The evolutionary significance of meiotic drive
21913J. B. Searle and F. P.-M. de Villena, Heredity, 2022-04-25 08:34:39.
In this essay, we will focus on‘true meiotic drive’ where the distorted transmission does arise within meiosis itself (Zanders and Unckless2019),specifically in females. Here, the non-transmission of one of the products of meiotic division is inherent in the gametogenic process—with the formation of a polar body as the functionless by-product of division, with the egg continuing on as the viable entity. The meiotic drive is therefore the biased segregation in favour of one type of allele such that it is most commonly retained in the egg at the cost of the other type of allele, which most commonly ends up in the polar body. The biased segregation can occur at either the first or second division ofmeiosis—both of which generate a functionless polar body, suchthat there is ultimately only one viable product of the two divisions—the final version of the egg, which then becomes a zygote on fertilisation.
Trojan trout: could turning an invasive fish into a ‘super-male’ save a native species?
21823J. Miller, The Guardian, 2022-04-21 06:11:45.
Brook trout may greatly outnumber the Rio Grande cutthroat here, but nearly every brookie the team captures is male. That’s because many are a lab-produced variety known as “Trojan” brook trout. They are unique in that they carry not one, but two copies of the Y chromosome that codes maleness; they have no X chromosome to pass on. Since 2018, various streams across the Vermejo reserve have been stocked with this strain in an attempt to tilt the brook trout sex ratio so far male that eventually the population will stop breeding and die out on its own. Similar efforts are under way in a handful of creeks in Idaho, Washington and Oregon, and Nevada plans to embark on its own stocking programme this summer. Until now, the main tool to eliminate invasive fish species has been the potent chemical rotenone. The trouble is that “it also kills all the other fish, including the ones you are trying to conserve,” says Colleen Caldwell, a professor of fish and wildlife at New Mexico State University and a principal investigator overseeing the Leandro Creek project.
Propagation of seminal toxins through binary expression gene drives could suppress populations
21691J. Hurtado, S. Revale and L. M. Matzkin, Scientific Reports, 12:6332. 2022-04-15 08:22:57.
Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.
Hoisted with his own petard: how sex-ratio meiotic drive in Drosophila affnis creates resistance alleles that limit its spread
20440W.-J. Ma, K. B. Patch, E. M. Knoles, M. M. Shoaib and R. L. Unckless, bioRxiv, 2022.02.14.480432. 2022-02-16 09:24:56.
Meiotic drivers are selfish genetic elements that tinker with gameto-genesis to bias their own transmission into the next generation of off-spring. Such tinkering can have significant consequences on gameto-genesis and end up hampering the spread of the driver. In Drosophila affrnis, sex-ratio meiotic drive is caused by an X-linked complex that, when in males with a susceptible Y chromosome, results in broods that are more than 95% female. Interestingly, D. affrnis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons - effectively reversing the sex-ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 50X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex-ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex-ratio X chromosome and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex-chromosome turnover indirectly.Competing Interest StatementThe authors have declared no competing interest.
Endosymbionts moderate constrained sex allocation in a haplodiploid thrips species in a temperature-sensitive way
20394A. Katlav, D. T. Nguyen, J. L. Morrow, R. N. Spooner-Hart and M. Riegler, Heredity, 9. 2022-02-03 09:32:33.
Maternally inherited bacterial endosymbionts that affect host fitness are common in nature. Some endosymbionts colonise host populations by reproductive manipulations (such as cytoplasmic incompatibility; CI) that increase the reproductive fitness of infected over uninfected females. Theory predicts that CI-inducing endosymbionts in haplodiploid hosts may also influence sex allocation, including in compatible crosses, however, empirical evidence for this is scarce. We examined the role of two common CI-inducing endosymbionts, Cardinium and Wolbachia, in the sex allocation of Pezothrips kellyanus, a haplodiploid thrips species with a split sex ratio. In this species, irrespective of infection status, some mated females are constrained to produce extremely male-biased broods, whereas other females produce extremely female-biased broods. We analysed brood sex ratio of females mated with males of the same infection status at two temperatures. We found that at 20 degrees C the frequency of constrained sex allocation in coinfected pairs was reduced by 27% when compared to uninfected pairs. However, at 25 degrees C the constrained sex allocation frequency increased and became similar between coinfected and uninfected pairs, resulting in more male-biased population sex ratios at the higher temperature. This temperature-dependent pattern occurred without changes in endosymbiont densities and compatibility. Our findings indicate that endosymbionts affect sex ratios of haplodiploid hosts beyond the commonly recognised reproductive manipulations by causing female-biased sex allocation in a temperature-dependent fashion. This may contribute to a higher transmission efficiency of CI-inducing endosymbionts and is consistent with previous models that predict that CI by itself is less efficient in driving endosymbiont invasions in haplodiploid hosts.
Characterization of the first Wolbachia from the genus Scaptodrosophila, a male-killer from the rainforest species S. claytoni
20034K. M. Richardson, M. Schiffer, P. A. Ross, J. A. Thia and A. A. Hoffmann, Insect Science, 2022-01-12 09:30:05.
Abstract The Scaptodrosophila genus represents a large group of drosophilids with a worldwide distribution and a predominance of species in Australia, but there is little information on the presence and impacts of Wolbachia endosymbionts in this group. Here we describe the first Wolbachia infection from this group, wClay isolated from Scaptodrosophila claytoni (van Klinken), a species from the east coast of Australia. The infection is polymorphic in natural populations, occurring at a frequency of around 6%?10%. wClay causes male killing, producing female-biased lines; most lines showed 100% male killing, though in one line it was < 80%. The lines need to be maintained through the introduction of males unless the infection is removed by tetracycline treatment. wClay is transmitted at a high fidelity (98.6%) through the maternal lineage and has been stable in two laboratory lines across 24 generations, suggesting it is likely to persist in populations. The infection has not been previously described but is closely related to the male-killing Wolbachia recently described from Drosophila pandora based on MLST typing and the wsp gene. Male-killing Wolbachia are likely to be common in drosophilids but remain difficult to detect because the infections can often be at a low frequency. This article is protected by copyright. All rights reserved
Scientists Used CRISPR Gene Editing to Choose the Sex of Mouse Pups
19906S. Fan, Singuarity Hub, 2021-12-23 08:37:01.
“Do you want a boy or a girl?” can be an awkward question.But in certain circles, it’s a question that’s asked every day. Take agriculture. In a perfect world, most cows would only birth females. Chicks would grow up to be all hens. “Sexing” a farm animal when they’re at a young age wouldn’t be a thing—especially when it means male animals, without the ability to produce milk or eggs, are often culled at a young age to preserve resources. There might be a better way. This month, a team tapped into the power of CRISPR to control the sex of the offspring in mice. By splicing CRISPR components into the parents’ genome, the team was able to flip on—or off—a switch that nearly perfectly determined the sex of their litters. Unlike previous attempts, the baby mice could go on to have litters of their own of both sexes. The targeted gene used for the edit is conserved across evolution, suggesting the technique could work in more animals than just mice. But it’s controversial. Essentially, the technique selectively kills off embryos of a certain sex, which immediately raises ethical red flags. For now, scientists aren’t concerned about the technology being used in humans due to its complexity. But the study is the latest to showcase biotech’s increasing ability to manipulate reproduction.
Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive
19623S. Gamez, D. Chaverra-Rodriguez, A. Buchman, N. P. Kandul, S. C. Mendez-Sanchez, J. B. Bennett, C. H. Sánchez, T. Yang, I. Antoshechkin, J. E. Duque, P. A. Papathanos, J. M. Marshall and O. S. Akbari, Nature Communications, 7202. 2021-12-10 21:34:38.
CRISPR-based genetic engineering tools aimed to bias sex ratios, or drive effector genes into animal populations, often integrate the transgenes into autosomal chromosomes. However, in species with heterogametic sex chromsomes (e.g. XY, ZW), sex linkage of endonucleases could be beneficial to drive the expression in a sex-specific manner to produce genetic sexing systems, sex ratio distorters, or even sex-specific gene drives, for example. To explore this possibility, here we develop a transgenic line of Drosophila melanogaster expressing Cas9 from the Y chromosome. We functionally characterize the utility of this strain for both sex selection and gene drive finding it to be quite effective. To explore its utility for population control, we built mathematical models illustrating its dynamics as compared to other state-of-the-art systems designed for both population modification and suppression. Taken together, our results contribute to the development of current CRISPR genetic control tools and demonstrate the utility of using sex-linked Cas9 strains for genetic control of animals.
Gene editing used to create all-male or all-female litters of mice
19542J. Goodyer, Science Focus, 2021-12-06 20:26:39.
As males are unable to produce milk or lay eggs, the ability to breed cows and hens that produce all-female litters is likely to be high on most poultry and dairy farmers’ wish lists. Now, scientists at the Francis Crick Institute and the University of Kent have come a step closer to realising this goal after successfully using CRISPR gene editing techniques to produce all-female or all-male litters of mice. The technique could also be used to improve animal welfare in areas of scientific research in which only male or only female animals are required for studies, the researchers say. To make the breakthrough the researchers took advantage of the fact that CRISPR consists of two parts – the Cas9 enzyme, which cuts the DNA and enables scientists to alter specific regions of genes, and the guide RNA, which carries the Cas9 enzyme to the desired region on the genome.
Gene editing used to create all-male or all-female mice litters
19502A. Reis, European Scientist, 2021-12-04 17:04:50.
Researchers from the Francis Crick Institute and the University of Kent used gene-editing technologies to create male-only and female-only mice litters, according to a study published in Nature Communications (1). The authors also suggested ways in which this method could be used to improve animal welfare in scientific research and agriculture. There are many situations in research and agriculture where it would be desirable to have just females or just males. For example, reproductive studies require only animals of the gender being studied, while in farming, egg and milk production needs only female animals. Sadly, in many cases, the unwanted animals end up being culled. “This work could have an immediate and valuable impact in scientific laboratories, as we’ve shown how it is safe and effective in mice, a common mammal used in medical and scientific research. While a lot of research needs both sexes, there are areas of study where only one is needed. For example, when studying the reproductive system, sex-specific diseases, or certain hormones”, said James Turner, group leader of the Sex Chromosome Biology Laboratory at the Crick says:
Gene-editing used to create single sex mice litters
19504The Francis Crick Institute, Phys Org, 2021-12-03 17:09:04.
Scientists at the Francis Crick Institute, in collaboration with University of Kent, have used gene editing technology to create female-only and male-only mice litters with 100% efficiency. This proof of principle study, published in Nature Communications today, demonstrates how the technology could be used to improve animal welfare in scientific research and perhaps also agriculture. In scientific research and also farming, there is often a need for either male or female animals. For example, laboratory research into male or female reproduction requires only animals of the sex being studied. And in farming, only female animals are required for egg production and in dairy herds. This means it is common practice for animals of the unrequired sex to be culled after birth. The researchers' new method uses a two-part genetic system to inactivate embryos shortly after fertilisation, allowing only the desired sex to develop. Such a genetically-based method to control the sex of offspring could drastically reduce culling in both industries. The embryo selection is based on the fact that there are two elements of CRISPR-Cas9—the Cas9 enzyme that cuts the DNA, allowing scientists to alter specific regions, and the guide RNA which carries the Cas9 to the right location on the genome. The team placed one element of the system on the father's X or Y chromosome, meaning that it will only be inherited by female or male embryos respectively. The other element is contributed by the mother, and is inherited by all embryos.
Single-sex mice litters were created with 100% efficiency using gene editing.
19498R. Silman, Brinkwire, 2021-12-03 17:00:12.
The Francis Crick Institute, in partnership with the University of Kent, has employed gene editing technology to construct 100% efficient female-only and male-only mouse litters. This proof-of-concept study, which was published today (Friday, December 3rd, 2021) in Nature Communications, shows how the technique could be used to improve animal wellbeing in scientific research and possibly agriculture. Male and female animals are frequently required in scientific research and husbandry. Laboratory research into male or female reproduction, for example, necessitates only animals of the examined sex. In addition, only female animals are needed for egg production and dairy herds in farming. This means that animals of the unrequired sex are routinely culled after birth.
Lab animals: Gene-editing technology is used to create female-only and male-only mice litters
19493todayuknews, Today UK News, 2021-12-03 16:50:32.
Single-sex litters of mice — comprising only either female or male pups — have been produced by means of so-called CRISPR-Cas9 gene editing technology. The technique, developed by experts at the Francis Crick Institute and the University of Kent, works by inactivating embryos of one sex shortly after fertilisation. It could be used to improve animal welfare in both laboratory and agricultural settings where, for various reasons, only female or male animals are needed. It is common for animals of the unrequired sex to be culled — a practice which could be drastically reduced by controlling the sex of the animals prior to birth. As the technique requires the genetic modification of both parents to work, however, the approach would not be suitable for forcing the sex of designer babies. Single-sex litters of mice — comprising only either female or male pups — have been produced by means of so-called CRISPR-Cas9 gene editing technology. Pictured: the mice that were bred to create single-sex litters. The black parts of their coat are caused by the genetically modified cells, while the white parts come from the non-modified parts of their genome
Gene editing produces all-male or all-female litters of mice
19491E. Pennisi, Science, 2021-12-03 16:41:41.
In some farmers’ ideal world, cows would birth only females, sows would bear no boars, and chicks would all grow up to be hens. Such sex ratios would stop them from killing millions of male animals, which don’t produce eggs or milk. Now, scientists are a step closer to this reality. Researchers have harnessed the gene editor CRISPR to produce litters of mice all of one sex. That’s a potential boon to agriculture and may offer a more immediate advantage in scientific research. “The paper shows a state-of-the-art solution to producing single-sex species,” with “impressive results,” says Ehud Qimron, a CRISPR expert at Tel Aviv University who was not involved with the work. The impact for lab animals may be huge. “In the past 5 years around 25,000 papers were published using mice in sex-specific research studies,” says study co-author James Turner, a molecular geneticist at the Francis Crick Institute. “If we could prevent the generation of the unstudied sex, the number [saved] would be in the hundreds of thousands.” Other methods exist to skew the male/female ratio of newborn animals. Scientists can sort sperm by the weight of the sex chromosome, or cause embryos of one sex to die before birth. In a study published 2 years ago, researchers using the gene editor CRISPR managed to produce altered mice in which four of five litters were all female.
CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes
19469C. Douglas, V. Maciulyte, J. Zohren, D. M. Snell, S. K. Mahadevaiah, O. A. Ojarikre, P. J. I. Ellis and J. M. A. Turner, Nature Communications, 12:6926. 2021-12-03 15:06:30.
Animals are essential genetic tools in scientific research and global resources in agriculture. In both arenas, a single sex is often required in surplus. The ethical and financial burden of producing and culling animals of the undesired sex is considerable. Using the mouse as a model, we develop a synthetic lethal, bicomponent CRISPR-Cas9 strategy that produces male- or female-only litters with one hundred percent efficiency. Strikingly, we observe a degree of litter size compensation relative to control matings, indicating that our system has the potential to increase the yield of the desired sex in comparison to standard breeding designs. The bicomponent system can also be repurposed to generate postnatal sex-specific phenotypes. Our approach, harnessing the technological applications of CRISPR-Cas9, may be applicable to other vertebrate species, and provides strides towards ethical improvements for laboratory research and agriculture.
Propagation of seminal toxins through binary expression gene drives can suppress polyandrous populations
19953J. Hurtado, S. Revale and L. M. Matzkin, bioRxiv, 2021.11.23.469777. 2021-11-24 09:48:59.
Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.Competing Interest StatementThe authors have declared no competing interest.
Satellite DNA-mediated diversification of a sex-ratio meiotic drive gene family in Drosophila
18354C. A. Muirhead and D. C. Presgraves, Nature Ecology & Evolution, 2021-09-06 14:01:24.
Sex chromosomes are susceptible to the evolution of selfish meiotic drive elements that bias transmission and distort progeny sex ratios. Conflict between such sex-ratio drivers and the rest of the genome can trigger evolutionary arms races resulting in genetically suppressed ‘cryptic’ drive systems. The Winters cryptic sex-ratio drive system of Drosophila simulans comprises a driver, Distorter on the X (Dox) and an autosomal suppressor, Not much yang, a retroduplicate of Dox that suppresses via production of endogenous small interfering RNAs (esiRNAs). Here we report that over 22 Dox-like (Dxl) sequences originated, amplified and diversified over the ~250,000-year history of the three closely related species, D. simulans, D. mauritiana and D. sechellia. The Dxl sequences encode a rapidly evolving family of protamines. Dxl copy numbers amplified by ectopic exchange among euchromatic islands of satellite DNAs on the X chromosome and separately spawned four esiRNA-producing suppressors on the autosomes. Our results reveal the genomic consequences of evolutionary arms races and highlight complex interactions among different classes of selfish DNAs.
Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population
17511B. A. Haines, F. Barradale and B. L. Dumont, bioRxiv, 2021-06-23 14:26:09.
In species with single-locus chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, are not fully mediated by maternal effects, and are not explained by sex-biased neonatal mortality. SRD exhibits a heritable component, but QTL mapping analyses and targeted investigations of sex determination genes fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We speculate that the genetic shuffling of eight diverse parental genomes during the early CC breeding generations led to the decoupling of sex-linked drivers from their co-evolved suppressors, unleashing complex, multiallelic systems of sex chromosome drive. Consistent with this interpretation, we show that several CC strains exhibit copy number imbalances at co-evolved X- and Y-linked ampliconic genes that have been previously implicated in germline genetic conflict and SRD in house mice. Overall, our findings reveal the pervasiveness of SRD in the CC population and nominate the CC as a powerful resource for investigating sex chromosome genetic conflict in action.
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.
Converting female mosquitoes to non-biting males with implications for mosquito control
15614M. V. Candy, Vet Candy, 2020-12-18 15:57:05.
Virginia Tech researchers have proven that a single gene can convert female Aedes aegypti mosquitoes into fertile male mosquitoes and identified a gene needed for male mosquito flight. Male mosquitoes do not bite and are unable to transmit pathogens to humans. Female mosquitoes, on the other hand, are able to bite. Female Aedes aegypti mosquitoes require blood to produce eggs, making them the prime carriers of the pathogens that cause Zika and dengue fever in humans. "The presence of a male-determining locus (M locus) establishes the male sex in Aedes aegypti and the M locus is only inherited by the male offspring, much like the human Y chromosome," said Zhijian Tu, a professor in the Department of Biochemistry in the College of Agriculture and Life Sciences. "By inserting Nix, a previously discovered male-determining gene in the M locus of Aedes aegypti, into a chromosomal region that can be inherited by females, we showed that Nix alone was sufficient to convert females to fertile males. This may have implications for developing future mosquito control techniques." These findings were published in the Proceedings of the National Academy of Sciences.
Polyandry blocks gene drive in a wild house mouse population
15390A. Manser, B. Konig and A. K. Lindholm, Nature Communications, 11:8. 2020-12-11 14:12:22.
Here, we study the impact of polyandry on a well-known gene drive, called t haplotype, in an intensively monitored population of wild house mice. First, we show that house mice are highly polyandrous: 47% of 682 litters were sired by more than one male. Second, we find that drive-carrying males are particularly compromised in sperm competition, resulting in reduced reproductive success. As a result, drive frequency decreased during the 4.5 year observation period. Overall, we provide the first direct evidence that the spread of a gene drive is hampered by reproductive behaviour in a natural population.
X-linked meiotic drive can boost population size and persistence
16876C. Mackintosh, A. Pomiankowski and M. F. Scott, Genetics, 217:11. 2020-12-10 14:26:46.
Here, we find general conditions for the spread and fixation of X-linked alleles. Our conditions show that the spread of X-linked alleles depends on sex-specific selection and transmission rather than the time spent in each sex. Applying this logic to meiotic drive, we show that polymorphism is heavily dependent on sperm competition induced both by female and male mating behavior and the degree of compensation to gamete loss in the ejaculate size of drive males. We extend these evolutionary models to investigate the demographic consequences of biased sex ratios. Our results suggest driving X-alleles that invade and reach polymorphism (or fix and do not bias segregation excessively) will boost population size and persistence time by increasing population productivity, demonstrating the potential for selfish genetic elements to move sex ratios closer to the population-level optimum. However, when the spread of drive causes strong sex-ratio bias, it can lead to populations with so few males that females remain unmated, cannot produce offspring, and go extinct. This outcome is exacerbated when the male mating rate is low. We suggest that researchers should consider the potential for ecologically beneficial side effects of selfish genetic elements, especially in light of proposals to use meiotic drive for biological control.
Cellular mechanisms regulating synthetic sex ratio distortion in the Anopheles gambiae germline
14790R. E. Haghighat-Khah, A. Sharma, M. R. Wunderlich, G. Morselli, L. A. Marston, C. Bamikole, A. Hall, N. Kranjc, C. Taxiarchi, I. Sharakhov and R. Galizi, Pathogens and Global Health, 114:370-378. 2020-10-20 20:24:19.
Meiotic cleavage of rDNA repeats, located in the sex chromosomes of A. gambiae SD males, affects the competitiveness of mature sperm to fertilize the female oocyte.
Selfish genetic elements and male fertility
15183R. L. Verspoor, T. A. R. Price and N. Wedell, Philosophical Transactions of the Royal Society B-Biological Sciences, 375:7. 2020-10-20 14:40:03.
Selfish genetic elements (SGEs) are diverse and near ubiquitous in Eukaryotes and can be potent drivers of evolution. Here, we discuss SGEs that specifically act on sperm to gain a transmission advantage to the next generation. The diverse SGEs that affect sperm often impose costs on carrier males, including damaging ejaculates, skewing offspring sex ratios and in particular reducing sperm-competitive success of SGE-carrying males. How males and females tolerate and mitigate against these costs is a dynamic and expanding area of research. The intense intra-genomic conflict that these selfish elements generate could also have implications for male fertility and spermatogenesis more widely. This article is part of the theme issue 'Fifty years of sperm competition'.
Assessing the acoustic behaviour of Anopheles gambiae (s.l.) dsxF mutants: implications for vector control
14647M. P. Su, M. Georgiades, J. Bagi, K. Kyrou, A. Crisanti and J. T. Albert, Parasites and Vectors, 13:507. 2020-10-07 13:33:23.
We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae (s.l.) cages.
Resistance to natural and synthetic gene drive systems
14468T. A. R. Price, N. Windbichler, R. L. Unckless, A. Sutter, J.-N. Runge, P. A. Ross, A. Pomiankowski, N. L. Nuckolls, C. Montchamp-Moreau, N. Mideo, O. Y. Martin, A. Manser, M. Legros, A. M. Larracuente, L. Holman, J. Godwin, N. Gemmell, C. Courret, A. Buc, Journal of Evolutionary Biology, 2020-09-24 17:20:31.
This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in genera
Generating single-sex litters: development of CRISPR-Cas9 genetic tools to produce all-male offspring
14343C. Douglas, V. Maciulyte, J. Zohren, D. M. Snell, O. A. Ojarikre, P. J. Ellis and J. M. A. Turner, bioRxiv, 2020.09.07.285536. 2020-09-07 18:52:30.
Using the mouse as a model, we developed a synthetic, two-part bicomponent strategy for generating all-male litters.
Mixed knobs in corn cobs
14581P. Lamelza and M. A. Lampson, Genes and Development, 34:1110-1112. 2020-08-20 14:31:38.
In this issue of Genes & Development, Swentowsky and colleagues (pp. 1239-1251) show that two types of knobs, those composed of 180-bp and TR1 sequences, recruit their own novel and divergent kinesin-14 family members to form neocentromeres.
Distinct kinesin motors drive two types of maize neocentromeres
14578K. W. Swentowsky, J. I. Gent, E. G. Lowry, V. Schubert, X. Ran, K. F. Tseng, A. E. Harkess, W. H. Qiu and R. K. Dawe, Genes and Development, 34:1239-1251. 2020-08-20 14:24:50.
Here we describe a second kinesin-14 gene, TR-1 kinesin (Trkin), that is required to mobilize neocentromeres made up of the minor tandem repeat TR-1.
Towards Responsive Eco-technology: The Development of a Male Sex-biased Mouse
24607W. Kamau, Massachusetts Institute of Technology, 2020-08-16 08:55:45.
CRISPR-Cas systems have catalyzed the emergence of several synthetic population management strategies, like gene drives, for controlling pests and disease vectors. As these technologies garner greater visibility in both general and regulatory audiences, questions have arisen about the invasiveness of drive strategies and have underscored a need for community guidance in designing population management technologies. In heterogametic species, an engineered male-determining chromosome can serve as a method for providing robust and localized population suppression without the need for a gene drive. In mice, X-chromosome inactivation is mediated by X-inactive specific transcript (Xist) long non-coding RNA. I propose to encode a system on the Y chromosome to knock out a necessary region for proper X-inactivation in females. Loss of Xist gene function has no known effects in males or females with a dysfunctional maternal copy, however, females who inherit a dysfunctional paternal copy die at embryonic day 8.5. Thus, this results in a male sex-biased mouse. To create a daughterless mouse, my proof-of-principle design will include a constitutively expressed Cas protein with at minimum a two-guide array. Additionally, I will draw on the ecological species concept found in some cultures, like the M¯aori of New Zealand, to create an alternate eco-cisgenic version using cisgenic murine elements and a CRISPR system found in a commensal species of bacteria. Creating a cisgenic non-driving mammalian model of a genetic population suppression system would be a first-of-its-kind example to show how biological engineering design decisions can be congruent with culturally specific notions of ecology.
Meet Cosmo, the gene-edited Crispr calf
13590S. D. McClain, Capital Press, 2020-07-31 12:56:28.
Cosmo was the grand finale of a series of experiments to create a line of genome-edited cattle tailored for the beef industry. He was designed to produce 75% male offspring.
Extensive Recombination Suppression and Epistatic Selection Causes Chromosome-Wide Differentiation of a Selfish Sex Chromosome in Drosophila pseudoobscura
14296Z. L. Fuller, S. A. Koury, C. J. Leonard, R. E. Young, K. Ikegami, J. Westlake, S. Richards, S. W. Schaeffer and N. Phadnis, Genetics, 216:205. 2020-07-30 14:22:50.
Here, we conduct a multifaceted study of the multiply inverted Drosophila pseudoobscura SR chromosome to understand the evolutionary history, genetic architecture, and present-day dynamics that shape this enigmatic selfish chromosome.
The future of beef might be a sausage fest
13479N. Johnson, grist, 2020-07-24 21:00:33.
N. Johnson. (2020) grist. A media report on the creation of a cow with a sex ratio altering genetic change expected to lead to 3/4 of the cow's offspring being males. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
Meet Cosmo the Frankenbull: Scientists genetically engineer a bull calf so that 75 per cent of its offspring will be male
13476J. Pinkstone, Daily Mail, 2020-07-24 20:58:14.
J. Pinkstone (2020). Daily Mail. A media report on the creation of a cow with a sex ratio altering genetic change expected to lead to 3/4 of the cow's offspring being males. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
A Crispr calf is born. It’s definitely a boy
13454M. Molteni, WIRED, 2020-07-24 16:25:14.
M. Molteni (2020). Wired. UC Davis scientists spent years editing a sex-determining gene into bovine embryos. In April, Cosmo arrived—and his DNA reveals how far the field has to go. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
Meet the first genetically modified bull. Why did scientists change it
13473J. Kessler, Free News, 2020-07-23 20:52:51.
J. Kessler (2020). Free News. UC Davis scientists have successfully introduced a bovine embryo, or the bovine SRY gene, which is responsible for the development of the male. This is the first demonstration of targeted gene insertion for large DNA sequences through embryo-mediated genome editing in cattle. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
Scientists use CRISPR technology to insert sex-determining gene
13452A. Quinton, Phys Org, 2020-07-23 16:21:10.
A. Quinton (2020). Phys Org. Scientists at the University of California, Davis, have successfully produced a bull calf, named Cosmo, who was genome-edited as an embryo so that he'll produce more male offspring. The research was presented in a poster on July 23 at the American Society of Animal Science meeting. This type of sex ratio distortion results in gene drive and is also being considered to help control populations of invasive mammals.
Tackling Dengue fever by turning female mosquitoes into males
13482T. Sandle, DIGTAL JOURNAL, 2020-07-22 21:00:41.
T. Sandle (2020). DIGTAL JOURNAL Genetic engineering appears to be the key for delivering mosquito control, according to new research. Scientists have successfully converted female mosquitoes into non-biting males.
Genetic Biocontrol for Invasive Species
11964J. L. Teem, L. Alphey, S. Descamps, M. P. Edgington, O. Edwards, N. Gemmell, T. Harvey-Samuel, R. L. Melnick, K. P. Oh, A. J. Piaggio, J. R. Saah, D. Schill, P. Thomas, T. Smith and A. Roberts, Frontiers in Bioengineering and Biotechnology, 8:452. 2020-05-25 18:12:26.
Invasive species are increasingly affecting agriculture, food, fisheries, and forestry resources throughout the world. As a result of global trade, invasive species are often introduced into new environments where they become established and cause harm to human health, agriculture, and the environment. Prevention of new introductions is a high priority for addressing the harm caused by invasive species, but unfortunately efforts to prevent new introductions do not address the economic harm that is presently manifested where invasive species have already become established. Genetic biocontrol can be defined as the release of organisms with genetic methods designed to disrupt the reproduction of invasive populations. While these methods offer the potential to control or even eradicate invasive species, there is a need to ensure that genetic biocontrol methods can be deployed in a way that minimizes potential harm to the environment. This review provides an overview of the state of genetic biocontrol, focusing on several approaches that were the subject of presentations at the Genetic Biocontrol for Invasive Species Workshop in Tarragona, Spain, March 31st, 2019, a workshop sponsored by the OECD’s Co-operative Research Program on Biological Resource Management for Sustainable Agricultural Systems. The review considers four different approaches to genetic biocontrol for invasive species; sterile-release, YY Males, Trojan Female Technique, and gene drive. The different approaches will be compared with respect to the efficiency each affords as a genetic biocontrol tool, the practical utility and cost/benefits associated with implementation of the approach, and the regulatory considerations that will need to be addressed for each. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its Member countries.
Hope rises as scientists eliminate malaria mosquitoes
11953A. Adeyemi, New Telegraph, 2020-05-14 17:57:14.
A team of researchers led by Imperial College London have spread a genetic modification that distorted the sex ratio through a population of caged Anopheles gambiae mosquitoes using ‘gene drive’ technology. According to the results of their study published yesterday in ‘Nature Biotechnology,’ the modification they initiated in the laboratory created more male offspring that was able to eliminate populations of malaria mosquitoes in the lab experiments.
Malaria mosquitoes eliminated in lab by creating all-male offsprings
11945Aishwarya, Inshorts, 2020-05-13 17:53:53.
Imperial College London-led team used 'gene drive' technology to spread genetic modification that distorted sex ratio through caged breed of malaria mosquitoes. This caused mosquitoes to produce more male offspring, eventually leading to no female birth. The study suggested such mosquitoes carrying a sex-distorter gene drive could help spread male bias within local malaria-carrying populations.
Researchers use “gene drive” technology to eliminate malaria mosquitoes in lab experiments
11619J. Ives, News Medical Life Sciences, 2020-05-13 16:15:18.
A team led by Imperial College London spread a genetic modification that distorts the sex ratio through a population of caged Anopheles gambiae mosquitoes using 'gene drive' technology.
Genetically-manipulated male mosquitoes could eliminate females
11617B. Coxworth, New Atlas, 2020-05-13 16:13:30.
Several years ago, we heard how scientists were looking at eradicating malaria-carrying mosquitoes by making the females infertile. Now they're going a step further, by eliminating the females altogether.
Researchers discover way to eliminate malaria carrying mosquitoes
11615S. Digon, International Business Times, 2020-05-13 16:12:04.
Researchers from the Imperial College London have come up with a genetic modification that will pave the way for the elimination of malaria mosquitoes. Scientists say that the alteration distorts the sex ratio of caged Anopheles gambiae mosquitoes using what they call a ‘gene drive’ technology.
The malaria mosquito is eliminated in the lab by creating a population of all males
11611NewsDesk, Instant, 2020-05-11 16:08:42.
A team led by Imperial College London disseminates genetic modification that distorts the sex ratio through the Anopheles gambiae mosquito population that is locked up using ‘gene drive’ technology.
Malaria mosquitoes eliminated in lab by creating all male populations
11609H. Dunning, Imperial College London, 2020-05-11 16:07:00.
A team led by Imperial College London spread a genetic modification that distorts the sex ratio through a population of caged Anopheles gambiae mosquitoes using ‘gene drive’ technology.
Gene editing could fight malaria by causing only male mosquitos to be born
11958L. Dormehl, Digital Trends, 2020-04-14 18:01:16.
What’s the theoretically easiest way to ensure that a population of mosquitos is not able to sustain itself through breeding? Make sure that there aren’t enough females, of course. That’s the exploratory approach being pioneered by researchers at the U.K.’s Imperial College London, who have developed a way of distorting the sex ratio in species of Anopheles gambiae mosquitoes to ensure that offspring are predominantly male. Over a relatively short period of time, this causes the population of mosquitos to collapse — and, potentially, halts one of the main vectors for spreading diseases like malaria as a result.
Simulating effects of fitness and dispersal on the use of Trojan sex chromosomes for the management of invasive species
11488C. C. Day, E. L. Landguth, R. K. Simmons, W. P. Baker, A. R. Whiteley, P. M. Lukacs and A. Bearlin, Journal of Applied Ecology, 2020-03-19 20:15:27.
The use of Trojan Y chromosomes (TYC) for controlling invasive species involves manipulating the sex chromosomes of captive-raised individuals. Following release, the offspring of these individuals consist of only one sex, thereby skewing the sex ratio of the invasive population and potentially leading to eradication. Simulation models are needed that can inform managers about how to maximize the likelihood of invasive species eradication, since implementation of this novel management approach in the field is still rare. Here, we present the first spatially explicit, mechanistic simulation model of a real-world TYC program for invasive species eradication. Using a brook trout Salvelinus fontinalis system model, we investigated the effects of competitive and reproductive fitness of the captive-raised YY males, dispersal behaviour upon their release and landscape heterogeneity on eradication success. Likelihood of eradication was dependent on both the competitive and reproductive fitness of the Trojan individuals. Competitive fitness (i.e. survival) had a higher threshold for eradication, below which the invasive populations were not eradicated. Movement ecology of both the wild and YY male populations was important for eradication. Under a restricted dispersal scenario for YY males following their release, the wild population was not extirpated but maintained a stable, yet reduced, population size. Analysis of landscape configuration indicated that time to eradication of local patches increased with greater connectivity within the stream network. In addition to sex ratio distortion, density-dependent mortality resulting from outplantings made an important contribution to population decline and therefore may also affect native competitors. Synthesis and applications. The use of Trojan sex chromosomes to skew population sex ratios is a novel method for the suppression and eradication of aquatic invasive species. Results from our modelling work indicate that while eradication is possible, maximizing its likelihood requires an understanding of the fitness and movement ecology of both the wild and YY male populations of the invasive species. Both our model and the principles derived from this study related to fitness and behavioural landscape ecology can be broadly applied to other invaded species and systems.
Autosomal suppression and fitness costs of an old driving X chromosome in Drosophila testacea
7363G. Keais, S. Lu and S. Perlman, Journal of Evolutionary Biology, 2020-01-28 21:58:18.
Driving X chromosomes (XDs) are meiotic drivers that bias their own transmission through males by killing Y-bearing gametes. These chromosomes can in theory spread rapidly in populations and cause extinction, but many are found as balanced polymorphisms or as ?cryptic? XDs shut down by drive suppressors. The relative likelihood of these outcomes, as well as the evolutionary pathways through which they come about, are not well-understood. An XD was recently discovered in the mycophagous fly, Drosophila testacea, presenting the opportunity to compare this XD with the well-studied XD of its sister species, Drosophila neotestacea. Comparing features of independently evolved XDs in young sister species is a promising avenue towards understanding how XDs and their counteracting forces change over time. In contrast to the XD of D. neotestacea, we find that the XD of D. testacea is old, with its origin predating the radiation of three species: D. testacea, D. neotestacea, and their shared sister species, Drosophila orientacea. Motivated by the suggestion that older XDs should be more deleterious to carriers, we assessed the effect of the XD on both male and female fertility. Unlike what is known from D. neotestacea, we found a strong fitness cost in females homozygous for the XD in D. testacea: a large proportion of homozygous females failed to produce offspring after being housed with males for several days. Our male fertility experiments show that while XD male fertility is lower under sperm depleting conditions, XD males have comparable fertility to males carrying a standard X chromosome under a free mating regime, which may better approximate conditions in wild populations of D. testacea. Lastly, we demonstrate the presence of autosomal suppression of X chromosome drive. Our results provide support for a model of XD evolution where the dynamics of young XDs are governed by fitness consequences in males, whereas in older XD systems, both suppression and fitness consequences in females likely supersede male fitness costs.
Optimal control and analysis of a modified trojan Y-Chromosome strategy
11491M. A. Beauregard, R. D. Parshad, S. Boon, H. Conaway, T. Griffin and J. J. Lyu, Ecological Modelling, 416. 2020-01-15 20:19:52.
The Trojan Y Chromosome (TYC) strategy is a promising eradication method that attempts to manipulate the female to male ratio to promote the reduction of the population of an invasive species. The manipulation stems from an introduction of sex-reversed males, called supermales, into an ecosystem. The offspring of the supermales is guaranteed to be male. Mathematical models have shown that the population can be driven to extinction with a continuous supply of supermales. In this paper, a new model of the TYC strategy is introduced and analyzed that includes two important modeling characteristics, that are neglected in all previous models. First, the new model includes intraspecies competition for mates. Second, a strong Allee effect is included. Several conclusions about the strategy via optimal control are established. These results have large scale implications for the biological control of invasive species.
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.
Standard deviations: The biological bases of transmission ratio distortion
6179L. Fishman and M. McIntosh, Annual Review of Genetics, 53:347-372. 2019-09-10 18:59:40.
The rule of Mendelian inheritance is remarkably robust, but deviations from the equal transmission of alternative alleles at a locus [a.k.a. transmission ratio distortion (TRD)] are also commonly observed in genetic mapping populations. Such TRD reveals locus-specific selection acting at some point between the diploid heterozygous parents and progeny genotyping and therefore can provide novel insight into otherwise-hidden genetic and evolutionary processes. Most of the classic selfish genetic elements were discovered through their biasing of transmission, but many unselfish evolutionary and developmental processes can also generate TRD. In this review, we describe methodologies for detecting TRD in mapping populations, detail the arenas and genetic interactions that shape TRD during plant and animal reproduction, and summarize patterns of TRD from across the genetic mapping literature. Finally, we point to new experimental approaches that can accelerate both detection of TRD and characterization of the underlying genetic mechanisms.
The association between mitochondrial genetic variation and reduced colony fitness in an invasive wasp
13731J. Dobelmann, A. Alexander, J. W. Baty, N. J. Gemmell, M. A. M. Gruber, O. Quinn, T. Wenseleers and P. J. Lester, Molecular Ecology, 28:3324-3338. 2019-06-24 19:25:29.
Despite the mitochondrion's long-recognized role in energy production, mitochondrial DNA (mtDNA) variation commonly found in natural populations was assumed to be effectively neutral. However, variation in mtDNA has now been increasingly linked to phenotypic variation in life history traits and fitness. We examined whether the relative fitness in native and invasive common wasp (Vespula vulgaris) populations in Belgium and New Zealand (NZ), respectively, can be linked to mtDNA variation.
Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection on Islands: Workshop Report
11581M. Farooque, S. K. Barnhill-Dilling, J. Shapiro and J. Delborne, North Carolina State University, 2019-06-01 15:28:38.
The “Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection” workshop was held on the North Carolina State University campus in Raleigh, NC on March 7-8, 2019, aiming to convene a diverse group of stakeholders, scientists, funders, and leaders for an exploration of perspectives on the development of a gene drive mouse for restoring biodiversity on islands. Information collected at the workshop is presented in this report to inform upcoming decisions by the NCSU-Safe Genes research team about research, testing, and potential deployment of technologies (the Safe Genes program does not fund any environmental releases of gene drive modified organisms), as well as future engagement activities.
Genetic pest management technologies to control invasive rodents
11576D. Kanavy and D. Threadgill, Island invasives: scaling up to meet the challenge, 2019-03-05 15:20:05.
Many strategies exist to manage invasive pests on islands, ranging from poison to trapping, with varying degrees of success. Genetic technologies are increasingly being applied to insect pests, but so far, not to vertebrates. We are implementing a genetic strategy to eradicate invasive mouse populations as another tool for pest control. Mus musculus, the common house mouse, is one of the most widespread invasive species. Mice threaten human health, agriculture, and biodiversity on many islands, particularly seabirds. Seabirds are endangered indirectly through competition for resources or predators being attracted by the mice or directly with mice attacking chicks and eggs. Rodenticides are the most common method of eradicating mice, but their use leads to poisoning of non-target species and has limited efficacy against mice. An approach that could eliminate non-target species impact would be to engineer daughterless mice linked to a gene drive system for self-sustained propagation. For this project, we have investigated exploiting a naturally occurring gene drive, the t-complex. Using the t w2 haplotype of the t-complex, we observed the t w2 haplotype being transmitted to offspring with a transmission distortion ratio of 95.3%. The daughterless phenotype is being accomplished by inserting the Sry gene (male sex-determining gene) into an autosome containing the tw2 haplotype via CRISPR/Cas9 gene editing. The presence of Sry will induce testis formation, regardless of the sex chromosomes naturally inherited. When Sry is inserted into the t-complex, the desired gene will spread through the population, eliminating female offspring. This model system will support studies to evaluate the effectiveness of crashing an invasive population without adversely affecting other
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.
Transmission ratio distortion is frequent in Arabidopsis thaliana controlled crosses
3942Seymour, DKC, E.; Arioz, B. I.; Koenig, D.; Weigel, D., Heredity, 122:294-304. 2019-01-20 00:00:00.
The equal probability of transmission of alleles from either parent during sexual reproduction is a central tenet of genetics and evolutionary biology. Yet, there are many cases where this rule is violated. The preferential transmission of alleles or genotypes is termed transmission ratio distortion (TRD). Examples of TRD have been identified in many species, implying that they are universal, but the resolution of species-wide studies of TRD are limited. We have performed a species-wide screen for TRD in over 500 segregating F-2 populations of Arabidopsis thaliana using pooled reduced-representation genome sequencing. TRD was evident in up to a quarter of surveyed populations. Most populations exhibited distortion at only one genomic region, with some regions being repeatedly affected in multiple populations. Our results begin to elucidate the species-level architecture of biased transmission of genetic material in A. thaliana, and serve as a springboard for future studies into the biological basis of TRD in this species.
Population Consequences of Releasing Sex-Reversed Fish: Applications and Concerns
11500C. Wederkind, Sex Control in Aquaculture, Chp 8:179-188. 2018-11-02 20:38:44.
Sex differentiation is generally more labile in gonochoristic fish than it is, for example, in birds and mammals. Environmentally induced sex reversal is, therefore, often possible, and creates genotype‐phenotype mismatches that can be useful in population management. Interestingly, sex chromosomes of fish are typically not significantly decayed (i.e., all types of offspring of sex‐reversed individuals may be viable, including YY and WW individuals that can then often be sex reversed again). Releasing sex‐reversed fish, or releasing untreated YY and WW offspring of sex‐reversed fish, into natural populations can, therefore, affect the sex ratio of the population in the following generations and, hence, affect population growth.
Sex Control in Aquaculture: Concept to Practice
11497H.P. Wang and Z.G. Shen, Sex Control in Aquaculture, 2018-11-02 20:26:50.
Understanding sex determining (SD) mechanisms and related concepts in a wide range of fish species is critical for sex control and large‐scale monosex production in aquaculture, in which monosex culture is superior to mixed‐sex culture. Establishment of phenotypic sex is triggered by SD factor(s), modulated by complex molecular networks, and influenced by environmental conditions, steroid hormones, and endocrine disrupting chemicals. Temperature‐dependent sex determination (TSD) presents in fish, and the feature has been applied to monosex production in several fish species, since many downstream aspects of TSD are shared with genotypic sex determination (GSD). Although SD genes have been identified in some fish, the complex molecular networks involved in sex differentiation remain unclear. Large‐scale monosex production could be achieved in the third generation with sex‐linked markers (SLMs), and in the fourth generation with no available SLMs in fish with a XY or ZW SD mode. There is a great potential for producing large‐scale breeding systems for females in much less time if gynogenesis and sex reversal of XX‐females are combined. In addition, atypical genotypes (YY and WW) have the potential to serve as a biological tools to control invasive species in natural waters. In this chapter, we briefly review the concepts and practices of sex control in fish and aquaculture, based on the achievements during the past two decades.
Invasion Success and Management Strategies for Social Vespula Wasps
13740P. J. Lester and J. R. Beggs, Annual Review of Entomology, 64:51-71. 2018-09-26 19:38:03.
Three species of Vespula have become invasive in Australia, Hawai'i, New Zealand, and North and South America and continue to spread. Economically, their main negative effect is associated with pollination and the apicultural industry. Climate change is likely to exacerbate their impacts in many regions. Although investigated extensively, no effective biological control agents have yet been found. Emerging technologies such as gene drives are under consideration.
A spatially discrete, integral projection model and its application to invasive carp
11503R. A. Erickson, E. A. Eager, P. M. Kocovsky, D. C. Glover, J. L. Kallis and K. R. Long, Ecological Modelling, 387:163-171. 2018-09-21 20:46:26.
Natural resource managers and ecologists often desire an understanding of spatial dynamics such as migration, dispersion, and meta-population dynamics. Network-node models can capture these salient features. Additionally, the state-variable used with many species may be appropriately modeled as a continuous variable (e.g., length) and management activities sometimes can only target individuals of certain sizes. Integral projection models (IPMs) can capture this life history characteristic and allow for the examination of size-specific management. We combined an IPM with a network-node model to capture both of these salient features. We then demonstrated how this model could be used to understand and manage populations of invasive species focusing on grass carp as an example. Grass carp disrupt ecosystems outside of their native range and have spread around much of the world, including North America. The impacts of grass carp include adversely changing aquatic plant communities, which in turn affect a wide range of endpoints ranging from water quality to waterfowl recruitment. We specifically examined two theoretical systems using parameters from the literature. First, we modeled a lake with two tributaries and examined how modified sterile males could be used as a control tool. We found that modified sterile males may be a feasible control tool to limit population growth. Second, we modeled a series of river pools and examined how harvest and deterrents could be used to decrease the risk of expanding grass carp's range within a river system. Within this system, we also compared the impacts of size specific harvest and uniform harvest across all sizes. We found that targeting the largest, spawning populations may be more important than targeting the populations close to the invasion front for reducing the risk of spreading grass carp. We also demonstrate that size of harvested fish was important for controlling populations.
Pest demography critically determines the viability of synthetic gene drives for population control
11505K. E. Wilkins, T. A. A. Prowse, P. Cassey, P. Q. Thomas and J. V. Ross, Mathematical Biosciences, 305:160-169. 2018-09-13 20:48:39.
Synthetic gene drives offer a novel solution for the control of invasive alien species. CRISPR-based gene drives can positively bias their own inheritance, and comprise a DNA sequence that is replicated by homologous recombination. Since gene drives can be positioned to silence fertility or developmental genes, they could be used for population suppression. However, the production of resistant alleles following self-replication errors threatens the technology's viability for pest eradication in real-world applications. Further, a robust assessment of how pest demography impacts the expected progression of gene drives through populations is currently lacking. We used a deterministic, two-sex, birth-death model to investigate how demographic assumptions affect the efficiency of suppression drives for controlling invasive rodents on islands, for two different gene-drive strategies. We show that mass-action reproduction results in overly optimistic eradication outcomes when compared to the more realistic assumption of polygynous breeding. When polygyny was assumed, both gene-strategies failed due to the evolution of resistance unless a reproductive Allee effect (reduced reproductive rates at low population density) was also included; although model outcomes were highly sensitive to the strength of this effect. Increasing the size of the initial gene-drive introduction (up to 10% of carrying capacity) had little impact on population outcomes. Understanding the demography of a population targeted for eradication is critical before the viability of gene-drive suppression can be adequately assessed.
Sex determination in Neotropical fish: Implications ranging from aquaculture technology to ecological assessment
11495J. I. Fernandino and R. S. Hattori, General and Comparative Endocrinology, 273:172-183. 2018-07-07 20:24:06.
The high biodiversity of fish in the Neotropical region contrasts with scarce or biased studies on the mechanisms involved in the sex determination in members of this fauna. In this review, we attempted to compile the information available on determination, differentiation, and manipulation of sex for Neotropical species, with special focus on silversides and other two speciose groups, known as characins (Characiformes) and catfishes (Siluriformes). Currently, there is plenty of information available on chromosomal sex determination systems, which includes both male and female heterogamety with many variations, and sex chromosomes evolution at the macro chromosomal level. However, there is hitherto a blank in information at micro, gene/molecule levels and in research related to the effects of environmental cues on sex determination; most of reported studies are limited to silversides and guppies. In view of such a high diversity, it is critically necessary to establish key model species for relevant Neotropical fish taxa and also multi-disciplinary research groups in order to uncover the main patterns and trends that dictate the mechanisms of sex determination and gonadal differentiation in this icthyofauna. By increasing our knowledge on sex determination/differentiation with the identification of sex chromosome-linked markers or sex-determining genes, characterization of the onset timing of morphological gonadal differentiation, and determination of the environmental-hormonal labile period of gonadal sex determination in reference species, it will be possible to use those information as guidelines for application in other related groups. Overall, the strategic advance in this research field will be crucial for the development of biotechnological tools for aquaculture industry and for conservation of fish fauna from the Neotropical Region.
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.
Selfish genetic elements
3955Agren, JAC, A. G., PLOS Genetics, 14:20. 2018-01-13 00:00:00.
Selfish genetic elements (historically also referred to as selfish genes, ultra-selfish genes, selfish DNA, parasitic DNA, genomic outlaws) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, even if this has no or a negative effect on organismal fitness. [1-6] Genomes have traditionally been viewed as cohesive units, with genes acting together to improve the fitness of the organism. However, when genes have some control over their own transmission, the rules can change, and so just like all social groups, genomes are vulnerable to selfish behaviour by their parts. Early observations of selfish genetic elements were made almost a century ago, but the topic did not get widespread attention until several decades later. Inspired by the gene-centred views of evolution popularized by George Williams[7] and Richard Dawkins,[8] two papers were published back-to-back in Nature in 1980-by Leslie Orgel and Francis Crick[9] and Ford Doolittle and Carmen Sapienza[10] respectively-introducing the concept of selfish genetic elements (at the time called "selfish DNA") to the wider scientific community. Both papers emphasized that genes can spread in a population regardless of their effect on organismal fitness as long as they have a transmission advantage. Selfish genetic elements have now been described in most groups of organisms, and they demonstrate a remarkable diversity in the ways by which they promote their own transmission.[11] Though long dismissed as genetic curiosities, with little relevance for evolution, they are now recognized to affect a wide swath of biological processes, ranging from genome size and architecture to speciation.[12]
Production of YY Supermale and XY Physiological Female Common Carp for Potential Eradication of this Invasive Species
11508M. Y. Jiang, X. X. Wu, K. X. Chen, H. R. Luo, W. Yu, S. T. Jia, Y. M. Li, Y. F. Wang, P. H. Yang, Z. Y. Zhu and W. Hu, Journal of the World Aquaculture Society, 49:315-327. 2018-01-03 15:22:53.
The common carp, Cyprinus carpio, is the third most cultivated freshwater species worldwide, but is also considered an invasive species. The Trojan Y chromosome strategy is one of the most promising methods to eradicate this invasive species. However, obtaining fertile YY supermale (MYY) and YY physiological female (FYY) common carp was thought to be very difficult. The present study focused on the production of androgenetic MYY and XY physiological female (FXY) common carp. We first optimized the conditions for artificially induced androgenesis. The results indicated that the optimum ultraviolet (UV) exposure time was 4min at an irradiation distance of 26cm and the optimum initiation time with heat shock (40 +/- 0.5C for 2min) was 30min after fertilization. Then, we produced androgenetic MYY Yellow River carp with only paternal inheritance, which were viable and identified by paternity testing and test crossing. Finally, we successfully produced FXY Yellow River carp by feeding 60-d-old MXY with commercially available feed mixed with 17-estradiol (200mg/kg) and Flutamide (200mg/kg) for 3mo. In conclusion, by combining artificially induced androgenesis with an artificially induced sex reversal technique, we could cost-effectively produce MYY and FXY common carp.
Trojan Females and Judas Goats: Evolutionary Traps as Tools in Wildlife Management
13743B. A. Robertson, R. S. Ostfeld and F. Keesing, Bioscience, 67:982-993. 2017-11-01 19:42:43.
Here, we bring together science from the pest-control, eco-evolutionary, and conservation communities to outline how evolutionary traps can be repurposed to eliminate or control pest species. We highlight case studies and devise strategies for the selection of appropriate cues to manipulate, traits to target, and mechanisms to use in setting evolutionary traps that will most rapidly reduce animal abundance while preventing evolutionary escape. We find that evolutionary traps are demonstrably effective and unique tools with high target-species specificity that are deployable in concert with more traditional approaches.
The optimal implementation of the Trojan Y chromosome eradication strategy of invasive species
11510M. R. Kelly and X. Y. Wang, Journal of Biological Systems, 25:399-418. 2017-08-02 15:25:17.
Invasive aquatic species continue to be a persistent problem around the world. The Trojan Y Chromosome (TYC) eradication strategy has recently been developed to help fight the problem in aquatic systems by targeting only the invasive species, sparing native marine stock. It involves rearing genetically modified samples of the invasive species and introducing them into the environment to alter the sex ratio of the invasive population. The paper is devoted to finding the optimal implementation of the TYC eradication strategy of an invasive species as well as a modified, potentially more cost-effective strategy. The modified TYC strategy (MTYC) eliminates one round of exposure to sex hormones compared to the TYC strategy. After introducing both strategies, the optimal control problems for each are formulated. The two strategies are compared through numerical simulations. Our results illustrate that the MTYC strategy, with lower implementation costs, is a better strategy option when trying to minimize the overall effective cost in most scenarios.
Mitonuclear interactions, mtDNA-mediated thermal plasticity, and implications for the Trojan Female Technique for pest control
13745J. N. Wolff, D. M. Tompkins, N. J. Gemmell and D. K. Dowling, Scientific Reports, 6. 2016-07-21 19:45:17.
Here we test whether the male-sterilizing effects previously associated with the mt: Cyt-b mutation are consistent across three thermal and three nuclear genomic contexts. The effects of this mutation were indeed moderated by the nuclear background and thermal environment, but crucially the fertility of males carrying the mutation was invariably reduced relative to controls. This mutation thus constitutes a promising candidate for the further development of the TFT.
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.
Meiotic drive changes sperm precedence patterns in house mice: potential for male alternative mating tactics?
4104Sutter, AL, A. K., BMC Evolutionary Biology, 16:15. 2016-01-02 00:00:00.
Background: With female multiple mating (polyandry), male-male competition extends to after copulation (sperm competition). Males respond to this selective pressure through physiological, morphological and behavioural adaptations. Sperm competitiveness is commonly decreased in heterozygote carriers of male meiotic drivers, selfish genetic elements that manipulate the production of gametes in males. This might give carriers an evolutionary incentive to reduce the risk of sperm competition. Here, we explore this possibility in house mice. Natural populations frequently harbour a well-characterised male driver (t haplotype), which is transmitted to 90 % of heterozygous (+/t) males' offspring. Previous research demonstrated strong detrimental effects on sperm competitiveness, and suggested that +/t males are particularly disadvantaged against wild type males when first-to-mate. Low paternity success in the first-to-mate role is expected to favour male adaptations that decrease the risk of sperm competition by preventing female remating. Genotype-specific paternity patterns (sperm precedence) could lead to genetically determined alternative reproductive tactics that can spread through gene level selection. Here, we seek confirmation that +/t males are generally disadvantaged when first-to-mate and address whether males of different genotypes differ in reproductive tactics (copulatory and morphological) to maximise individual or driver fitness. Finally, we attempt to explain the mechanistic basis for alternative sperm precedence patterns in this species. Results: We confirmed that +/t males are weak sperm competitors when first to mate. When two +/t males competed, the second-to-mate was more successful, which contrasts with first male sperm precedence when wild type males competed. However, we found no differences between male genotypes in reproductive behaviour or morphology that were consistent with alternative reproductive tactics. Sperm of +/+ and +/t males differed with respect to in vitro sperm features. Premature hypermotility in +/t males' sperm can potentially explain why +/t males are very weak sperm competitors when first-to-mate. Conclusions: Our results demonstrate that meiotic drivers can have strong effects on sperm precedence patterns, and may provide a heritable basis for alternative reproductive tactics motivated by reduced sperm competitiveness. We discuss how experimental and evolutionary constraints may help explain why male genotypes did not show the predicted differences.
Production of a YY Male Brook Trout Broodstock for Potential Eradication of Undesired Brook Trout Populations
11516D. J. Schill, J. A. Heindel, M. R. Campbell, K. A. Meyer and E. Mamer, North American Journal of Aquaculture, 78:72-83. 2015-12-31 15:35:45.
Brook Trout Salvelinus fontinalis introduced outside of their native range often negatively impact native aquatic fauna or provide marginal fisheries and are frequently targeted for manual or piscicide removal in lakes and streams. Unfortunately, complete eradication of exotic Brook Trout populations via these methods is rarely achieved; new approaches are needed. A potential alternative is a Trojan Y Chromosome (TYC) program in which hatchery-produced genetically YY male fish would be regularly released into an undesired population over time, skewing the population towards 100% males, theoretically resulting in wild population extirpation. We developed two genetic sex markers for Brook Trout and employed juvenile sex reversal methods commonly used in commercial aquaculture to develop a YY broodstock that can produce offspring for possible future use as biological control agents. Our search for genetic sex markers proved successful, with genotypic sex determination for two assays matching the observed phenotype for 90 out of 90 individuals. In the first phase of the program, estradiol-infused feed readily feminized genetic XY males into neofemales (FXY fish) at a high rate (99.6%; n = 224). Survival of progeny from such egg-laying FXY fish averaged 88% to eye-up and 91% from eye-up to ponding, values similar to untreated Brook Trout reared at the same facility. In the second program phase, we cultured both sperm-and egg-producing supermales (YY fish), a vital step towards development of TYC technology on a large aquaculture scale. Results showed that, in the hatchery, estradiol treatment does not reduce Brook Trout growth. This study demonstrates that hatchery production of a YY Brook Trout broodstock is feasible, modest in cost (less than US$10,000), and can be completed in 4 years. Although several hurdles remain before a full-scale stocking program could occur, we believe that future work on the TYC strategy for Brook Trout is warranted.
Stochastic models for the Trojan Y-Chromosome eradication strategy of an invasive species
11514X. Y. Wang, J. R. Walton and R. D. Parshad, Journal of Biological Dynamics, 10:179-199. 2015-12-16 15:32:37.
The Trojan Y-Chromosome (TYC) strategy, an autocidal genetic bio-control method, has been proposed to eliminate invasive alien species. In this work, we develop a Markov jump process model for this strategy, and we verify that there is a positive probability for wild-type females going extinct within a finite time. Moreover, when sex-reversed Trojan females are introduced at a constant population size, we formulate a stochastic differential equation (SDE) model as an approximation to the proposed Markov jump process model. Using the SDE model, we investigate the probability distribution and expectation of the extinction time of wild-type females by solving Kolmogorov equations associated with these statistics. The results indicate how the probability distribution and expectation of the extinction time are shaped by the initial conditions and the model parameters.
The Trojan Female Technique for pest control: a candidate mitochondrial mutation confers low male fertility across diverse nuclear backgrounds in Drosophila melanogaster
13733D. K. Dowling, D. M. Tompkins and N. J. Gemmell, Evolutionary Applications, 8:8710880. 2015-07-15 19:28:56.
The Trojan Female Technique (TFT) was recently proposed as a prospective approach to biological pest control. However, applicability of the TFT relies on mitochondrial mutations whose male-sterilizing effects are general across nuclear genomic contexts. We test this assumption, expressing the candidate TFT-mutation bearing haplotype alongside a range of nuclear backgrounds and comparing its fertility in males, relative to that of control haplotypes
Ecological and evolutionary applications for environmental sex reversal of fish
11518A. McNair, P. M. Lokman, G. P. Closs and S. Nakagawa, Quarterly Review of Biology, 90:23-44. 2015-03-01 15:38:29.
Environmental sex reversal (ESR), which results in a mismatch between genotypic and phenotypic sex, is well documented in numerous fish species and may be induced by chemical exposure. Historically, research involving piscine ESR has been carried out with a view to improving profitability in aquaculture or to elucidate the processes governing sex determination and sexual differentiation. However, recent studies in evolution and ecology suggest research on ESR now has much wider applications and ramifications. We begin with an overview of ESR in fish and a brief review of the traditional applications thereof We then discuss ESR and its potential demographic consequences in wild populations. Theory even suggests sex-reversed fish may be purposefully released to manipulate population dynamics. We suggest new research directions that may prove fruitful in understanding how ESR at the individual level translates to population-level processes. In the latter portion of the review we focus on evolutionary applications of ESR Sex-reversal studies from the aquaculture literature provide insight in to the evolvability of determinants of sexual phenotype. Additionally, induced sex reversal can provide information about the evolution of sex chromosomes and sex-linked traits. Recently, naturally occurring ESR has been implicated as a mechanism contributing to the evolution of sex chromosomes.
Sperm traits of masculinized fish relative to wild-type males: a systematic review and meta-analyses
11512A. M. Senior, S. L. Johnson and S. Nakagawa, Fish and Fisheries, 17:143-164. 2014-09-11 15:29:18.
Environmental sex reversal (ESR), whereby environmental effects (e.g. exogenous chemicals) override genetic sex determination, is a commonly used technique in aquaculture and physiology research. We performed a systematic review and meta-analyses of the literature that compares the sperm characteristics of masculinized genotypic females to wild-type males. We detected no mean differences between the ejaculate volume, sperm motility, duration or linearity of each type of male. We found some large mean differences in sperm concentration (d=2.541, CI=-0.004 to 5.086), reproductive success (d=-1.400, CI=-2.943 to 0.142), semen osmolality (d=1.850, CI=0.622 to 3.077) and sperm velocity (d=-0.933, CI=-1.426 to -0.441); in the case of the latter two traits, the mean effect was statistically significant. However, any significance did not stand up to a more conservative analysis. Additionally, heterogeneity was high and we found that where large differences between the sperm of sex-reversed and wild-type males are reported, these effects are attributable to sperm sampling methodology. Overall, we found little evidence for large systematic differences between the sperm produced by masculinized and wild-type male fish. Thus, masculinized genotypic females may enjoy reproductive success comparable to genotypic males. This conclusion leads to two potential implications: (i) sex-reversed fish may influence the dynamics of wild populations and (ii) aquaculture practices may use ESR to produce males with sperm quality similar to that of genotypic males. Most studies appear to have been performed in aquaculture species (i.e. Salmonidae); thus future experiments in non-model organisms may provide important insights in to the uniformity of the effects described.
Genetic control of invasive fish: technological options and its role in integrated pest management
4158Thresher, REH, K.; Bax, N. J.; Teem, J.; Benfey, T. J.; Gould, F., Biological Invasions, 16:1201-1216. 2014-01-16 00:00:00.
Genetic options for the control of invasive fishes were recently reviewed and synthesized at a 2010 international symposium, held in Minneapolis/St. Paul, MN, USA. The only option currently available "off-the-shelf'' is triploidy, which can be used to produce sterile males for a release program analogous to those widely and successfully used for biological control of insect pests. However, the Trojan Y and several recombinant options that heritably distort pest population sex ratios are technologically feasible, are at or are close to proof-of-concept stage and are potentially much more effective than sterile male release programs. All genetic options at this stage require prolonged stocking programs to be effective, though gene drive systems are a potential for recombinant approaches. They are also likely to differ in their current degree of social acceptability, with chromosomal approaches (triploidy and Trojan Y) likely to be the most readily acceptable to the public and least likely to require changes in legislative or policy settings to be implemented. Modelling also suggests that the efficacy of any of these genetic techniques is enhanced by, and in turn non-additively enhance, conventional methods of pest fish control.
The Trojan female technique: a novel, effective and humane approach for pest population control
13614N. J. Gemmell, A. Jalilzadeh, R. K. Didham, T. Soboleva and D. M. Tompkins, Proceedings of the Royal Society B: Biological Sciences, 280:20132549. 2013-12-22 13:07:01.
We use mathematical models to test a new twist on the SMT, using maternally inherited mitochondrial (mtDNA) mutations that affect male, but not female reproductive fitness. ‘Trojan females’ carrying suchmutations, and their female descendants, produce ‘sterile-male’-equivalents under natural conditions over multiple generations. We find that the Trojan female technique (TFT) has the potential to be a novel humane approach for pest control.
Global existence and asymptotic behavior of a model for biological control of invasive species via supermale introduction
11530R. D. Parshad, S. Kouachi and J. B. Gutierrez, Communications in Mathematical Sciences, 11:971-992. 2013-06-15 16:00:28.
The purpose of this manuscript is to propose a model for the biological control of invasive species, via introduction of phenotypically modified organisms into a target population. We are inspired by the earlier Trojan Y Chromosome model [J.B. Gutierrez, J.L. Teem, J. Theo. Bio., 241(22), 333-341, 2006]. However, in the current work, we remove the assumption of logistic growth rate, and do not consider the addition of sex-reversed supermales. Also the constant birth and death coefficients, considered earlier, are replaced by functionally dependent ones. In this case the nonlinearities present serious difficulties since they change sign, and the components of the solution are not a priori bounded, in some LP-space for p large, to permit the application of the well known regularizing effect principle. Thus functional methods to deduce the global existence in time, for the system in question, are not applicable. Our techniques are based on the Lyapunov functional method. We prove global existence of solutions, as well as existence of a finite dimensional global attractor, that supports states of extinction. Our analytical finding are in accordance with numerical simulations, which we also present.
Demographic effects on the use of genetic options for the control of mosquitofish, Gambusia holbrooki
11528R. E. Thresher, M. Canning and N. J. Bax, Ecological Applications, 23:801-814. 2013-06-01 15:57:26.
This study tests the sensitivity of genetically based pest control options based on sex ratio distortion to intra-and intersexual aggressive interactions that affect male and female survival and fitness. Data on these interactions and their impacts were gathered for the mosquitofish Gambusia holbrooki (Poeciliidae), a promiscuous species with a strongly male-biased operational sex ratio and well-documented male harassment of females. The experimental design consisted of an orthogonal combination of two population densities and three sex ratios, ranging from strongly male-biased to strongly female-biased, and long-term observations of laboratory populations. Contrary to expectations, the number of males in a population had little evident effect on population demographics. Rather, the density of adult females determined population fecundity (as a result of a stock-recruitment relationship involving females, but not males), constrained male densities (apparently as a result of cannibalism or intersexual aggression), and regulated itself (most likely through effects of intrasexual aggression on female recruitment). The principal effect of males was to constrain their own densities via effects of male-male aggression on adult male mortality rates. Through use of a realistically parameterized genetic/demographic model, we show that of three different genetic options applied to control G. holbrooki, one based on recombinant sex ratio distortion (release of Female Lethal carriers) is marginally more efficient than a sterile male release program, and both outperform an option based on chromosomal sex ratio distortion (Trojan W). Nonlinear dependence of reproductive rate on female density reduces the efficacy of all three approaches. The major effect of intra-and intersexual aggression is mediated through females, whose interactions reduce female numbers and increase the efficacy of a control program based on sex ratio. Socially mediated male mortality has a small impact on control programs due to operational sex ratios that are heavily male-biased. The sensitivity of sex ratio-based control options to social factors will depend on the mating system of the targeted pest, but evidence of widespread density-dependent population regulation suggests that, for most species, the effects of elevated adult mortality (due to intra-and intersexual aggression) on control programs are likely to be slight.
Analysis of the Trojan Y-Chromosome eradication strategy for an invasive species
11524X. Y. Wang, J. R. Walton, R. D. Parshad, K. Storey and M. Boggess, Journal of Mathematical Biology, 68:1731-1756. 2013-05-24 15:52:53.
The Trojan Y-Chromosome (TYC) strategy, an autocidal genetic biocontrol method, has been proposed to eliminate invasive alien species. In this work, we analyze the dynamical system model of the TYC strategy, with the aim of studying the viability of the TYC eradication and control strategy of an invasive species. In particular, because the constant introduction of sex-reversed trojan females for all time is not possible in practice, there arises the question: What happens if this injection is stopped after some time? Can the invasive species recover? To answer that question, we perform a rigorous bifurcation analysis and study the basin of attraction of the recovery state and the extinction state in both the full model and a certain reduced model. In particular, we find a theoretical condition for the eradication strategy to work. Additionally, the consideration of an Allee effect and the possibility of a Turing instability are also studied in this work. Our results show that: (1) with the inclusion of an Allee effect, the number of the invasive females is not required to be very low when the introduction of the sex-reversed trojan females is stopped, and the remaining Trojan Y-Chromosome population is sufficient to induce extinction of the invasive females; (2) incorporating diffusive spatial spread does not produce a Turing instability, which would have suggested that the TYC eradication strategy might be only partially effective, leaving a patchy distribution of the invasive species.
Combining the Trojan Y chromosome and daughterless carp eradication strategies
11522J. L. Teem and J. B. Gutierrez, Biological Invasions, 16:1231-1240. 2013-05-17 15:50:22.
The Trojan Y chromosome (TYC) strategy and the daughterless carp (DC) strategy represent two autocidal genetic biocontrol methods for eliminating invasive fish by changing the sex ratio of the population. Each strategy is designed to reduce the number of females in a target population, ultimately leading to local extinction of the population. In the DC approach, the proportion of males in the population is increased as a result of introducing an autocidal fish containing a transgenic aromatase gene insertion into multiple autosome sites. In the TYC approach, matings of an autocidal fish containing two Y sex chromosomes results in an increased proportion of males in the population. A mathematical model based upon coupled ordinary differential equations was constructed to observe the effect of an autocidal fish with the combined genetic features of both strategies (TYCDC) on a target population. The model incorporated a fitness parameter associated with fish bearing aromatase inhibitor genes and for fish bearing two Y chromosomes. Under conditions where the fitness penalty of the autocidal fish was negligible, modeling results showed that a combined strategy produced a modest reduction in the time required for female eradication, and that fewer autocidal fish were required to achieve extinction. However, increasing the fitness penalty associated with the autocidal fish neutralized the benefits of the TYCDC strategy, and suggested that the effort and expense of a combined strategy may not be warranted if the fitness cost of the TYCDC autocidal fish is significant.
A comparison of the Trojan Y Chromosome and daughterless carp eradication strategies
11520J. L. Teem, J. B. Gutierrez and R. D. Parshad, 16, 16:1217-1230. 2013-05-08 15:46:59.
Two autocidal genetic biocontrol methods have been proposed as a means to eliminate invasive fish by changing the sex ratio of the population: the Trojan Y Chromosome (TYC) strategy and the Daughterless Carp (DC) strategy. Both strategies were modeled using ordinary differential equations that allow the kinetics of female decline to be assessed under identical modeling conditions. When compared directly in an ordinary differential equation (ODE) model, the TYC strategy was found to result in female extinction more rapidly than a DC strategy (in each of three models tested in which the Daughterless autocidal fish contained an aromatase inhibitor gene in either two or eight copies). The TYC strategy additionally required the introduction of fewer autocidal fish to the target population to achieve local extinction of females as compared to the DC approach. The results suggest that the relatively lower efficiency of female reduction associated with the DC approach is a consequence of a greater capacity to produce females and also a reduced capacity to produce males as compared to the TYC system.
A Theoretical Strategy for Eradication of Asian Carps Using a Trojan Y Chromosome to Shift the Sex Ratio of the Population
11538J.L. teem and J.B. Gutierrez, Invasive Asian Carps in North America, 74:227-238. 2011-06-01 17:13:22.
The directed extinction of an exotic fish population is proposed using a genetic approach to drastically reduce the ratio of females to males within the population. In the proposed strategy, sex-reversed female fish containing two Y chromosomes (Fyy) are introduced into a normal fish population. The frequencies of each of the four expected genotypes of fish in the simulated population (Fxx, Fyy, Mxy, and Myy) were modeled with a set of coupled ordinary differential equations. The equations take into account birth rate, death rate, and a fixed carrying capacity of the system. Using computer-generated simulations, it was determined that the continuous introduction of a relatively small proportion of Fyy females to the normal population leads to extinction of the exotic fish over time. The proposed eradication strategy is relevant to fish species with an XY sex-determination system that tolerate a YY genotype. Published literature suggests that Asian carps are likely to fulfill these criteria. However, technical barriers associated with sex reversal in Asian carps presently exist and must be overcome before implementation of a YY eradication strategy for Asian carps can be considered in practice. An idealized theoretical model for the eradication of Asian carps is thus presented.
On the Well Posedness and Refined Estimates for the Global Attractor of the TYC Model
11541R. D. Parshad and J. B. Gutierrez, Boundary Value Problems, 2010-11-22 17:23:35.
The Trojan Y Chromosome strategy (TYC) is a theoretical method for eradication of invasive species. It requires constant introduction of artificial individuals into a target population, causing a shift in the sex ratio that ultimately leads to local extinction. In this work we demonstrate the existence of a unique weak solution to the infinite dimensional TYC system. Furthermore, we obtain improved estimates on the upper bounds for the Hausdorff and fractal dimensions of the global attractor of the TYC system, via the use of weighted Sobolev spaces. These results confirm that the TYC eradication strategy is a sound theoretical method of eradication of invasive species in a spatial setting. It also provides a solid ground for experiments in silico and validates the use of the TYC strategy in vivo.
On the global attractor of the Trojan Y chromosome model.
11536R. D. Parshad and J. B. Gutierrez, Communications on Pure and Applied Analysis, 10:339-359. 2010-01-01 17:11:02.
We consider the Trojan Y Chromosome (TYC) model for eradication of invasive species in population dynamics. We present global estimates for the TYC system in a spatial domain. In this work we prove the existence of a global attractor for the system. We derive uniform estimates to tackle the question of asymptotic compactness of the semi-group for the TYC model in H(2)(Omega). This along with the existence of a bounded absorbing set, which we also derive, demonstrates the existence of a global attractor for the TYC model. The present analysis reveals that extinction of an invasive species is always possible to achieve irrespective of geometric considerations of the domain. This result is valid for TYC systems in which advection is negligible. This theoretical work lays the foundation for experimental studies of the application of the TYC eradication strategy in spatial ecology, since the outcome is in principle guaranteed.
Control of introduced species using Trojan sex chromosomes
11543S. Cotton and C. Wedekind, Trends in Ecology & Evolution, 22:441-443. 2007-07-20 17:25:46.
To control introduced exotic species that have predominantly genetic, but environmentally reversible, sex determination (e.g. many species of fish), Gutierrez and Teem recently modeled the use of carriers of Trojan Y chromosomes - individuals who are phenotypically sex reversed from their genotype. Repeated introduction of YY females into wild populations should produce extreme male-biased sex ratios and eventual elimination of XX females, thus leading to population extinction. Analogous dynamics are expected in systems in which sex determination is influenced by one or a few major genes on autosomes.
A model describing the effect of sex-reversed YY fish in an established wild population: The use of a Trojan Y chromosome to cause extinction of an introduced exotic species
11545J. B. Gutierrez and J. L. Teem, Journal of Theoretical Biology, 241:333-341. 2006-01-06 17:28:07.
A novel means of inducing extinction of an exotic fish population is proposed using a genetic approach to shift the ratio of male to females within a population. In the proposed strategy, sex-reversed fish containing two Y chromosomes are introduced into a normal fish population. These YY fish result in the production of a disproportionate number of male fish in subsequent generations. Mathematical modeling of the system following introduction of YY fish at a constant rate reveals that female fish decline in numbers over time, leading to eventual extinction of the population. (c) 2005 Elsevier Ltd. All rights reserved.
B chromosomes and genome size in flowering plants
4301Trivers, RB, A.; Palestis, B. G., Genome, 47:1-8. 2004-01-19 00:00:00.
B chromosomes are extra chromosomes found in some, but not all, individuals within a species, often maintained by giving themselves an advantage in transmission, i.e. they drive. Here we show that the presence of B chromosomes correlates to and varies strongly and positively with total genome size (excluding the Bs and corrected for ploidy) both at a global level and via a comparison of independent taxonomic contrasts. B chromosomes are largely absent from species with small genomes; however, species with large genomes are studied more frequently than species with small genomes and Bs are more likely to be reported in well-studied species. We controlled for intensity of study using logistic regression. This regression analysis also included effects of degree of outbreeding, which is positively associated with Bs and genome size, and chromosome number, which is negatively associated with Bs and genome size, as well as variable ploidy (more than one ploidy level in a species). Genome size, breeding system and chromosome number all contribute independently to the distribution of B chromosomes, while variable ploidy does not have a significant effect. The genome size correlates are consistent with reduced selection against extra DNA in species with large genomes and with increased generation of B sequences from large A genomes.

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