Scholarly Literature
This is an aggregation of scholarly literature from peer-reviewed journals, bioRxiv , medRxiv and arXiv preprint servers focused on natural and engineered selfish genetic elements and genetic biocontrol. New citations are added as they appear. This content is intended for anyone interested in the scholarly literature on gene drive and genetic biocontrol.
Preferential accumulation of sex and Bs chromosomes in biarmed karyotypes by meiotic drive and rates of chromosomal changes in fishes
4147Molina, WFM, P. A.; Bertollo, L. A. C.; Bidau, C. J., Anais Da Academia Brasileira De Ciencias, 86:1801-1812. 2014-01-05 00:00:00.
Mechanisms of accumulation based on typical centromeric drive or of chromosomes carrying pericentric inversions are adjusted to the general karyotype differentiation in the principal Actinopterygii orders. Here, we show that meiotic drive in fish is also supported by preferential establishment of sex chromosome systems and B chromosomes in orders with predominantly bi-brachial chromosomes. The mosaic of trends acting at an infra-familiar level in fish could be explained as the interaction of the directional process of meiotic drive as background, modulated on a smaller scale by adaptive factors or specific karyotypic properties of each group, as proposed for the orthoselection model.
Medusa: A novel gene drive system for confined suppression of insect populations
4146Marshall, JMH, B. A., PLOS One, 9:e102694. 2014-01-04 00:00:00.
Gene drive systems provide novel opportunities for insect population suppression by driving genes that confer a fitness cost into pest or disease vector populations; however regulatory issues arise when genes are capable of spreading across international borders. Gene drive systems displaying threshold properties provide a solution since they can be confined to local populations and eliminated through dilution with wild-types. We propose a novel, threshold-dependent gene drive system, Medusa, capable of inducing a local and reversible population crash. Medusa consists of four components - two on the X chromosome, and two on the Y chromosome. A maternally-expressed, X-linked toxin and a zygotically-expressed, Y-linked antidote results in suppression of the female population and selection for the presence of the transgene-bearing Y because only male offspring of Medusa-bearing females are protected from the effects of the toxin. At the same time, the combination of a zygotically-expressed, Y-linked toxin and a zygotically-expressed, X-linked antidote selects for the transgene-bearing X in the presence of the transgene-bearing Y. Together these chromosomes create a balanced lethal system that spreads while selecting against females when present above a certain threshold frequency. Simple population dynamic models show that an all-male release of Medusa males, carried out over six generations, is expected to induce a population crash within 12 generations for modest release sizes on the order of the wild population size. Re-invasion of non-transgenic insects into a suppressed population can result in a population rebound; however this can be prevented through regular releases of modest numbers of Medusa males. Finally, we outline how Medusa could be engineered with currently available molecular tools.
The organization and evolution of the Responder satellite in species of the Drosophila melanogaster group: dynamic evolution of a target of meiotic drive
4145Larracuente, AM, BMC Evolutionary Biology, 14:233. 2014-01-03 00:00:00.
: Satellite DNA can make up a substantial fraction of eukaryotic genomes and has roles in genome structure and chromosome segregation. The rapid evolution of satellite DNA can contribute to genomic instability and genetic incompatibilities between species. Despite its ubiquity and its contribution to genome evolution, we currently know little about the dynamics of satellite DNA evolution. The Responder (Rsp) satellite DNA family is found in the pericentric heterochromatin of chromosome 2 of Drosophila melanogaster. Rsp is well-known for being the target of Segregation Distorter (SD) an autosomal meiotic drive system in D. melanogaster. I present an evolutionary genetic analysis of the Rsp family of repeats in D. melanogaster and its closely-related species in the melanogaster group (D. simulans, D. sechellia, D. mauritiana, D. erecta, and D. yakuba) using a combination of available BAC sequences, whole genome shotgun Sanger reads, Illumina short read deep sequencing, and fluorescence in situ hybridization. Results: I show that Rsp repeats have euchromatic locations throughout the D. melanogaster genome, that Rsp arrays show evidence for concerted evolution, and that Rsp repeats exist outside of D. melanogaster, in the melanogaster group. The repeats in these species are considerably diverged at the sequence level compared to D. melanogaster, and have a strikingly different genomic distribution, even between closely-related sister taxa. Conclusions: The genomic organization of the Rsp repeat in the D. melanogaster genome is complex it exists of large blocks of tandem repeats in the heterochromatin and small blocks of tandem repeats in the euchromatin. My discovery of heterochromatic Rsp-like sequences outside of D. melanogaster suggests that SD evolved after its target satellite and that the evolution of the Rsp satellite family is highly dynamic over a short evolutionary time scale (<240,000 years).
Evolution and biology of supernumerary B chromosomes
4144Houben, AB-M, A. M.; Klemme, S.; Timmis, J. N., Cellular and Molecular Life Sciences, 71:467-478. 2014-01-02 00:00:00.
B chromosomes (Bs) are dispensable components of the genome exhibiting non-Mendelian inheritance and have been widely reported on over several thousand eukaryotes, but still remain an evolutionary mystery ever since their first discovery over a century ago [1]. Recent advances in genome analysis have significantly improved our knowledge on the origin and composition of Bs in the last few years. In contrast to the prevalent view that Bs do not harbor genes, recent analysis revealed that Bs of sequenced species are rich in gene-derived sequences. We summarize the latest findings on supernumerary chromosomes with a special focus on the origin, DNA composition, and the non-Mendelian accumulation mechanism of Bs.
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.
Swarming and mating behavior of male Anopheles arabiensis Patton (Diptera: Culicidae) in an area of the Sterile Insect Technique Project in Dongola, northern Sudan
25815M. M. Hassan, H. M. Zain, M. A. Basheer, H. E. F. Elhaj and B. B. El-Sayed, Acta Tropica, 132:S64-S69. 2013-11-27 08:57:21.
The problems facing the conventional mosquito control methods including resistance to insecticides have led to the development of alternative methods such as the Sterile Insect Technique (SIT) to suppress populations of the malaria vector Anopheles arabiensis in northern Sudan. This method entails the release of large numbers of irradiated males to compete against wild conspecifics for mating with virgin females in the field. The swarming and mating behaviors of this species were conducted at two field sites during the period 2009-2012 in Dongola, northern Sudan. Observations were made in the field sites and in a contained semi-field enclosure. In addition, participation of released irradiated-marked males in the swarms of wild mosquito was investigated. Swarms were observed on sunset in the vicinity of larval habitats around irrigation channel and stopped with the onset of the darkness about 21-25 min after the start. Swarms were observed above visual markers such as palm trees, bare ground, and manure. Several couples were observed leaving the swarms in copula in the direction of the sunlight. The majority of copulations were observed within 12-15 min of the start of swarming. Relatively low insemination rates (28%) of females collected from coupling pairs were observed. Irradiated-marked males were observed to join the natural swarms regularly, indicating their probable competitiveness with the other wild males. These findings enhance the feasibility of staging an SIT campaign against malaria vector in Northern State-Sudan. Copyright (C) International Atomic Energy Agency 2013. Published by Elsevier B.V. All rights reserved.
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.
Elimination of Y chromosome-bearing spermatids during spermiogenesis in an autosomal sex-ratio mutant of Drosophila simulans
4183Yasuno, YI, Y. H.; Yamamoto, M. T., Genes & Genetic Systems, 88:113-126. 2013-01-21 00:00:00.
Sex ratio distortion, which is commonly abbreviated as sex-ratio, has been studied in many Drosophila species, but the mechanism remains largely unknown. Here, we report on the sex-ratio mutant of D. simulans named excess of females (exf). The third chromosomal recessive mutation results in a sex ratio of approximately 0.2 or less (males/total). Cytological observation demonstrated that meiosis appeared to be completed normally, but that most Y chromosome-bearing nuclei failed to elongate during spermiogenesis, as revealed by fluorescence in situ hybridization using sex chromosome-specific probes. These aberrant nuclei contained membranous inclusions as revealed by electron microscopic analysis. Most of the aberrant exf spermatids failed to individualize and mature, suggesting that a later stage of spermiogenesis is involved in prevention of production of sperm with abnormal morphology. On the one hand, in exf seminal vesicles, sperm nuclei with a length of 5-8.5 mu m were occasionally observed, in addition to those with wild-type sperm dimensions, that is, a length of approximately 10 mu m. Thus, spermatids with less severe nuclear defects can escape elimination and be released into the seminal vesicles as mature sperm. Furthermore, we constructed His2AvD-GFP and ProtamineB-eGFP transgenic lines in D. simulans, and examined the processes involved in replacement of chromatin proteins over a time course, according to nuclear morphology. We found that both normal and abnormal sperm heads demonstrated equal chromatin replacement during late spermiogenesis. Our results suggest that exf belongs to a unique class of meiotic drive systems in that (1) intranuclear membranous inclusions cause failure of nuclear shaping of Y-bearing spermatids without affecting the histone-protamine transition, and (2) a portion of the aberrant spermatids differentiate into mature sperm; these are transferred to and stored by females.
Engineering synthetic medea-based and threshold- dependent underdominance-based gene drive systems in mosquitoes
4163Akbari, OM, J.; Antoshechkin, I.; Matzen, K.; Papathanos, P.; Kennedy, K.; Ward, C.; Chen, C. H.; Guo, M.; Hay, B., Pathogens and Global Health, 107:442-442. 2013-01-21 00:00:00.
Mosquito population replacement requires gene drive mechanisms in order to spread linked genes, mediating disease refractoriness, through wild populations. Medea is predicted to be a low threshold gene drive mechanism, able to spread from low initial frequency. Such a system is ideal when the goal is area-wide population replacement. However, once released, it is difficult to restore the pre-transgenic state, if desired. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread provide an attractive alternative because they bring about local, but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal- effect lethal underdominance (UDMEL). We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. We will describe the dynamics of the UDMEL system, and our progress in transferring Medea and UDMEL into Aedes aegypti.
Sex-biased gene expression during head development in a sexually dimorphic stalk-eyed fly
4182Wilkinson, GSJ, P. M.; Metheny, J. D.; Baker, R. H., PLOS One, 8:1-10. 2013-01-20 00:00:00.
Stalk-eyed flies (family Diopsidae) are a model system for studying sexual selection due to the elongated and sexually dimorphic eye-stalks found in many species. These flies are of additional interest because their X chromosome is derived largely from an autosomal arm in other flies. To identify candidate genes required for development of dimorphic eyestalks and investigate how sex-biased expression arose on the novel X, we compared gene expression between males and females using oligonucleotide microarrays and RNA from developing eyestalk tissue or adult heads in the dimorphic diopsid, Teleopsis dalmanni. Microarray analysis revealed sex-biased expression for 26% of 3,748 genes expressed in eye-antennal imaginal discs and concordant sex-biased expression for 86 genes in adult heads. Overall, 415 female-biased and 482 male-biased genes were associated with dimorphic eyestalk development but not differential expression in the adult head. Functional analysis revealed that male-biased genes are disproportionately associated with growth and mitochondrial function while female-biased genes are associated with cell differentiation and patterning or are novel transcripts. With regard to chromosomal effects, dosage compensation occurs by elevated expression of X-linked genes in males. Genes with female-biased expression were more common on the X and less common on autosomes than expected, while male-biased genes exhibited no chromosomal pattern. Rates of protein evolution were lower for female-biased genes but higher for genes that moved on or off the novel X chromosome. These findings cannot be due to meiotic sex chromosome inactivation or by constraints associated with dosage compensation. Instead, they could be consistent with sexual conflict in which female-biased genes on the novel X act primarily to reduce eyespan in females while other genes increase eyespan in both sexes. Additional information on sex-biased gene expression in other tissues and related sexually monomorphic species could confirm this interpretation.
The dynamic relationship between polyandry and selfish genetic elements
4181Wedell, N, Philosophical Transactions of the Royal Society B-Biological Sciences, 368:10. 2013-01-19 00:00:00.
Selfish genetic elements (SGEs) are ubiquitous in eukaryotes and bacteria, and make up a large part of the genome. They frequently target sperm to increase their transmission success, but these manipulations are often associated with reduced male fertility. Low fertility of SGE-carrying males is suggested to promote polyandry as a female strategy to bias paternity against male carriers. Support for this hypothesis is found in several taxa, where SGE-carrying males have reduced sperm competitive ability. In contrast, when SGEs give rise to reproductive incompatibilities between SGE-carrying males and females, polyandry is not necessarily favoured, irrespective of the detrimental impact on male fertility. This is due to the frequency-dependent nature of these incompatibilities, because they will decrease in the population as the frequency of SGEs increases. However, reduced fertility of SGE-carrying males can prevent the successful population invasion of SGEs. In addition, SGEs can directly influence male and female mating behaviour, mating rates and reproductive traits (e. g. female reproductive tract length and male sperm). This reveals a potent and dynamic interaction between SGEs and polyandry highlighting the potential to generate sexual selection and conflict, but also indicates that polyandry can promote harmony within the genome by undermining the spread of SGEs.
Meiotic drive in mice carrying t-complex in their genome
4180Safronova, LDC, V. L., Russian Journal of Genetics, 49:885-897. 2013-01-18 00:00:00.
The deviation of alleles and chromosomes from Mendelian inheritance is characteristic of the meiotic drive. This review describes the mechanism in question using the best-studied example of transmitted ratio distortion in the heterozygous male mice carrying t-haplotypes. The t-complex is best model for studying the meiotic drive under laboratory conditions. Putative mechanisms of meiotic drive that influence the frequency of t-haplotypes in natural populations are considered, of which prezygotic selection is the most important. The role of meiotic drive in male hybrid sterility is emphasized. The factors and models that determine the phenomenon of meiotic drive are discussed in detail.
Association of polyandry and sex-ratio drive prevalence in natural populations of Drosophila neotestacea
4179Pinzone, CAD, K. A., Proceedings of the Royal Society B-Biological Sciences, 280:20131397. 2013-01-17 00:00:00.
Selfish genetic elements bias their own transmission to the next generation, even at the expense of the fitness of their carrier. Sex-ratio (SR) meiotic drive occurs when an X-chromosome causes Y-bearing sperm to die during male spermatogenesis, so that it is passed on to all of the male's offspring, which are all daughters. How SR is maintained as a stable polymorphism in the absence of genetic suppressors of drive is unknown. Here, we investigate the potential for the female remating rate to affect SR dynamics in natural populations, using the fly Drosophila neotestacea. In controlled laboratory conditions, females from populations where SR is rare mate more often than females from populations where SR is common. Furthermore, only when males mate multiply does the average fertility of SR males relative to wild-type males decrease to a level that can prevent SR from spreading. Our results suggest that differences in the female mating rate among populations may contribute to SR dynamics in the wild, and thus also affect the outcome of this intragenomic conflict. In line with this, we also present evidence of a localized population crash due to SR that may have resulted from habitat fragmentation along with a reduced mating rate.
Transmission rate variation among three B chromosome variants in the fish Prochilodus lineatus (Characiformes, Prochilodontidae)
4178Penitente, MV, T. A.; Senhorini, J. A.; Bortolozzi, J.; Foresti, F.; Porto-Foresti, F., Anais Da Academia Brasileira De Ciencias, 85:1371-1377. 2013-01-16 00:00:00.
Cytogenetic studies were developed in Prochilodus lineatus (Valenciennes 1836), describing an interesting system of small supernumerary chromosomes. The purpose of this work is to study the frequency and morphology of B chromosomes in individuals from the parental line and the inheritance patterns of these elements in individuals obtained from controlled crosses in the species P. lineatus. The transmission rate of B chromosomes, revealed a k(B)=0.388 for the acrocentric type, a kB=0.507 for the metacentric type and a k(B)=0.526 for the submetacentric type. The obtained results raise hypothesis that B-acrocentric chromosomes are involved in an extinction process in this species, while the metacentric and submetacentric supernumerary elements comprises a neutral mechanism and follows a Mendelian transmission rate.
Modelling the spatial spread of a homing endonuclease gene in a mosquito population
4177North, AB, A.; Godfray, H. C. J., Journal of Applied Ecology, 50:1216-1225. 2013-01-15 00:00:00.
Homing endonuclease genes (HEGs) exist naturally in many single-celled organisms and can show extremely strong genetic drive allowing them to spread through populations into which they are introduced. They are being investigated as tools to manipulate the populations of important vectors of human disease, in particular the mosquitoes that transmit malaria. Before HEGs can be deployed, it is important to study their spatial spread in order to design efficient release strategies. A spatially explicit model is developed to study the spread of a HEG through a landscape whose structure is defined by the distribution of mosquito breeding and feeding sites. The model is motivated by the biology of the major vectors of malaria in Africa. The conditions for spread, fixation and loss of two major types of HEG are explored in different landscapes. In landscapes where mosquito resources are abundant, the conditions for spread are well approximated by a mean-field model. Where a HEG imposes a genetic load, it can cause population extinction, though spatial models more often predict population suppression. In certain types of landscapes where mosquito resources are rare, an introduced HEG may be prevented from moving between local mosquito populations and so a simple release strategy is unlikely to be effective, yet if the HEG succeeds in spreading population extinction is a feasible outcome. Increasing the number of release sites at the expense of releasing fewer mosquitoes per site reduces the probability that a HEG will fail.Synthesis and applications. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study. The model presented asks for the first time how the spatial structure of mosquito populations will influence the effectiveness of a technology that is being rapidly developed for vector control. If homing endonuclease genes (HEGs) are to be used in this way, we have qualified the importance of accounting for landscape characteristics in both the execution and the expectation of their application. The next stage is to use the model to study the spread of HEGs through real landscapes where releases may take place, something that will be facilitated by the results of the present study.
Spread of a new parasitic B chromosome variant is facilitated by high gene flow
4176Manrique-Poyato, MIL-L, M. D.; Cabrero, J.; Perfectti, F.; Camacho, J. P. M., PLOS One, 8:e83712. 2013-01-14 00:00:00.
The B-24 chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B-24 frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise N(e)m estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B-24 diffusion both eastward and westward, with minor role for B-24 drive due to the arrival of drive suppressor genes which are also frequent in the donor population.
Modeling the dynamics of a non-limited and a self-limited gene drive system in structured Aedes aegypti populations
4175Legros, MX, C. G.; Morrison, A.; Scott, T. W.; Lloyd, A. L.; Gould, F., PLOS One, 8:e83354. 2013-01-13 00:00:00.
Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local vector populations. Because of the potential of these selfish elements to spread through populations, control approaches based on these strategies must be carefully evaluated to ensure a balance between the desirable spread of the refractoriness-conferring genetic cargo and the avoidance of potentially unwanted outcomes such as spread to non-target populations. There is also a need to develop better estimates of the economics of such releases. We present here an evaluation of two such strategies using a biologically realistic mathematical model that simulates the resident Aedes aegypti mosquito population of Iquitos, Peru. One strategy uses the selfish element Medea, a non-limited element that could permanently spread over a large geographic area; the other strategy relies on Killer-Rescue genetic constructs, and has been predicted to have limited spatial and temporal spread. We simulate various operational approaches for deploying these genetic strategies, and quantify the optimal number of released transgenic mosquitoes needed to achieve definitive spread of Medea-linked genes and/or high frequencies of Killer-Rescue-associated elements. We show that for both strategies the most efficient approach for achieving spread of anti-pathogen genes within three years is generally to release adults of both sexes in multiple releases over time. Even though females in these releases should not transmit disease, there could be public concern over such releases, making the less efficient male-only release more practical. This study provides guidelines for operational approaches to population replacement genetic strategies, as well as illustrates the use of detailed spatial models to assist in safe and efficient implementation of such novel genetic strategies.
Diversity and abundance of the abnormal chromosome 10 meiotic drive complex in Zea mays
4174Kanizay, LBP, T.; Lowry, E. G.; Hufford, M. B.; Peterson, D. G.; Ross-Ibarra, J.; Dawe, R. K., Heredity, 110:570-577. 2013-01-12 00:00:00.
Maize Abnormal chromosome 10 (Ab10) contains a classic meiotic drive system that exploits the asymmetry of meiosis to preferentially transmit itself and other chromosomes containing specialized heterochromatic regions called knobs. The structure and diversity of the Ab10 meiotic drive haplotype is poorly understood. We developed a bacterial artificial chromosome (BAC) library from an Ab10 line and used the data to develop sequence-based markers, focusing on the proximal portion of the haplotype that shows partial homology to normal chromosome 10. These molecular and additional cytological data demonstrate that two previously identified Ab10 variants (Ab10-I and Ab10-II) share a common origin. Dominant PCR markers were used with fluorescence in situ hybridization to assay 160 diverse teosinte and maize landrace populations from across the Americas, resulting in the identification of a previously unknown but prevalent form of Ab10 (Ab10-III). We find that Ab10 occurs in at least 75% of teosinte populations at a mean frequency of 15%. Ab10 was also found in 13% of the maize landraces, but does not appear to be fixed in any wild or cultivated population. Quantitative analyses suggest that the abundance and distribution of Ab10 is governed by a complex combination of intrinsic fitness effects as well as extrinsic environmental variability.
Transmission ratio distortion: review of concept and implications for genetic association studies
4173Huang, LOL, A.; Infante-Rivard, C., Human Genetics, 132:245-263. 2013-01-11 00:00:00.
Transmission ratio distortion (TRD) occurs when one of the two alleles from either parent is preferentially transmitted to the offspring. This leads to a statistical departure from the Mendelian law of inheritance, which states that each of the two parental alleles is transmitted to offspring with a probability of 0.5. A number of mechanisms are thought to induce TRD such as meiotic drive, gametic competition, and embryo lethality. TRD has been extensively studied in animals, but the prevalence of TRD in humans remains largely unknown. Nevertheless, understanding the TRD phenomenon and taking it into consideration in many aspects of human genetics has potential benefits that have not been sufficiently emphasized in the current literature. In this review, we discuss the importance of TRD in three distinct but related fields of genetics: developmental genetics which studies the genetic abnormalities in zygotic and embryonic development, statistical genetics/genetic epidemiology which utilizes population study designs and statistical models to interpret the role of genes in human health, and population genetics which is concerned with genetic diversity in populations in an evolutionary context. From the perspective of developmental genetics, studying TRD leads to the identification of the processes and mechanisms for differential survival observed in embryos. As a result, it is a genetic force which affects allele frequency at the population, as well as, at the organismal level. Therefore, it has implications on genetic diversity of the population over time. From the perspective of genetic epidemiology, the TRD influence on a marker locus is a confounding factor which has to be adequately dealt with to correctly interpret linkage or association study results. These aspects are developed in this review. In addition to these theoretical notions, a brief summary of the empirical evidence of the TRD phenomenon in human and mouse studies is provided. The objective of our paper is to show the potentially important role of TRD in many areas of genetics, and to create an incentive for future research.
Mutations to the piRNA Pathway Component Aubergine Enhance Meiotic Drive of Segregation Distorter in Drosophila melanogaster
4172Gell, SLR, R. A., Genetics, 193:771-784. 2013-01-10 00:00:00.
Diploid sexual reproduction involves segregation of allelic pairs, ensuring equal representation of genotypes in the gamete pool. Some genes, however, are able to "cheat" the system by promoting their own transmission. The Segregation distorter (Sd) locus in Drosophila melanogaster males is one of the best-studied examples of this type of phenomenon. In this system the presence of Sd on one copy of chromosome 2 results in dysfunction of the non-Sd-bearing (Sd(+)) sperm and almost exclusive transmission of Sd to the next generation. The mechanism by which Sd wreaks such selective havoc has remained elusive. However, its effect requires a target locus on chromosome 2 known as Responder (Rsp). The Rsp locus comprises repeated copies of a satellite DNA sequence and Rsp copy number correlates with sensitivity to Sd. Under distorting conditions during spermatogenesis, nuclei with chromosomes containing greater than several hundred Rsp repeats fail to condense chromatin and are eliminated. Recently, Rsp sequences were found as small RNAs in association with Argonaute family proteins Aubergine (Aub) and Argonaute3 (AGO3). These proteins are involved in a germ-line-specific RNAi mechanism known as the Piwi-interacting RNA (piRNA) pathway, which specifically suppresses transposon activation in the germline. Here, we evaluate the role of piRNAs in segregation distortion by testing the effects of mutations to piRNA pathway components on distortion. Further, we specifically targeted mutations to the aub locus of a Segregation Distorter (SD) chromosome, using ends-out homologous recombination. The data herein demonstrate that mutations to piRNA pathway components act as enhancers of SD.
Guidance on the environmental risk assessment of genetically modified animals.
4171EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms), EFSA Journal, 11:3200. 2013-01-09 00:00:00.
This document provides guidance for the environmental risk assessment (ERA) of living genetically modified (GM) animals, namely fish, insects and mammals and birds, to be placed on the European Union (EU) market in accordance with Regulation (EC) No 1829/2003 or Directive 2001/18/EC. It provides guidance for assessing potential effects of GM animals on animal and human health and the environment and the rationales for data requirements for a comprehensive ERA. The ERA should be carried out on a case-by-case basis, following a step-by-step assessment approach. This document describes the six sequential steps for the ERA of GM animals, as indicated in Directive 2001/18/EC: (1) problem formulation including hazard and exposure identification; (2) hazard characterisation; (3) exposure characterisation; (4) risk characterisation; (5) risk management strategies; and (6) an overall risk evaluation. The Scientific Panel on Genetically Modified Organisms of the European Food Safety Authority follows Annex II of Directive 2001/18/EC, considering specific areas of risk to be addressed by applicants and risk assessors during the ERA of GM fish, GM insects and GM mammals and birds. Each specific area of risk is considered in a structured and systematic way following the aforementioned six steps. In addition, this Guidance Document describes several generic cross-cutting considerations (e.g. choice of comparators, use of non-GM surrogates, experimental design and statistics, long-term effects, uncertainty analysis) that need to be accounted for throughout the whole ERA.
Mechanism of meiotic drive in mammals
4170Chmatal, LF, K.; Schultz, R. M.; Lampson, M. A., Molecular Biology of the Cell, 24:3775. 2013-01-08 00:00:00.
Meiotic drive is a phenomenon responsible for an unequal representation of alleles or whole chromosomes among gametes as a result of the mechanics of meiotic division (Sandler et Novitski 1957). When it drives segregation of Robertsonian translocations (Rb), a common chromosomal rearrangement in mammals, in oocytes these translocations are either preferentially maintained in the egg or preferentially expelled to the polar body during meiosis I (MI), thus being either transmitted or excluded from the next generation. Because Rb translocations are formed by fusion of two acrocentric chromosomes creating one metacentric chromosome, subsequent accumulation and fixation of these fusions over time leads to a change in karyotype (Castaglia 1982, Villena et Sapienza 2001). Despite the importance of this phenomenon for evolution and speciation, the underlying mechanisms of meiotic drive are unknown. We tested a model of meiotic drive based on three elements: (1) an asymmetric trivalent that forms in MI when a metacentric fusion pairs with the two homologous acrocentric chromosomes, (2) preferential orientation of the trivalent on an asymmetric spindle, and (3) orientation of the asymmetric spindle with one side preferentially facing the cortex. We find reduced levels of kinetochore proteins in fusion centromeres compared to the homologous acrocentric centromeres, suggesting that the trivalent asymmetry is based on differential centromere strength. We also find that stability of MI spindle microtubules is influenced by proximity to the cortex, leading to asymmetric spindles with more stable microtubules oriented towards the cortex. These MTs preferentially bind the fusion centromere, which orients the metacentric Rb fusion chromosome towards the cortex for eventual segregation to the polar body.Together, our data provide evidence for a model to explain the biased segregation of Rb translocations in mammalian oocytes.
The design and in vivo evaluation of engineered I-OnuI-based enzymes for HEG gene drive
4169Chan, YST, R.; Jarjour, J.; Huen, D. S.; Stoddard, B. L.; Russell, S., PLOS One, 8:e74254. 2013-01-07 00:00:00.
The homing endonuclease gene (HEG) drive system, a promising genetic approach for controlling arthropod populations, utilises engineered nucleases to spread deleterious mutations that inactivate individual genes throughout a target population. Previous work with a naturally occurring LAGLIDADG homing endonuclease (I-SceI) demonstrated its feasibility in both Drosophila and Anopheles. Here we report on the next stage of this strategy: the redesign of HEGs with customized specificity in order to drive HEG-induced 'homing' in vivo via break-induced homologous recombination. Variants targeting a sequence within the Anopheles AGAP004734 gene were created from the recently characterized I-OnuI endonuclease, and tested for cleavage activity and frequency of homing using a model Drosophila HEG drive system. We observed cleavage and homing at an integrated reporter for all endonuclease variants tested, demonstrating for the first time that engineered HEGs can cleave their target site in insect germline cells, promoting targeted mutagenesis and homing. However, in comparison to our previously reported work with I-SceI, the engineered I-OnuI variants mediated homing with a reduced frequency, suggesting that site-specific cleavage activity is insufficient by itself to ensure efficient homing. Taken together, our experiments take a further step towards the development of a viable HEG-based population control strategy for insects.
Optimising homing endonuclease gene drive performance in a semi-refractory species: The Drosophila melanogaster experience
4168Chan, YSH, D. S.; Glauert, R.; Whiteway, E.; Russell, S., PLOS One, 8:e54130. 2013-01-06 00:00:00.
Homing endonuclease gene (HEG) drive is a promising insect population control technique that employs meganucleases to impair the fitness of pest populations. Our previous studies showed that HEG drive was more difficult to achieve in Drosophila melanogaster than Anopheles gambiae and we therefore investigated ways of improving homing performance in Drosophila. We show that homing in Drosophila responds to increased expression of HEGs specifically during the spermatogonia stage and this could be achieved through improved construct design. We found that 39-UTR choice was important to maximise expression levels, with HEG activity increasing as we employed Hsp70, SV40, vasa and beta Tub56D derived UTRs. We also searched for spermatogonium-specific promoters and found that the Rcd-1r promoter was able to drive specific expression at this stage. Since Rcd-1 is a regulator of differentiation in other species, it suggests that Rcd-1r may serve a similar role during spermatogonial differentiation in Drosophila. Contrary to expectations, a fragment containing the entire region between the TBPH gene and the bgcn translational start drove strong HEG expression only during late spermatogenesis rather than in the germline stem cells and spermatogonia as expected. We also observed that the fraction of targets undergoing homing was temperature-sensitive, falling nearly four-fold when the temperature was lowered to 18 degrees C. Taken together, this study demonstrates how a few simple measures can lead to substantial improvements in the HEG-based gene drive strategy and reinforce the idea that the HEG approach may be widely applicable to a variety of insect control programs.
Natural variation of the Y chromosome suppresses sex ratio distortion and modulates testis-specific gene expression in Drosophila simulans
4167Branco, ATT, Y.; Hartl, D. L.; Lemos, B., Heredity, 111:8-15. 2013-01-05 00:00:00.
X-linked sex-ratio distorters that disrupt spermatogenesis can cause a deficiency in functional Y-bearing sperm and a female-biased sex ratio. Y-linked modifiers that restore a normal sex ratio might be abundant and favored when a X-linked distorter is present. Here we investigated natural variation of Y-linked suppressors of sex-ratio in the Winters systems and the ability of these chromosomes to modulate gene expression in Drosophila simulans. Seventy-eight Y chromosomes of worldwide origin were assayed for their resistance to the X-linked sex-ratio distorter gene Dox. Y chromosome diversity caused males to sire similar to 63% to similar to 98% female progeny. Genome-wide gene expression analysis revealed hundreds of genes differentially expressed between isogenic males with sensitive (high sex ratio) and resistant (low sex ratio) Y chromosomes from the same population. Although the expression of about 75% of all testis-specific genes remained unchanged across Y chromosomes, a subset of post-meiotic genes was upregulated by resistant Y chromosomes. Conversely, a set of accessory gland-specific genes and mitochondrial genes were downregulated in males with resistant Y chromosomes. The D. simulans Y chromosome also modulated gene expression in XXY females in which the Y-linked protein-coding genes are not transcribed. The data suggest that the Y chromosome might exert its regulatory functions through epigenetic mechanisms that do not require the expression of protein-coding genes. The gene network that modulates sex ratio distortion by the Y chromosome is poorly understood, other than that it might include interactions with mitochondria and enriched for genes expressed in post-meiotic stages of spermatogenesis.
Local dynamics of a fast-evolving sex-ratio system in Drosophila simulans
4166Bastide, HG, P. R.; Ogereau, D.; Cazemajor, M.; Montchamp-Moreau, C., Molecular Ecology, 22:5352-5367. 2013-01-04 00:00:00.
By distorting Mendelian transmission to their own advantage, X-linked meiotic drive elements can rapidly spread in natural populations, generating a sex-ratio bias. One expected consequence is the triggering of a co-evolutionary arms race between the sex chromosome that carries the distorter and suppressors counteracting its effect. Such an arms race has been theoretically and experimentally established and can have many evolutionary consequences. However, its dynamics in contemporary populations is still poorly documented. Here, we investigate the fate of the young X-linked Paris driver in Drosophila simulans from sub-Saharan Africa to the Middle East. We provide the first example of the early dynamics of distorters and suppressors: we find consistent evidence that the driving chromosomes have been rising in the Middle East during the last decade. In addition, identical haplotypes are at high frequencies around the two co-evolving drive loci in remote populations, implying that the driving X chromosomes share a recent common ancestor and suggesting that East Africa could be the cradle of the Paris driver. The segmental duplication associated with drive presents an unusual structure in West Africa, which could reflect a secondary state of the driver. Together with our previous demonstration of driver decline in the Indian Ocean where suppression is complete, these data provide a unique picture of the complex dynamics of a co-evolutionary arms race currently taking place in natural populations of D.simulans.
Germline excision of transgenes in Aedes aegypti by homing endonucleases
4165Aryan, AA, M. A. E.; Myles, K. M.; Adelman, Z. N., Scientific Reports, 3:1603. 2013-01-03 00:00:00.
Aedes (Ae.) aegypti is the primary vector for dengue viruses (serotypes1-4) and chikungunya virus. Homing endonucleases (HEs) are ancient selfish elements that catalyze double-stranded DNA breaks (DSB) in a highly specific manner. In this report, we show that the HEs Y2-I-AniI, I-CreI and I-SceI are all capable of catalyzing the excision of genomic segments from the Ae. aegypti genome in a heritable manner. Y2-I-AniI demonstrated the highest efficiency at two independent genomic targets, with 20-40% of Y2-I-AniI-treated individuals producing offspring that had lost the target transgene. HE-induced DSBs were found to be repaired via the single-strand annealing (SSA) and non-homologous end-joining (NHEJ) pathways in a manner dependent on the availability of direct repeat sequences in the transgene. These results support the development of HE-based gene editing and gene drive strategies in Ae. aegypti, and confirm the utility of HEs in the manipulation and modification of transgenes in this important vector.
A Synthetic Gene Drive System for Local, Reversible Modification and Suppression of Insect Populations
4164Akbari, OSM, K. D.; Marshall, J. M.; Huang, H. X.; Ward, C. M.; Hay, B. A., Current Biology, 23:671-677. 2013-01-02 00:00:00.
Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a self-perpetuating method of disease prevention but requires a gene drive mechanism to spread these traits to high frequency [1-3]. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread are attractive because they bring about local but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals [4-6]. These features are likely to be important in many social and regulatory contexts [7-10]. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal-effect lethal underdominance (UDMEL), in which two maternally expressed toxins, located on separate chromosomes, are each linked with a zygotic antidote able to rescue maternal-effect lethality of the other toxin. We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. Models suggest that transgene spread can often be limited to local environments. They also show that in a population in which single-locus UDMEL has been carried out, repeated release of wild-type males can result in population suppression, a novel method of genetic population manipulation.
Ethical issues in field trials of genetically modified disease-resistant mosquitoes
13538D. B. Resnik, Developing World Bioethics, 14:37-46. 2012-07-29 19:12:07.
Mosquito-borne diseases take a tremendous toll on human populations, especially in developing nations. In the last decade, scientists have developed mosquitoes that have been genetically modified to prevent transmission of mosquito-borne diseases, and field trials have been conducted. Some mosquitoes have been rendered infertile, some have been equipped with a vaccine they transmit to humans, and some have been designed to resist diseases.
The contribution of female meiotic drive to the evolution of neo-sex chromosomes
4197Yoshida, KK, J., Evolution, 66:3198-3208. 2012-01-15 00:00:00.
Sex chromosomes undergo rapid turnover in certain taxonomic groups. One of the mechanisms of sex chromosome turnover involves fusions between sex chromosomes and autosomes. Sexual antagonism, heterozygote advantage, and genetic drift have been proposed as the drivers for the fixation of this evolutionary event. However, all empirical patterns of the prevalence of multiple sex chromosome systems across different taxa cannot be simply explained by these three mechanisms. In this study, we propose that female meiotic drive may contribute to the evolution of neo-sex chromosomes. The results of this study showed that in mammals, the XY1Y2 sex chromosome system is more prevalent in species with karyotypes of more biarmed chromosomes, whereas the X1X2Y sex chromosome system is more prevalent in species with predominantly acrocentric chromosomes. In species where biarmed chromosomes are favored by female meiotic drive, X-autosome fusions (XY1Y2 sex chromosome system) will be also favored by female meiotic drive. In contrast, in species with more acrocentric chromosomes, Y-autosome fusions (X1X2Y sex chromosome system) will be favored just because of the biased mutation rate toward chromosomal fusions. Further consideration should be given to female meiotic drive as a mechanism in the fixation of neo-sex chromosomes.
From genes to games: Cooperation and cyclic dominance in meiotic drive
4196Traulsen, AR, F. A., Journal of Theoretical Biology, 299:120-125. 2012-01-14 00:00:00.
Evolutionary change can be described on a genotypic level or a phenotypic level. Evolutionary game theory is typically thought of as a phenotypic approach, although it is frequently argued that it can also be used to describe population genetic evolution. Interpreting the interaction between alleles in a diploid genome as a two player game leads to interesting alternative perspectives on genetic evolution. Here we focus on the case of meiotic drive and illustrate how meiotic drive can be directly and precisely interpreted as a social dilemma, such as the prisoners dilemma or the snowdrift game, in which the drive allele takes more than its fair share. Resistance to meiotic drive can lead to the well understood cyclic dominance found in the rock-paper-scissors game. This perspective is well established for the replicator dynamics, but there is still considerable ground for mutual inspiration between the two fields. For example, evolutionary game theorists can benefit from considering the stochastic evolutionary dynamics arising from finite population size. Population geneticists can benefit from game theoretic tools and perspectives on genetic evolution. (c) 2011 Elsevier Ltd. All rights reserved.
Genetic mapping a meiotic driver that causes sex ratio distortion in the mosquito Aedes aegypti
4195Shin, DM, A.; Severson, D. W., Journal of Heredity, 103:303-307. 2012-01-13 00:00:00.
An endogenous meiotic driver in the dengue and yellow fever vector mosquito Aedes aegypti can cause highly male-biased sex ratio distortion in crosses from suitable genetic backgrounds. We previously selected a strain that carries a strong meiotic drive gene (D) linked with the maledetermining allele (M) on chromosome 1 in A. aegypti. Here, we performed segregation analysis of the M-D locus among backcross (BC1) progeny from a driver male and drive- sensitive females. Assessment of sex ratios among BC2 progeny showed; similar to 5.2% recombination between the M-D locus and the sex determination locus. Multipoint linkage mapping across this region revealed consistent marker orders and recombination frequencies with the existing reference linkage map and placed the M-D locus within a 6.5-cm interval defined by the LF159 locus and microsatellite marker 446GAA, which should facilitate future positional cloning efforts.
No evidence of mate discrimination against males carrying a sex ratio distorter in Drosophila pseudoobscura
4194Price, TARL, Z.; Smith, D. T.; Hurst, G. D. D.; Wedell, N., Behavioral Ecology and Sociobiology, 66:561-568. 2012-01-12 00:00:00.
Selfish genetic elements (SGEs) that spread by manipulating spermatogenesis often have highly deleterious effects on males that carry them. Females that mate with male carriers of SGEs can also suffer significant costs: they receive fewer and poorer-quality sperm, their offspring will inherit the deleterious allele, and the sex ratio of their offspring will be biased towards the more common sex. To counter these costs, females are therefore expected to prefer to mate with males that do not carry sex ratio distorters or other deleterious selfish genetic elements. However, despite the potential costs, there are few examples of female choice against males carrying SGEs. We searched for evidence of a female preference in fruit fly Drosophila pseudoobscura against males carrying a costly meiotic driving X-chromosome Sex Ratio (SR). In a series of five non-competitive mate preference experiments, we find no evidence that females prefer to mate with non-SR males. Our use of five separate experiments, involving more than 800 females, makes it unlikely that this lack of a difference was due to low power or simple chance. We suggest that the lack of female choice against SGE-carrying males may be due to strong selection on SGEs to be indistinguishable from alternative alleles. Furthermore, polyandry, either in direct response to receiving an ejaculate from an SGE-carrying male or carried out indiscriminately when at risk of mating with carriers, may be an alternative response by females to limit the exposure of their offspring to SGEs.
Evaluating the evidence for transmission distortion in human pedigrees
4193Meyer, WKA, B.; Ober, C.; Ebner, T.; Tiemann-Boege, I.; Hudson, R. R.; Przeworski, M., Genetics, 191:215-232. 2012-01-11 00:00:00.
Children of a heterozygous parent are expected to carry either allele with equal probability. Exceptions can occur, however, due to meiotic drive, competition among gametes, or viability selection, which we collectively term "transmission distortion" (TD). Although there are several well-characterized examples of these phenomena, their existence in humans remains unknown. We therefore performed a genome-wide scan for TD by applying the transmission disequilibrium test (TDT) genome-wide to three large sets of human pedigrees of European descent: the Framingham Heart Study (FHS), a founder population of European origin (HUTT), and a subset of the Autism Genetic Resource Exchange (AGRE). Genotyping error is an important confounder in this type of analysis. In FHS and HUTT, despite extensive quality control, we did not find sufficient evidence to exclude genotyping error in the strongest signals. In AGRE, however, many signals extended across multiple SNPs, a pattern highly unlikely to arise from genotyping error. We identified several candidate regions in this data set, notably a locus in 10q26.13 displaying a genome-wide significant TDT in combined female and male transmissions and a signature of recent positive selection, as well as a paternal TD signal in 6p21.1, the same region in which a significant TD signal was previously observed in 30 European males. Neither region replicated in FHS, however, and the paternal signal was not visible in sperm competition assays or as allelic imbalance in sperm. In maternal transmissions, we detected no strong signals near centromeres or telomeres, the regions predicted to be most susceptible to female-specific meiotic drive, but we found a significant enrichment of top signals among genes involved in cell junctions. These results illustrate both the potential benefits and the challenges of using the TDT to study transmission distortion and provide candidates for investigation in future studies.
Confinement of gene drive systems to local populations: A comparative analysis
4192Marshall, JMH, B. A., Journal of Theoretical Biology, 294:153-171. 2012-01-10 00:00:00.
Mosquito-borne diseases such as malaria and dengue fever pose a major health problem through much of the world. One approach to disease prevention involves the use of selfish genetic elements to drive disease-refractory genes into wild mosquito populations. Recently engineered synthetic drive systems have provided encouragement for this strategy; but at the same time have been greeted with caution over the concern that transgenes may spread into countries and communities without: their consent. Consequently, there is also interest in gene drive systems that, while strong enough to bring about local population replacement, are unable to establish themselves beyond a partially isolated release site, at least during the testing phase. Here, we develop simple deterministic and stochastic models to compare the confinement properties of a variety of gene drive systems. Our results highlight several systems with desirable features for confinement-a high migration rate required to become established in neighboring populations, and low-frequency persistence in neighboring populations for moderate migration rates. Single-allele underdominance and single-locus engineered underdominance have the strongest confinement properties, but are difficult to engineer and require a high introduction frequency, respectively. Toxin-antidote systems such as Semele. Merea and two-locus engineered underdominance show promising confinement properties and require lower introduction frequencies. Killer-rescue is self-limiting in time, but is able to disperse to significant levels in neighboring populations. We discuss the significance of these results in the context of a phased release of transgenic mosquitoes, and the need for characterization of local ecology prior to a release. (C) 2011 Elsevier Ltd. All rights reserved.
General principles of single-construct chromosomal gene drive
4191Marshall, JMH, B. A., Evolution, 66:2150-2166. 2012-01-09 00:00:00.
Gene drive systems are genetic elements capable of spreading into a population even if they confer a fitness cost to their host. We consider a class of drive systems consisting of a chromosomally located, linked cluster of genes, the presence of which renders specific classes of offspring arising from specific parental crosses unviable. Under permissive conditions, a number of these elements are capable of distorting the offspring ratio in their favor. We use a population genetic framework to derive conditions under which these elements spread to fixation in a population or induce a population crash. Many of these systems can be engineered using combinations of toxin and antidote genes, analogous to Medea, which consists of a maternal toxin and zygotic antidote. The majority of toxinantidote drive systems require a critical frequency to be exceeded before they spread into a population. Of particular interest, a Z-linked Medea construct with a recessive antidote is expected to induce an all-male population crash for release frequencies above 50%. We suggest molecular tools that may be used to build these systems, and discuss their relevance to the control of a variety of insect pest species, including mosquito vectors of diseases such as malaria and dengue fever.
The Selfish Segregation Distorter Gene Complex of Drosophila melanogaster
4190Larracuente, AMP, D. C., Genetics, 192:33-53. 2012-01-08 00:00:00.
Segregation Distorter (SD) is an autosomal meiotic drive gene complex found worldwide in natural populations of Drosophila melanogaster. During spermatogenesis, SD induces dysfunction of SD+ spermatids so that SD/SD+ males sire almost exclusively SD-bearing progeny rather than the expected 1:1 Mendelian ratio. SD is thus evolutionarily "selfish," enhancing its own transmission at the expense of its bearers. Here we review the molecular and evolutionary genetics of SD. Genetic analyses show that the SD is a multilocus gene complex involving two key loci-the driver, Segregation distorter (Sd), and the target of drive, Responder (Rsp)-and at least three upward modifiers of distortion. Molecular analyses show that Sd encodes a truncated duplication of the gene RanGAP, whereas Rsp is a large pericentromeric block of satellite DNA. The Sd-RanGAP protein is enzymatically wild type but mislocalized within cells and, for reasons that remain unclear, appears to disrupt the histone-to-protamine transition in drive-sensitive spermatids bearing many Rsp satellite repeats but not drive-insensitive spermatids bearing few or no Rsp satellite repeats. Evolutionary analyses show that the Sd-RanGAP duplication arose recently within the D. melanogaster lineage, exploiting the preexisting and considerably older Rsp satellite locus. Once established, the SD haplotype collected enhancers of distortion and suppressors of recombination. Further dissection of the molecular genetic and cellular basis of SD-mediated distortion seems likely to provide insights into several important areas currently understudied, including the genetic control of spermatogenesis, the maintenance and evolution of satellite DNAs, the possible roles of small interfering RNAs in the germline, and the molecular population genetics of the interaction of genetic linkage and natural selection.
Complex genetic nature of sex-independent transmission ratio distortion in Asian rice species: the involvement of unlinked modifiers and sex-specific mechanisms
4189Koide, YS, Y.; Ikenaga, M.; Sawamura, N.; Matsubara, K.; Onishi, K.; Kanazawa, A.; Sano, Y., Heredity, 108:242-247. 2012-01-07 00:00:00.
Transmission ratio distortion (TRD), in which one allele is transmitted more frequently than the opposite allele, is presumed to act as a driving force in the emergence of a reproductive barrier. TRD acting in a sex-specific manner has been frequently observed in interspecific and intraspecific hybrids across a broad range of organisms. In contrast, sex-independent TRD (SITRD), which results from preferential transmission of one of the two alleles in the heterozygote through both sexes, has been detected in only a few plant species. We previously reported an S-6 locus-mediated SITRD, in which the S-6 allele from an Asian wild rice strain (Oryza rufipogon) was transmitted more frequently than the S-6(a) allele from an Asian cultivated rice strain (O. sativa) through both male and female gametes in heterozygous plants. Here, we report on the effect of a difference in genetic background on S-6 locus-mediated SITRD, based on the analysis using near-isogenic lines and the original wild strain as a parental strain for crossing. We found that the degree of TRD through the male gametes varied depending on the genetic background of the female (pistil) plants. Despite the occurrence of TRD through both male and female gametes, abnormality was detected in ovules, but not in pollen grains, in the heterozygote. These results suggest the involvement of unlinked modifiers and developmentally distinct, sex-specific genetic mechanisms in S-6 locus-mediated SITRD, raising the possibility that SITRD driven by a single locus may be affected by multiple genetic factors harbored in natural populations. Heredity (2012) 108, 242-247; doi:10.1038/hdy.2011.64; published online 27 July 2011
B chromosomes in plants
4188Jones, N, Plant Biosystems, 146:727-737. 2012-01-06 00:00:00.
B chromosomes (Bs) can be described as "selfish chromosomes", a term that has been used for the repetitive DNA which comprises the bulk of the genome in large genome species, except that Bs have a life of their own as independent chromosomes. They can accumulate in number by various processes of mitotic or meiotic drive, especially in the gametophyte phase of the life cycle of flowering plants. This parasitic property of drive ensures their survival and spread in natural populations, even against a gradient of harmful effects on the host plant phenotype. B chromosomes are inhabitants of the nucleus and they are subject to control by "genes" in the A chromosome (As) complement. This interaction with the As, together with the balance between drive and harmful effects makes a dynamic system in the life of a Bs. In this review, we concentrate mainly on recent developments in the Bs of rye and maize, two of the species currently receiving most attention. We focus on their population dynamics and on the molecular basis of their structural organisation and mechanisms of drive, as well as on their mode of origin and potential applications in plant biotechnology.
Molecular dissection of Neurospora Spore killer meiotic drive elements
4187Hammond, TMR, D. G.; Xiao, H.; Shiu, P. K. T., Proceedings of the National Academy of Sciences of the United States of America, 109:12093-12098. 2012-01-05 00:00:00.
Meiotic drive is a non-Mendelian inheritance phenomenon in which certain selfish genetic elements skew sexual transmission in their own favor. In some cases, progeny or gametes carrying a meiotic drive element can survive preferentially because it causes the death or malfunctioning of those that do not carry it. In Neurospora, meiotic drive can be observed in fungal spore killing. In a cross of Spore killer (Sk) x WT (Sk-sensitive), the ascospores containing the Spore killer allele survive, whereas the ones with the sensitive allele degenerate. Sk-2 and Sk-3 are the most studied meiotic drive elements in Neurospora, and they each theoretically contain two essential components: a killer element and a resistance gene. Here we report the identification and characterization of the Sk resistance gene, rsk (resistant to Spore killer). rsk seems to be a fungal-specific gene, and its deletion in a killer strain leads to self-killing. Sk-2, Sk-3, and naturally resistant isolates all use rsk for resistance. In each killer system, rsk sequences from an Sk strain and a resistant isolate are highly similar, suggesting that they share the same origin. Sk-2, Sk-3, and sensitive rsk alleles differ from each other by their unique indel patterns. Contrary to long-held belief, the killer targets not only late but also early ascospore development. The WT RSK protein is dispensable for ascospore production and is not a target of the spore-killing mechanism. Rather, a resistant version of RSK likely neutralizes the killer element and prevents it from interfering with ascospore development.
Local selection underlies the geographic distribution of sex-ratio drive in Drosophila neotestacea
4186Dyer, KA, Evolution, 66:973-984. 2012-01-04 00:00:00.
Selfish genetic elements promote their own transmission to the next generation, often at a cost to the host individual. A sex-ratio (SR) driving X chromosome prevents the maturation of Y-bearing sperm, and as a result is transmitted to 100% of the offspring, all of which are female. Because the spread of a SR chromosome can result in a female-biased population sex ratio, the ecological and evolutionary consequences of harboring this selfish element can be severe. In this study, we show that the prevalence of SR drive in Drosophila neotestacea varies between 0% and 30% among populations, and is common in the south whereas rare in the north. The prevalence of SR is not associated with the presence of suppressors of drive, geographic distance, or genetic distance based on autosomal microsatellite loci. Instead, our results indicate that ecological selection on SR drive varies among populations, as the prevalence of SR is highly correlated with climatic factors, with the severity of winter the best determinant of SR frequency. Thus, ecological and demographic factors may have significant consequences for the short and long term evolutionary dynamics of selfish elements and the manner with which they coevolve with the rest of the genome.
Scrambling eggs: Meiotic drive and the evolution of female recombination rates
4185Brandvain, YC, G., Genetics, 190:709-723. 2012-01-03 00:00:00.
Theories to explain the prevalence of sex and recombination have long been a central theme of evolutionary biology. Yet despite decades of attention dedicated to the evolution of sex and recombination, the widespread pattern of sex differences in the recombination rate is not well understood and has received relatively little theoretical attention. Here, we argue that female meiotic drivers-alleles that increase in frequency by exploiting the asymmetric cell division of oogenesis-present a potent selective pressure favoring the modification of the female recombination rate. Because recombination plays a central role in shaping patterns of variation within and among dyads, modifiers of the female recombination rate can function as potent suppressors or enhancers of female meiotic drive. We show that when female recombination modifiers are unlinked to female drivers, recombination modifiers that suppress harmful female drive can spread. By contrast, a recombination modifier tightly linked to a driver can increase in frequency by enhancing female drive. Our results predict that rapidly evolving female recombination rates, particularly around centromeres, should be a common outcome of meiotic drive. We discuss how selection to modify the efficacy of meiotic drive may contribute to commonly observed patterns of sex differences in recombination.
Nondisjunction in favor of a Chromosome: The mechanism of rye B chromosome drive during pollen mitosis
4184Banaei-Moghaddam, AMS, V.; Kumke, K.; Weiss, O.; Klemme, S.; Nagaki, K.; Macas, J.; Gonzalez-Sanchez, M.; Heredia, V.; Gomez-Revilla, D.; Gonzalez-Garcia, M.; Vega, J. M.; Puertas, M. J.; Houben, A., Plant Cell, 24:4124-4134. 2012-01-02 00:00:00.
B chromosomes (Bs) are supernumerary components of the genome and do not confer any advantages on the organisms that harbor them. The maintenance of Bs in natural populations is possible by their transmission at higher than Mendelian frequencies. Although drive is the key for understanding B chromosomes, the mechanism is largely unknown. We provide direct insights into the cellular mechanism of B chromosome drive in the male gametophyte of rye (Secale cereale). We found that nondisjunction of Bs is accompanied by centromere activity and is likely caused by extended cohesion of the B sister chromatids. The B centromere originated from an A centromere, which accumulated B-specific repeats and rearrangements. Because of unequal spindle formation at the first pollen mitosis, nondisjoined B chromatids preferentially become located toward the generative pole. The failure to resolve pericentromeric cohesion is under the control of the B-specific nondisjunction control region. Hence, a combination of nondisjunction and unequal spindle formation at first pollen mitosis results in the accumulation of Bs in the generative nucleus and therefore ensures their transmission at a higher than expected rate to the next generation.
Evaluating the potential of the sterile insect technique for malaria control: relative fitness and mating compatibility between laboratory colonized and a wild population of Anopheles arabiensis from the Kruger National Park, South Africa
25909G. Munhenga, B. D. Brooke, T. F. Chirwa, R. H. Hunt, M. Coetzee, D. Govender and L. L. Koekemoer, Parasites and Vectors, 4:208. 2011-10-31 12:48:58.
The successful suppression of a target insect population using the sterile insect technique (SIT) partly depends on the premise that the laboratory insects used for mass rearing are genetically compatible with the target population, that the mating competitiveness of laboratory reared males is at least comparable to that of their wild counterparts, and that mass rearing and sterilization processes do not in themselves compromise male fitness to a degree that precludes them from successfully competing for mates in the wild. This study investigated the fitness and sexual cross-compatibility between samples of field collected and laboratory reared An. arabiensis under laboratory conditions.
Field performance of engineered male mosquitoes
6401A. F. Harris, D. Nimmo, A. R. McKemey, N. Kelly, S. Scaife, C. A. Donnelly, C. Beech, W. D. Petrie and L. Alphey, Nature Biotechnology, 29:1034-1037. 2011-10-30 16:54:55.
Mass-release of sterile male mosquitoes is a promising option for controlling dengue and malaria, but it has never been shown that lab-raised transgenic males can compete effectively with their wild counterparts outside laboratory conditions. Promising results from a restricted field trail now suggest the feasibility of extending the approach for large-scale mosquito-control programs.
An integrated campaign against riverine tsetse, Glossina palpalis gambiensis and Glossina tachinoides by trapping, and the release of sterile males
An integrated campaign against riverine tsetse, Glossina palpalis gambiensis and Glossina tachinoides by trapping, and the release of sterile males, International Journal of Tropical Insect Science, 5:439-442. 2011-09-19 15:29:15.The combination of a trapping system of insecticide impregnated screens and biconical traps followed by the release of sterile males led to the complete control of Glossina palpalis gambiensis and Glossina tachinoides in the agro-pastoral zone of Sideradougou. This area, situated south of Bobo Dioulasso, Upper Volta, in the Guinea savannah, covers an area of approx. 3000 km2. Along more than 650 km of rivers, bordered by gallery forests and infested by riverine tsetse, 6500 impregnated screens were placed during 4 months of the dry season, followed by the release of sterile males in the rainy season. For release purposes, colonies of 150,000 producing females of G.p. gambiensis and 85,000 females of G. tachinoides were maintained in industrial colonies on artificial membranes. Reinvasion of the project area was prevented by two barriers consisting of biconical traps impregnated with synthetic pyrethroid in one and simple biconical capture traps in the other. The screens reduced the initial fly population by 94% and permitted the release of only 35 sterile males per km of river to attain the planned ratio of seven sterile males to one wild male. Regular surveys showed that, after 4 months of release of sterile males, the relic fly population was constantly decreasing and tending towards disappearance.An economic evaluation based on the production costs of the sterile males together with the costs of field operations showed that this combination of two non-pollutant methods was competitive with other methods of tsetse control.
