Keywords: Y-chromosome
Signatures of sex ratio distortion in humans
35441James Guy Baldwin-Brown, Sergiusz Wesolowski, Raquel Mae Reisinger, et al., bioRxiv, 2026-02-10 18:42:47.
Segregation distortion, the disproportionate inheritance of selfish genetic elements, is an important evolutionary force. While many species carry distorters, it is not clear if humans do. Major limitations for detecting human distortion are the small size of human families and the lack of genetic markers in most subjects. Here, we present evidence of strong distortion in a large human pedigree. We analyzed pedigrees from the Utah Population Database and identified lineages with a high chance of carrying a distorter. In particular, we identified a family that preferentially produced male offspring at a 2:1 ratio. This pattern is consistent with a distorting Y-chromosome, a rarity in species with degenerate Y-chromosomes. The detection of such non-Mendelian inheritance patterns suggests that human genomes may harbor segregation distorters.
D. melanogaster meiotic driver Stellate compromises sperm development by impeding a process of nuclear envelope remodeling
35390Xuefeng Meng, Yukiko M Yamashita,, Genetics, 2026-01-23 09:55:19.
Meiotic drive is a phenomenon that violates Mendel’s Law of Equal Segregation, leading to biased transmission of the meiotic driver to the offspring. D. melanogaster Stellate (Ste) is an X-linked meiotic driver that preferentially harms Y-chromosome-bearing spermatids, thereby favoring the transmission of the X chromosome to the next generation. We have recently shown that Ste protein segregates asymmetrically during meiosis I with a strong bias toward the Y-chromosome-inheriting side, leading to the eventual demise of the Y-chromosome-containing spermatids. However, the cellular mechanisms by which Ste protein interferes with spermatid development remain unknown. Here, we show that Ste-containing spermatids are delayed in the process of nuclear envelope remodeling, an essential process during sperm DNA compaction. We show that components of the nuclear lamina (such as Lamin Dm0, and the LEM domain proteins Otefin and Bocks) are rapidly removed during nuclear envelope remodeling during the early stages of normal spermatid development. However, Ste-containing spermatids retained these nuclear lamina proteins for a prolonged time. Their delayed removal is associated with defective formation of the dense complex, which is composed of a bundle of microtubules and serves as a structural support for sperm nuclear morphogenesis. Defective dense complex formation in Ste-containing spermatids led to defective sperm DNA compaction. Together, the present study reveals an unexpected cellular mechanism by which a meiotic driver, Ste, sabotages sperm development.
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 Stellate meiotic drive system of Drosophila melanogaster is active in contemporary populations
35215Benjamin K McCormick, Daniel A Barbash, Andrew G Clark, bioRxiv, 2025-10-05 12:58:27.
Meiotic drivers are selfish elements that bias their own transmission so that they are overrepresented among the functional gametes produced. The selective costs imposed by drivers on their hosts may trigger intragenomic conflict, promoting the evolution of suppressors and fueling an ongoing arms race between drivers and suppressors. Stellate (Ste) is an X-linked tandemly arrayed multicopy gene. Its copy number ranges from 3 to more than 300 among Drosophila melanogaster strains from the Global Diversity Lines. In wild-type animals, Ste expression is usually suppressed by homologous piRNAs produced from the Suppressor of Stellate (Su(Ste)) array on the Y chromosome. Derepression of Ste in the absence Su(Ste) results in the formation of proteinaceous crystals in spermatocytes, chromatin compaction defects, reductions in fertility, and female-biased sex ratios arising from under-recovery of Y-bearing sperm. Despite extensive study, the function of the Stellate array and evolutionary significance of its persistence in the genome have remained elusive. It has been suggested to be a now-inactive relic of an ancient meiotic drive system, as perturbations in lab stocks can produce Ste-mediated meiotic distortions. Meiotic drive occurring among natural variants, however, has not been reported. We established crosses between females with high Ste copy number X chromosomes and males carrying low Su(Ste) copy number Y chromosomes and found that the male progeny displayed non-Mendelian sex chromosome transmission. Importantly, deletion of the euSte array in an otherwise matched genetic background rescues this phenotype, demonstrating that Stellate is an active driver in contemporary populations.
D. melanogaster meiotic driver Stellate compromises sperm development by impeding nuclear envelope remodeling
35211Xuefeng M Meng, Yukiko M Yamashita, bioRxiv, 2025-10-02 15:00:55.
Meiotic drive is a phenomenon that violates Mendels Law of Equal Segregation, leading to biased transmission of the meiotic driver to the offspring. D. melanogaster Stellate (Ste) is an X-linked meiotic driver that preferentially harms Y-chromosome-bearing spermatids, thereby favoring the transmission of the X chromosome to the next generation. We have recently shown that Ste protein segregates asymmetrically during meiosis I with a strong bias toward the Y-chromosome-inheriting side, leading to the eventual demise of the Y-chromosome-containing spermatids. However, the cellular mechanisms by which Ste protein interferes with spermatid development remain unknown. Here, we show that Ste-containing spermatids are delayed in the process of nuclear envelope remodeling, an essential process during sperm DNA compaction. We show that Lamin Dm0, a component of the nuclear lamina, is rapidly removed during nuclear envelope remodeling during the early stages of normal spermatid development. However, Ste-containing spermatid retained Lamin Dm0 for a prolonged time. Delayed Lamin Dm0 removal is associated with defective formation of the dense complex, which is composed of the bundle of microtubules and serves as a structural support for sperm nuclear morphogenesis. Defective dense complex formation in Ste-containing spermatid led to defective sperm DNA compaction. Together, the present study reveals an unexpected cellular mechanism by which a meiotic driver, Ste, sabotages sperm development.
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.
Natural Selection of Synthetic Gene Drives for Population Suppression Can Favor an Intermediate Strength of Drive
35141P. J. Beaghton and Austin Burt, The American Naturalist, 206. 2025-09-16 15:55:03.
Synthetic gene drives are being investigated as tools to suppress pest populations, and it is important to understand how natural selection will act on variant drivers that may either arise by de novo mutation or be intentionally released. In this study, we extend previous spatially implicit stochastic models to examine the evolutionary dynamics of synthetic driving Y chromosomes in patchy environments when population size is responding dynamically to the spread of the driver and derive conditions for the existence of an evolutionarily stable strategy (ESS) for drive strength. Under broad conditions, an intermediate drive strength emerges as the ESS, capable of outcompeting both stronger and weaker variants. Additionally, we show how the intentional release of two drivers straddling the ESS can help stabilize population dynamics. Finally, inbreeding depression has the effect of expanding the range of conditions under which no intermediate ESS exists, with ever stronger drive being selected until the population is eliminated. These results provide insights into the expected evolutionary trajectories of gene drive systems, with important implications for the design and release of gene drives for pest and vector control.
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.
Suppression of sex-ratio drive in Drosophila subobscura
35233Sophie Lyth, Tom Gill, Andri Manser, et al., Evolution, 2025-07-30 15:46:21.
Selfish genetic elements enjoy an evolutionary advantage by enhancing their own transmission to offspring, and their genetic suppressors are favored when they re-establish fair inheritance patterns. Here, we study an X-linked sex ratio drive system (SR) in Drosophila subobscura, which kills Y-bearing sperm of SR males, resulting in the over-transmission of the SR chromosome and a strong female bias in their offspring. We surveyed D. subobscura populations in North Africa, which naturally harbor SR, and found that suppression occurs in ∼13.5% of wild-derived lines. We characterize this suppression phenotype through a series of crossing experiments, including multigenerational introgression of SR chromosomes into a suppressing genetic background. We show that introgression can restore normal offspring sex ratios or, in some cases, result in an excess of male offspring. This suppression appears to be a multilocus trait, involving autosomes and the Y chromosomes. Suppression of SR fails to ameliorate all costs of drive, with fully suppressed SR-carrying males having depressed fertility and low offspring egg hatch rates. Further examination of internal male reproductive organs using microscopy suggests that suppressed SR males also have abnormal testes. These factors may explain why the suppression fails to reach high frequencies, despite the strong advantage of suppressing SR.
Reenacting a mouse genetic evolutionary arms race in yeast reveals that SLXL1/SLX compete with SLY1/2 for binding to Spindlins
34550M.F. Arlt,A.N. Kruger,C.M. Swanepoel,& J.L. Mueller, Proceedings of the National Academy of Sciences, 122. 2025-03-04 10:54:14.
In the house mouse, an evolutionary arms race between proteins encoded by the X-linked Slxl1/Slx and Y-linked Sly gene families during spermatogenesis can distort offspring sex ratio, but how these proteins compete remains unknown. We report how SLXL1/SLX competes with SLY1/SLY2 by demonstrating their dose-dependent competitive binding to Spindlins, the key protein domains and rapidly evolving residues and exons that drive the competition, and how the competition is likely between complex multimers. Our findings have broad implications for the mechanics of evolutionary arms and how competition between sex chromosomes influences X- versus Y-sperm fitness and sex ratio.
A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae
34215Tolosana, I., Willis, K., Gribble, M. et al., Nature Communications, 16:206. 2025-01-07 09:21:41.
Genetic control – the deliberate introduction of genetic traits to control a pest or vector population – offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings, but hesitancy due to their invasive and persistent nature may delay their implementation. Here, instead, we describe a self-limiting strategy, designed to have geographically and temporally restricted effect, based on a Y chromosome-linked genome editor (YLE). The YLE comprises a CRISPR-Cas9 construct that is always inherited by males yet generates an autosomal dominant mutation that is transmitted to over 90% of the offspring and results in female-specific sterility. To our knowledge, our system represents a pioneering approach in the engineering of the Y chromosome to generate a genetic control strain for mosquitoes. Mathematical modelling shows that this YLE technology is up to seven times more efficient for population suppression than optimal versions of other self-limiting strategies, such as the widely used Sterile Insect Technique or the Release of Insects carrying a Dominant Lethal gene.
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.
Gene drives and population persistence vs elimination: The impact of spatial structure and inbreeding at low density
20529P. J. Beaghton and A. Burt, Theoretical Population Biology, 2022-03-03 08:28:52.
Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same is true when spatial processes play a role. In species with an appropriate biology it is possible that drive-induced reductions in density might lead to increased inbreeding, reducing the efficacy of drive, eventually leading to suppression rather than elimination, regardless of how strong the drive is. To investigate this question we analyse a series of explicitly solvable stochastic models considering a range of scenarios for the relative timing of mating, reproduction, and dispersal and analyse the impact of two different types of gene drive, a Driving Y chromosome and a homing construct targeting an essential gene. We find in all cases a sufficiently strong Driving Y will go to fixation and the population will be eliminated, except in the one life history scenario (reproduction and mating in patches followed by dispersal) where low density leads to increased inbreeding, in which case the population persists indefinitely, tending to either a stable equilibrium or a limit cycle. These dynamics arise because Driving Y males have reduced mating success, particularly at low densities, due to having fewer sisters to mate with. Increased inbreeding at low densities can also prevent a homing construct from eliminating a population. For both types of drive, if there is strong inbreeding depression, then the population cannot be rescued by inbreeding and it is eliminated. These results highlight the potentially critical role that low-density-induced inbreeding and inbreeding depression (and, by extension, other sources of Allee effects) can have on the eventual impact of a gene drive on a target population.
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.
Synthetic sex ratio distorters based on CRISPR for the control of harmful insect populations
19369Fasulo, B., Meccariello, A., Papathanos, P. A., and Windbichler, N., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 16:55:38.
Since the overall reproductive output of a population is typically determined by the fertility of its females, which are rate-limiting in gamete production, a successful way to genetically control a population should involve artificially biasing the sex ratio towards males. In male heterogametic species, this could be achieved by the expression of a transgene-encoded endonuclease during spermatogenesis that would target and "shred" the X chromosome at several loci. This would prevent the transmission of X chromosome bearing gametes to the progeny, generating only males. Recent developments in molecular and synthetic biology have provided genome editing tools with great potential to engineer the genome of different species. Given the targeting flexibility of CRISPR-based endonucleases, it may now be possible to test whether X chromosome shredding has the potential to become a universal strategy to genetically control a wide variety of insect pests, of both agricultural and public health relevance.
Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes
18819F. Pajpach, T. Wu, L. Shearwin-Whyatt, K. Jones and F. Grützner, Genes, 12. 2021-08-28 15:33:36.
Segregation of chromosomes is a multistep process occurring both at mitosis and meiosis to ensure that daughter cells receive a complete set of genetic information. Critical components in the chromosome segregation include centromeres, kinetochores, components of sister chromatid and homologous chromosomes cohesion, microtubule organizing centres, and spindles. Based on the cytological work in the grasshopper Brachystola, it has been accepted for decades that segregation of homologs at meiosis is fundamentally random. This ensures that alleles on chromosomes have equal chance to be transmitted to progeny. At the same time mechanisms of meiotic drive and an increasing number of other examples of non-random segregation of autosomes and sex chromosomes provide insights into the underlying mechanisms of chromosome segregation but also question the textbook dogma of random chromosome segregation. Recent advances provide a better understanding of meiotic drive as a prominent force where cellular and chromosomal changes allow autosomes to bias their segregation. Less understood are mechanisms explaining observations that autosomal heteromorphism may cause biased segregation and regulate alternating segregation of multiple sex chromosome systems or translocation heterozygotes as an extreme case of non-random segregation. We speculate that molecular and cytological mechanisms of non-random segregation might be common in these cases and that there might be a continuous transition between random and non-random segregation which may play a role in the evolution of sexually antagonistic genes and sex chromosome evolution.
Haldane’s duel: intragenomic conflict, selfish Y chromosomes and speciation
17509S. W. Roy, Trends in Genetics, 2021-06-21 14:14:05.
Haldane?s rule, which states that the heterogametic sex (XY or ZW females) fares more poorly in interspecific hybrids, is generally attributed to absence of one of the two species' X/Z chromosomes. However, Haldane?s rule is also observed in mouse placentas despite paternal X silencing. This pattern could reflect Y chromosomes having evolved to promote growth due to maternal?paternal conflict. If so, balanced sex investment arises from a complex intra- and intergenomic duel.
The New Yorker Magazine: Gene Drives as a Tool for Saving Nature
16277E. Heber, Island Conservation, 2021-01-03 17:07:04.
In a recent New Yorker Magazine article, entitled “CRISPR and the Splice to Survive,” journalist and best-selling author Elizabeth Kolbert dives into the world of gene drive research. She touches on aspects of gene drive research from altering the toxin produced by cane toads to recovering nearly-extinct trees to eradicating invasive mice through attrition, all to understand the possibilities this tool could hold.
Sequence analysis in Bos taurus reveals pervasiveness of X–Y arms races in mammalian lineages
15219J. F. Hughes, H. Skaletsky, T. Pyntikova, N. Koutseva, T. Raudsepp, L. G. Brown, D. W. Bellott, T.-J. Cho, S. Dugan-Rocha, Z. Khan, C. Kremitzki, C. Fronick, T. A. Graves-Lindsay, L. Fulton, W. C. Warren, R. K. Wilson, E. Owens, J. E. Womack, W. J. Murphy, Genome Research, 2020-11-18 16:58:55.
Here, we provide evidence that suppression of X–Y crossing-over unleashed a second dynamic: selfish X–Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of Bos taurus (bull) and find it to be dominated by massive, lineage-specific amplification of testis-expressed gene families, making it the most gene-dense Y Chromosome sequenced to date. As in mice, an X-linked homolog of a bull Y-amplified gene has become testis-specific and amplified. This evolutionary convergence implies that lineage-specific X–Y coevolution through gene amplification, and the selfish forces underlying this phenomenon, were dominatingly powerful among diverse mammalian lineages. Together with Y gene decay, X–Y arms races molded mammalian sex chromosomes and influenced the course of mammalian evolution.
The bull Y chromosome has evolved to bully its way into gametes
15217Whitehead Institute for Biomedical Research, Phys Org, 2020-11-18 16:54:40.
In a new study, published Nov. 18 in the journal Genome Research, scientists in the lab of Whitehead Institute Member David Page present the first ever full, high-resolution sequence of the Y chromosome of a Hereford bull. The research, more than a decade in the making, suggests that bulls' Y chromosomes have evolved dozens of copies of the same genes in a selfish attempt to make more males—a move that is countered in the female-determining X chromosome. This insight into the forces that govern sex chromosome behavior and evolution will help scientists in Page's lab study genetic differences between males and females and how they play out in health and disease across every part of the body, Page added.
Nix alone is sufficient to convert female Aedes aegypti into fertile males and myo-sex is needed for male flight
13780A. Aryan, M. A. E. Anderson, J. K. Biedler, Y. M. Qi, J. M. Overcash, A. N. Naumenko, M. V. Sharakhova, C. H. Mao, Z. N. Adelman and Z. J. Tu, Proceedings of the National Academy of Sciences of the United States of America, 117:17702-17709. 2020-07-28 13:17:04.
Here, we report the generation of multiple transgenic lines that express Nix under the control of its own promoter. Genetic and molecular analyses of these lines provided insights unattainable from previous transient experiments. We show that the Nix transgene alone, in the absence of the M-locus, was sufficient to convert females into males with all male-specific sexually dimorphic features and male-like gene expression.
The Y Chromosome as a Battleground for Intragenomic Conflict
11962D. Bachtrog, Trends in Genetics, 2020-05-21 18:10:11.
Recurrent sex chromosome drive can have profound ecological, evolutionary, and cellular impacts and account for unique features of sex chromosomes.
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.
A fly model establishes distinct mechanisms for synthetic CRISPR/Cas9 sex distorters
7973B. Fasulo, A. Meccariello, M. Morgan, C. Borufka, P. A. Papathanos and N. Windbichler, PLOS Genetics, 16:e1008647. 2020-03-13 15:02:19.
Author summary Harmful insect populations can be eliminated for a lack of females if they are made to produce mostly male offspring. There are genes that occur naturally that make males produce mostly sons and, although we don’t know exactly how they work, this appears to coincide with damage to the X-chromosome during the production of sperm. Recently, we showed in a mosquito species that such sex-biasing genes could also be constructed artificially from first principles. To better understand if this works in other species too, we designed and built male-biasing genes of two types in the fruit fly and determined what is needed to for a shift towards males. We show how different ways of cutting the X-chromosome DNA at different times with CRISPR, results in distinct outcomes and started to ask what cellular processes are involved in this. These models will help us to design such genes for the control of insect species that transmit disease or threaten crops.
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.
Plasmodium falciparum (Haemosporodia: Plasmodiidae) and O’nyong-nyong virus development in a transgenic Anopheles gambiae (Diptera: Culicidae) strain
5634Mumford, J. D., C. A. Long, S. C. Weaver, K. Miura, E. Wang, R. Rotenberry, E. M. Dotson and M. Q. Benedict, " Journal of Medical Entomology, 56:936-941. 2019-12-17 16:55:10.
ransgenic Anopheles gambiae Giles (Diptera: Culicidae) mosquitoes have been developed that confer sexual sterility on males that carry a transgene encoding a protein which cuts ribosomal DNA. A relevant risk concern with transgenic mosquitoes is that their capacity to transmit known pathogens could be greater than the unmodified form. In this study, the ability to develop two human pathogens in these transgenic mosquitoes carrying a homing endonuclease which is expressed in the testes was compared with its nontransgenic siblings. Infections were performed with Plasmodium falciparum (Welch) and o’nyong-nyong virus (ONNV) and the results between the transgenic and nontransgenic sibling females were compared. There was no difference observed with ONNV isolate SG650 in intrathoracic infections or the 50% oral infectious dose measured at 14 d postinfection or in mean body titers. Some significant differences were observed for leg titers at the medium and highest doses for those individuals in which virus titer could be detected. No consistent difference was observed between the transgenic and nontransgenic comparator females in their ability to develop P. falciparum NF54 strain parasites. This particular transgene caused no significant effect in the ability of mosquitoes to become infected by these two pathogens in this genetic background. These results are discussed in the context of risk to human health if these transgenic individuals were present in the environment.
Genetic Control of Mosquitoes
5588Alphey, L., Annual Review of Entomology, 59:205-224. 2019-12-16 19:01:55.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.
A genetic system for biasing the sex ratio in mice
3952Yosef, IEB, Liat; Globus, Rea; Shlomovitz, Inbar; Munitz, Ariel; Gerlic, Motti; Qimron, Udi, EMBO reports, 20:e48269. 2019-01-10 00:00:00.
Biasing the sex ratio of populations of different organisms, including plants, insects, crustacean, and fish, has been demonstrated by genetic and non-genetic approaches. However, biasing the sex ratio of mammalian populations has not been demonstrated genetically. Here, we provide a first proof of concept for such a genetic system in mammals by crossing two genetically engineered mouse lines. The maternal line encodes a functional Cas9 protein on an autosomal chromosome, whereas the paternal line encodes guide RNAs on the Y chromosome targeting vital mouse genes. After fertilization, the presence of both the Y-encoded guide RNAs from the paternal sperm and the Cas9 protein from the maternal egg targets the vital genes in males. We show that these genes are specifically targeted in males and that this breeding consequently self-destructs solely males. Our results pave the way for a genetic system that allows biased sex production of livestock.
Genetic manipulation of sex ratio in mammals: the Reaper comes for Mickey
3947Smanski, MJZ, David, EMBO reports, 20:e48577. 2019-01-05 00:00:00.
In most animals, sexual reproduction results in a 1:1 ratio of females to males. For several sectors of agriculture, for example, milk or egg production, only a single sex is needed. Biasing the sex ratio so that only offspring of the desired sex are produced has the potential to increase breeding efficiency. In this issue of EMBO Reports, Yosef et al [1] demonstrate a genetic approach to bias the sex ratio in mice by specifically disrupting essential genes in male embryos. Their approach is an important first step toward generating sex-ratio biasing applications for agriculture
Gene drive to reduce malaria transmission in sub-Saharan Africa
3963Burt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K., Journal of Responsible Innovation, 5:S66-S80. 2018-01-21 00:00:00.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of mosquitoes and/or reduce vector competence. As with any control measure, due attention should be paid to the possible evolution of resistance. No gene drive construct has yet been reported that is "field-ready" for release, and when such constructs are developed, they should be assessed on a case-by-case basis. Gene drive approaches to vector control promise to have a number of key features that motivate their continued development, and scrutiny, by all concerned.
Redkmer: An assembly-free pipeline for the identification of abundant and specific X-chromosome target sequences for X-shredding by CRISPR endonucleases
4006Papathanos, PAW, Nikolai, CRISPR Journal, 1:88-98. 2018-01-04 00:00:00.
CRISPR-based synthetic sex ratio distorters, which operate by shredding the X-chromosome during male meiosis, are promising tools for the area-wide control of harmful insect pest or disease vector species. X-shredders have been proposed as tools to suppress insect populations by biasing the sex ratio of the wild population toward males, thus reducing its natural reproductive potential. However, to build synthetic X-shredders based on CRISPR, the selection of gRNA targets, in the form of high-copy sequence repeats on the X chromosome of a given species, is difficult, since such repeats are not accurately resolved in genome assemblies and cannot be assigned to chromosomes with confidence. We have therefore developed the redkmer computational pipeline, designed to identify short and highly abundant sequence elements occurring uniquely on the X chromosome. Redkmer was designed to use as input minimally processed whole genome sequence data from males and females. We tested redkmer with short- and long-read whole genome sequence data of Anopheles gambiae, the major vector of human malaria, in which the X-shredding paradigm was originally developed. Redkmer established long reads as chromosomal proxies with excellent correlation to the genome assembly and used them to rank X-candidate kmers for their level of X-specificity and abundance. Among these, a high-confidence set of 25-mers was identified, many belonging to previously known X-chromosome repeats of Anopheles gambiae,including the ribosomal gene array and the selfish elements harbored within it. Data from a control strain, in which these repeats are shared with the Y chromosome, confirmed the elimination of these kmers during filtering. Finally, we show that redkmer output can be linked directly to gRNA selection and off-target prediction. In addition, the output of redkmer, including the prediction of chromosomal origin of single-molecule long reads and chromosome specific kmers, could also be used for the characterization of other biologically relevant sex chromosome sequences, a task that is frequently hampered by the repetitiveness of sex chromosome sequence content.
Self-limiting population genetic control with sex-linked genome editors
3965Burt, AD, Anne, Proceedings of the Royal Society B: Biological Sciences, 285:20180776. 2018-01-03 00:00:00.
In male heterogametic species the Y chromosome is transmitted solely from fathers to sons, and is selected for based only on its impacts on male fitness. This fact can be exploited to develop efficient pest control strategies that use Y-linked editors to disrupt the fitness of female descendants. With simple population genetic and dynamic models we show that Y-linked editors can be substantially more efficient than other self-limiting strategies and, while not as efficient as gene drive approaches, are expected to have less impact on non-target populations with which there is some gene flow. Efficiency can be further augmented by simultaneously releasing an autosomal X-shredder construct, in either the same or different males. Y-linked editors may be an attractive option to consider when efficient control of a species is desired in some locales but not others.
Gene drive: Evolved and synthetic
3964Burt, AC, Andrea, ACS Chemical Biology, 13:343-346. 2018-01-02 00:00:00.
Drive is a process of accelerated inheritance from one generation to the next that allows some genes to spread rapidly through populations even if they do not contribute to—or indeed even if they detract from—organismal survival and reproduction. Genetic elements that can spread by drive include gametic and zygotic killers, meiotic drivers, homing endonuclease genes, B chromosomes, and transposable elements. The fact that gene drive can lead to the spread of fitness-reducing traits (including lethality and sterility) makes it an attractive process to consider exploiting to control disease vectors and other pests. There are a number of efforts to develop synthetic gene drive systems, particularly focused on the mosquito-borne diseases that continue to plague us.
Sry gene drive for rodent control: Reply to Gemmell and Tompkins
4051Kanavy, DS, M., Trends in Ecology & Evolution, 32:315-316. 2017-01-09 00:00:00.
We would like to thank Gemmell and Tompkins for their interest and comments onthe articlebyPiaggioet al. [1].Theissues raised by Gemmell and Tompkins [2] are very pertinent, and they correctly identified that the format of the article did not lend itself to a comprehensive discussion of the ideas of using gene drives in mice. The method being considered in the Piaggio et al. article is to utilize a naturally occurring t-allele transgene (Tg) to sex-bias amouse population, causing it to crash. Inserting the sex-determining region on the Y chromosome (Sry) into the Tg allows biased inheritance where the majority of the offspring born are phenotypically male.
Vector control with driving Y chromosomes: modelling the evolution of resistance
4030Beaghton, AB, P. J.; Burt, A., Malaria Journal, 16:286. 2017-01-08 00:00:00.
: The introduction of new malaria control interventions has often led to the evolution of resistance, both of the parasite to new drugs and of the mosquito vector to new insecticides, compromising the efficacy of the interventions. Recent progress in molecular and population biology raises the possibility of new genetic-based interventions, and the potential for resistance to evolve against these should be considered. Here, population modelling is used to determine the main factors affecting the likelihood that resistance will evolve against a synthetic, nuclease-based driving Y chromosome that produces a male-biased sex ratio. Methods: A combination of deterministic differential equation models and stochastic analyses involving branching processes and Gillespie simulations is utilized to assess the probability that resistance evolves against a driving Y that otherwise is strong enough to eliminate the target population. The model considers resistance due to changes at the target site such that they are no longer cleaved by the nuclease, and due to trans-acting autosomal suppressor alleles. Results: The probability that resistance evolves increases with the mutation rate and the intrinsic rate of increase of the population, and decreases with the strength of drive and any pleiotropic fitness costs of the resistant allele. In seasonally varying environments, the time of release can also affect the probability of resistance evolving. Trans-acting suppressor alleles are more likely to suffer stochastic loss at low frequencies than target site resistant alleles. Conclusions: As with any other intervention, there is a risk that resistance will evolve to new genetic approaches to vector control, and steps should be taken to minimize this probability. Two design features that should help in this regard are to reduce the rate at which resistant mutations arise, and to target sequences such that if they do arise, they impose a significant fitness cost on the mosquito.
B Chromosomes – A matter of chromosome drive
4048Houben, A, Frontiers in Plant Science, 8:210. 2017-01-06 00:00:00.
B chromosomes are supernumerary chromosomes which are often preferentially inherited, deviating from usual Mendelian segregation. The balance between the so-called chromosome drive and the negative effects that the presence of Bs applies on the fitness of their host determines the frequency of Bs in a particular population. Drive is the key for understanding most B chromosomes. Drive occurs in many ways at pre-meiotic, meiotic or post-meiotic divisions, but the molecular mechanism remains unclear. The cellular mechanism of drive is reviewed based on the findings obtained for the B chromosomes of rye, maize and other species. How novel analytical tools will expand our ability to uncover the biology of B chromosome drive is discussed.
Gene drive through a landscape: Reaction-diffusion models of population suppression and elimination by a sex ratio distorter
4081Beaghton, AB, P. J.; Burt, A., Theoretical Population Biology, 108:51-69. 2016-01-19 00:00:00.
Some genes or gene complexes are transmitted from parents to offsprihg at a greater-than-Mendelian rate, and can spread and persist in populations even if they cause some harm to the individuals carrying them. Such genes may be useful for controlling populations or species that are harmful. Driving-Y chromosomes may be particularly potent in this regard, as they produce a male-biased sex ratio that, if sufficiently extreme, can lead to population elimination. To better understand the potential of such genes to spread over a landscape, we have developed a series of reaction-diffusion models of a driving-Y chromosome in 1-D and radially-symmetric 2-D unbounded domains. The wild-type system at carrying capacity is found to be unstable to the introduction of driving-Y males for all models investigated. Numerical solutions exhibit travelling wave pulses and fronts, and analytical and semi-analytical solutions for the asymptotic wave speed under bounded initial conditions are derived. The driving-Y male invades the wild-type equilibrium state at the front of the wave and completely replaces the wild-type males, leaving behind, at the tail of the wave, a reduced- or zero-population state of females and driving-Y males only. In our simplest model of a population with one life stage and density-dependent mortality, wave speed depends on the strength of drive and the diffusion rate of Y-drive males, and is independent of the population dynamic consequences (suppression or elimination). Incorporating an immobile juvenile stage of fixed duration into the model reduces wave speed approximately in proportion to the relative time spent as a juvenile. If females mate just once in their life, storing sperm for subsequent reproduction, then wave speed depends on the movement of mated females as well as Y-drive males, and may be faster or slower than in the multiple-mating model, depending on the relative duration of juvenile and adult life stages. Numerical solutions are shown for parameter values that may in part be representative for Anopheles gambiae, the primary vector of malaria in sub-Saharan Africa. (C) 2015 The Authors. Published by Elsevier Inc.
Mechanisms of sex determination and transmission ratio distortion in Aedes aegypti
4089Hoang, KPT, T. M.; Ho, T. X.; Le, V. S., Parasites & Vectors, 9:49. 2016-01-07 00:00:00.
: More effective mosquito control strategies are urgently required due to the increasing prevalence of insecticide resistance. The sterile insect technique (SIT) and the release of insects carrying a dominant lethal allele (RIDL) are two proposed methods for environmentally-friendly, species-targeted population control. These methods may be more suitable for developing countries if producers reduce the cost of rearing insects. The cost of control programs could be reduced by producing all-male mosquito populations to circumvent the isolation of females before release without reducing male mating competitiveness caused by transgenes. Results: An RNAi construct targeting the RNA recognition motif of the Aedes aegypti transformer-2 (tra-2) gene does not trigger female-to-male sex conversion as commonly observed among dipterous insects. Instead, homozygous insects show greater mortality among m-chromosome-bearing sperm and mm zygotes, yielding up to 100 % males in the subsequent generations. The performance of transgenic males was not significantly different to wild-type males in narrow-cage competitive mating experiments. Conclusion: Our data provide preliminary evidence that the knockdown of Ae. aegypti tra-2 gene expression causes segregation distortion acting at the level of gametic function, which is reinforced by sex-specific zygotic lethality. This finding could promote the development of new synthetic sex distorter systems for the production of genetic sexing mosquito strains.
Coevolutionary dynamics of polyandry and sex-linked meiotic drive
4118Holman, LP, T. A. R.; Wedell, N.; Kokko, H., Evolution, 69:709-720. 2015-01-16 00:00:00.
Segregation distorters located on sex chromosomes are predicted to sweep to fixation and cause extinction via a shortage of one sex, but in nature they are often found at low, stable frequencies. One potential resolution to this longstanding puzzle involves female multiple mating (polyandry). Because many meiotic drivers severely reduce the sperm competitive ability of their male carriers, females are predicted to evolve more frequent polyandry and thereby promote sperm competition when a meiotic driver invades. Consequently, the driving chromosome's relative fitness should decline, halting or reversing its spread. We used formal modeling to show that this initially appealing hypothesis cannot resolve the puzzle alone: other selective pressures (e.g., low fitness of drive homozygotes) are required to establish a stable meiotic drive polymorphism. However, polyandry and meiotic drive can strongly affect one another's frequency, and polyandrous populations may be resistant to the invasion of rare drive mutants.
Sex chromosome drive
4117Helleu, QG, P. R.; Montchamp-Moreau, C., Cold Spring Harbor Perspectives in Biology, 7:a017616. 2015-01-15 00:00:00.
Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are over represented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species.
On the origin of sex chromosomes from meiotic drive
4127Ubeda, FP, M. M.; Wild, G., Proceedings of the Royal Society B-Biological Sciences, 282:20141932. 2015-01-05 00:00:00.
Most animals and many plants make use of specialized chromosomes (sex chromosomes) to determine an individual's sex. Best known are the XY and ZW sex-determination systems. Despite having evolved numerous times, sex chromosomes present something of an evolutionary puzzle. At their origin, alleles that dictate development as one sex or the other (primitive sex chromosomes) face a selective penalty, as they will be found more often in the more abundant sex. How is it possible that primitive sex chromosomes overcome this disadvantage? Any theory for the origin of sex chromosomes must identify the benefit that outweighs this cost and enables a sex-determining mutation to establish in the population. Here we show that a new sex-determining allele succeeds when linked to a sex-specific meiotic driver. The new sex-determining allele benefits from confining the driving allele to the sex in which it gains the benefit of drive. Our model requires few special assumptions and is sufficiently general to apply to the evolution of sex chromosomes in outbreeding cosexual or dioecious species. We highlight predictions of the model that can discriminate between this and previous theories of sex-chromosome origins.
Genetic Control of Mosquitoes.
5597Alphey, L., Annual Review of Entomology, 59:205-224. 2014-12-17 15:50:24.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.
A synthetic sex ratio distortion system for the control of the human malaria mosquito
4140Galizi, RD, L. A.; Menichelli, M.; Bernardini, F.; Deredec, A.; Burt, A.; Stoddard, B. L.; Windbichler, N.; Crisanti, A., Nature Communications, 5:3977. 2014-01-18 00:00:00.
It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action of naturally occurring sex distorters and the prevalence of co-evolving suppressors has hampered their use for control. Here we generate a synthetic sex distortion system by exploiting the specificity of the homing endonuclease I-PpoI, which is able to selectively cleave ribosomal gene sequences of the malaria vector Anopheles gambiae that are located exclusively on the mosquito's X chromosome. We combine structure-based protein engineering and molecular genetics to restrict the activity of the potentially toxic endonuclease to spermatogenesis. Shredding of the paternal X chromosome prevents it from being transmitted to the next generation, resulting in fully fertile mosquito strains that produce >95% male offspring. We demonstrate that distorter male mosquitoes can efficiently suppress caged wild-type mosquito populations, providing the foundation for a new class of genetic vector control strategies.
Sex-ratio meiotic drive and interspecific competition
4159Unckless, RLC, A. G., Journal of Evolutionary Biology, 27:1513-1521. 2014-01-17 00:00:00.
It has long been known that processes occurring within a species may impact the interactions between species. For example, as competitive ability is sensitive to parameters including reproductive rate, carrying capacity and competition efficiency, the outcome of interspecific competition may be influenced by any process that alters these attributes. Although several such scenarios have been discussed, the influence of selfish genetic elements within one species on competition between species has not received theoretical treatment. We show that, with strong competition, sex-ratio meiotic drive systems can result in a significant shift in community composition because the effective birth rate in the population may be increased by a female-biased sex ratio. Using empirical data, we attempt to estimate the magnitude of this effect in several Drosophila species. We infer that meiotic drive elements, selfish genetic elements within species, can provide a substantial competitive advantage to that species within a community.
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.
Changes in sperm tail development associated with Y chromosome meiotic drive leading to an excess of males in the medfly Ceratitis capitata (Diptera: Tephritidae)
4218Rendon, PAB, R. D.; Wood, R. J., Biological Journal of the Linnean Society, 101:351-359. 2010-01-16 00:00:00.
The Mediterranean fruit fly Ceratitis capitata (Wied.) normally produces the sexes in equal ratio but strains carrying the Y chromosome meiotic drive MP (male-producing) factor show an excess of males. This is associated with a loss of sperm, and abnormal sperm structure in terms of multiple axonemes, atypical numbers of mitochondrial derivatives, and sometimes an incorrect initial orientation of paracrystalline bodies to the axoneme. Sperms are bundled together within spermatocysts, and those with depleted content and abnormalities occur in the same MP testes as normal spermatocysts. The maximum number of sperms per cyst in control strains was 256, each with a single axoneme originating from a single centriole (kinetosome). The maximum per cyst in MP strains was also 256 but MP cysts contained up to 300 axonemes, providing evidence of multiplication of centrioles. The structural changes in MP sperm are discussed in relation to similar abnormalities reported in the mosquito Aedes aegypti inheriting the Y chromosome meiotic drive haplotype MD. The evolutionary significance of this phenomenon is considered. (C) 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101, 351-359.
Segregation distortion and the evolution of sex-determining mechanisms
4216Kozielska, MW, F. J.; Beukeboom, L. W.; Pen, I., Heredity, 104:100-112. 2010-01-14 00:00:00.
Segregation distorters are alleles that distort normal segregation in their own favour. Sex chromosomal distorters lead to biased sex ratios, and the presence of such distorters, therefore, may induce selection for a change in the mechanism of sex determination. The evolutionary dynamics of distorter-induced changes in sex determination has only been studied in some specific systems. Here, we present a generic model for this process. We consider three scenarios: a driving X chromosome, a driving Y chromosome and a driving autosome with a male-determining factor. We investigate how the invasion prospects of a new sex-determining factor are affected by the strength of distortion and the fitness effect of the distorting allele. Our models show that in many cases, segregation distortion does create selection pressure, allowing novel sex-determining alleles to spread. When distortion leads to female-biased sex ratios, a new masculinizing gene can invade, leading to a new male heterogametic system. When distortion leads to male-biased sex ratios, a feminizing factor can invade and cause a switch to female heterogamety. In many cases, the distorter-induced change in the sex-determining system eventually leads to loss of the distorter from the population. Hence, the presence of sex chromosomal distorters will often only be transient, and the distorters may remain unnoticed. The role of segregation distortion in the evolution of sex determination may, therefore, be underestimated. Heredity (2010) 104, 100-112; doi:10.1038/hdy.2009.104; published online 12 August 2009
The population genetics of using homing endonuclease genes in vector and pest management
4234Deredec, AB, A.; Godfray, H. C. J., Genetics, 179:2013-2026. 2008-01-12 00:00:00.
Homing endonuclease genes (HEGs) encode proteins that in the heterozygous state cause double- strand breaks in the homologous chromosome at the precise position opposite the HFG. If the double-strand break is repaired using the homologous chromosome, the HEG becomes homozygous, and this represents it Powerful genetic drive mechanism that might he used as it tool managing vector or pest populations. HEGs may be used to decrease population fitness to drive down population densities (possibly causing local extinction) or, in disease vectors, to knock out a gene required for pathogen transmission. The relative advantages of HEGs thia target viability or fecundity, that are active in one sex or both, and whose target. is expressed before or after homing are explored. The conditions under which escape mutants arise are also analyzed. A different strategy is to place HEGs on the Y chromosome that cause one, or more breaks on the X chromosome and so disrupt. sex ratio. This strategy can cause severe sex-ratio biases with efficiencies that depend on the details of sperm Competition and zygote mortality. This strategy is probably less susceptible to escape mutants, especially when multiple X shredders are used.
Meiotic drive by the Y-linked D gene in Aedes aegypti (L.) (Diptera : Culicidae) is associated with disruption of spermiogenesis, leading to premature senescence of spermatozoa
4253Owusu-Daaku, KOB, R. D.; Wood, R. J., Arthropod Structure & Development, 36:233-243. 2007-01-11 00:00:00.
Y chromosome meiotic drive in the mosquito Aedes aegypti, due to the gene D (Distorter) in coupling with M (male determination) [the MD haplotype], is associated with spermiogenic disruption, leading to senescence, at a rate Proportionate to male excess. Spermiogenesis was compared between 'Enhanced Mutant' males with a strongly female-depleted sex ratio (8.9% females), 'Mutant' males showing a lesser degree of distortion (38.3% females), and two controls with normal sex ratios (51.2% and 49.2% females). Sections of testes dissected front mature pupae and adults aged 0, 4, 8, 12 and 16 days were examined by transmission electron microscopy. A difference between Mutant and control spermiogenesis was apparent as early as the pupal stage when some Mutant spermatids showed extra tail elements (axonemes and/or mitochondrial derivatives). The same was true of Enhanced Mutant males but to a more extreme degree. Sperm senescence was evident in Enhanced Mutant testes from day 0 of adult life but in Mutant testes not until day 4. Progressive disorganisation was associated with many loose organelles, and disturbance of the anterior-posterior axis of gamete differentiation within the testis. Degenerative changes of a similar kind in the controls did not become apparent until day 8. These findings are discussed with respect to other characteristics of this meiotic drive system, in terms of a theory of inhibition of reduction division in spermatogenesis associated with fragmentation of the X chromosome, leading to the formation of a restitution nucleus as early as rnetaphase 1. (c) 2007 Elsevier Ltd. All rights reserved.
Introducing desirable transgenes into insect populations using Y-linked meiotic drive – A theoretical assessment
4251Huang, YXM, K.; Lloyd, A. L.; Gould, F., Evolution, 61:717-726. 2007-01-09 00:00:00.
The use of genetic drive mechanisms to replace native mosquito genotypes with individuals bearing antipathogen transgenes is a potential strategy for repressing insect transmission of human diseases such as malaria and dengue. Antipathogen transgenes have been developed and tested, but efficient gene drive mechanisms are lacking. Here we theoretically assess the feasibility of introducing antipathogen genes into wild Aedes aegypti populations by using a naturally occurring meiotic drive system. We consider the release of males having both a Winked meiotic drive gene and an X-linked drive-insensitive response allele to which an antipathogen gene is linked. We use mathematical models and computer simulations to determine how the post-introduction dynamics of the antipathogen gene are affected by specific genetic characteristics of the system. The results show that when the natural population is uniformly sensitive to the meiotic drive gene, the antipathogen gene may be driven close to fixation if the fitness costs of the drive gene, the insensitive response allele, and the antipathogen gene are low. However, when the natural population has a small proportion of an X-linked insensitive response allele or an autosomal gene that strongly reduces the effect of the drive gene, the antipathogen gene does not spread if it has an associated fitness cost. Our modeling results provide a theoretical foundation for further experimental tests.
Cage trials using an endogenous meiotic drive gene in the mosquito Aedes aegypti to promote population replacement
4262Cha, SJM, A.; Chadee, D. D.; Severson, D. W., American Journal of Tropical Medicine and Hygiene, 74:62-68. 2006-01-20 00:00:00.
Control of arthropod-borne diseases based on population replacement with genetically modified noncompetent vectors has been proposed as a promising alternative to conventional control strategies. Due to likely fitness costs associated with vectors manipulated to carry anti-pathogen effector genes, the effector genes will need to be coupled with a strong drive system to rapidly sweep them into natural populations. Endogenous meiotic drive systems have strong and stable population replacement potential, and have previously been reported in two mosquito species: Aedes aegypti and Culex pipiens. To investigate the influence of an endogenous meiotic drive gene on Ae. aegypti population dynamics, we established three experimental population types that were initiated with 100%, 10%, and 1% male mosquitoes carrying a strong meiotic driver (T37 strain) and 100% sensitive females (RED strain), respectively. Among the 100% and 10% populations, early generations were highly male biased, which reflected the effects of the meiotic driver, and remained more than 60% male by the F-15. A genetic marker tightly linked with the meiotic driver on chromosome 1 showed strong selection for the T37 strain-specific allele. Similar but reduced effects of the meiotic driver were also observed in the 1% populations. These results suggest that release of A e. aegypti males carrying a strong meiotic driver into drive sensitive populations can be an effective tool for population replacement, and provide a foundation for additional studies including both experimental populations and simulations by mathematical modeling.
Population dynamics of an endogenous meiotic drive system in Aedes aegypti in Trinidad
4260Cha, SJC, D. D.; Severson, D. W., American Journal of Tropical Medicine and Hygiene, 75:70-77. 2006-01-18 00:00:00.
An endogenous meiotic drive system was previously reported to be segregating in the yellow fever mosquito Aedes aegypti L. (Diptera: Culicidae) population in Trinidad. The meiotic driver (M-D) is tightly linked to the male determining locus and selectively targets sensitive responders linked to the female determining allele, causing fragmentation of female gametes. This results in highly male-biased progeny. The M-D system was initially studied as a genetic tool for population control with limited success, but recently interest has focused on its potential for population replacement. This study examines the distribution and dynamics of the M-D system in Trinidad natural populations. We obtained ovitrap samples from seven geographically distinct regions and determined the allele frequencies of the driver (M-D) and sensitive (m(s)) versus insensitive (m(i)) responders, respectively. Frequencies of the M-D allele ranged from 0.1 to 0.5 and were low at the two major port cities, Port of Spain and San Fernando, suggesting the effects of frequent immigration by non-driving genotypes. Frequencies of the m(i) allele ranged from 0.4 to 0.7, suggesting the effects of strong selection by the driver. In addition, our results show that the driver and sensitivity of responders in the Trinidad populations are highly polymorphic. Continued studies of the dynamics of the M-D system in natural populations are critical to considerations of its use in population replacement.
Male biased sex ratio in the Mediterranean fruit fly Ceratitis capitata, an example of Y-chromosome meiotic drive
4268Shahjahan, RMR, P. A.; Cook, L. M.; Wood, R. J., Heredity, 96:464-470. 2006-01-06 00:00:00.
A case of Y-chromosome meiotic drive is reported in the Mediterranean fruit fly Ceratitis capitata. It arose in an irradiated male and results in excess of males. Male excess is inherited strictly from father to son. A Y-linked factor MP (male producer) is proposed. Higher drive can be selected, but distortion declines rapidly in the absence of selection. Hybrid males from crosses between driving males and nondriving females also show drive but to a reduced extent, suggesting the action of suppressors. Sex ratio distortion is independent of postzygotic mortality, and is not associated with an obvious chromosome arrangement. Spermiogenesis in driving males is characterised by abnormalities in sperm tails and reduced numbers in some sperm cysts, whereas neighbouring cysts of the same MP testis are essentially wild type. The average number of missing sperms plus deformed sperms approximates to the average depression in female recovery among the progenies of siblings, suggesting that most of the missing or abnormal sperms would have given rise to females, that is, they would have been X-bearing. To explain the heterogeneity between neighbouring cysts, a theory is proposed that links it to variation in X-chromosome sensitivity to MP, arising by random suppression of the genetic basis of sensitivity during the six mitotic divisions in the origin of the cyst from its stem cell before meiosis.
Reinvestigation of an endogenous meiotic drive system in the mosquito, Aedes aegypti (Diptera : Culicidae)
4295Mori, AC, D. D.; Graham, D. H.; Severson, D. W., Journal of Medical Entomology, 41:1027-1033. 2004-01-13 00:00:00.
We have initiated efforts to determine the molecular basis for the M-D meiotic drive system in the mosquito, Aedes aegypti. The effect of the M-D gene is a highly male-biased sex ratio, but varies depending on the frequency and sensitivity of a susceptible responder m(s) allele. The M-D system has potential as a mechanism for driving trangenes for pathogen resistance into natural Ae. aegypti populations. Because all previously existing laboratory strains carrying the M-D gene have been lost, we have selected for a new strain, T37, that carries a strong driver. Matings between T37 males and drive-susceptible in m(s) females result in progeny with highly biased sex ratios, wherein only approximate to14.7% females are produced. We discuss the potential for identifying M-D candidate genes based on comparisons with the well-described Drosophila melanogaster segregation distorter (SD) meiotic drive system and considerations for release of transgenic Ae. aegypti into natural populations where M-D and insensitive m(i) alleles are likely segregating.
Sex chromosome meiotic drive
4332Jaenike, J, Annual Review of Ecology and Systematics, 32:25-49. 2001-01-10 00:00:00.
Sex chromosome drive refers to the unequal transmission of X and Y chromosomes from individuals of the heterogametic sex, resulting in biased sex ratios among progeny and within populations, The presence of driving sex chromosomes can reduce mean fitness within a population, bring about intragenomic conflict between the X chromosome, the Y, and the autosomes, and alter the intensity or mode of sexual selection within species. Sex chromosome drive, or its genetic equivalent, is known in plants, mammals. and flies. Many species harboring driving X chromosomes have evolved Y-linked and autosomal suppressors of drive. If a drive polymorphism is not stable, then driving chromosomes may spread to fixation and cause the extinction of a species. Certain characteristics of species, such as population density and female mating rate, may affect the probability of fixation of driving chromosomes. Thus, sex chromosome drive could be an agent of species-level selection.
An unusual sex-determination system in South American field mice (genus Akodon): The role of mutation, selection, and meiotic drive in maintaining XY females
4330Hoekstra, HEH, J. M., Evolution, 55:190-197. 2001-01-08 00:00:00.
The mechanism of sex determination in mammals appears highly conserved: the presence of a Y chromosome triggers the male developmental pathway, whereas the absence of a Y chromosome results in a default female phenotype. However, if the Y chromosome fails to initiate the male pathway (referred to as Y*), XY* females can result, as is the case in several species of South American field mice (genus Akodon). The breeding genetics in this system inherently select against the Y* chromosome such that the frequency of XY* females should decrease rapidly to very low frequencies. However, in natural populations of Akodon, XY* females persist at substantial frequencies; for example, 10% of females are XY* in A. azarae and 30% in A. boliviensis. We develop a mathematical model that considers the potential roles of three evolutionary forces in maintaining XY* females: Y-to-Y* chromosome transitions (mu ration), chromosome segregation distortion (meiotic drive), and differential fecundity (selection). We then test the predictions of our model using data from breeding colonies of A. azarae. We conclude that any single force is inadequate to maintain XY* females. However, a combination of segregation bias of the male and female Y chromosomes during spermatogenesis/oogenesis and increased fecundity in XY* females could account for the observed frequencies of XY* females.
How common are meiotically driving sex chromosomes in insects?
4357Jiggins, FMH, G. D. D.; Majerus, M. E. N., American Naturalist, 154:481-483. 1999-01-15 00:00:00.
In summary, we argue that the hypothesis that sex chromosome; meiotic drive is common within the insects is in; fact not proved. We feel that, although it is unlikely that; it will be found exclusively in the Diptera, there is a case; to be made that the Diptera are a hot spot for the occurrence; of sex chromosome meiotic drive. Further research; is clearly necessary to clarify this point. If the Diptera; are found to be different, then we must ask why this; is so. Meiotic drive often involves the destruction of gametes; that do not bear the drive allele causing a reduction; in the number of functional gametes. This may mean that; meiotically driving sex chromosomes are unlikely to spread; in female heterogametic taxa such as the Lepidoptera because; a reduction in the number of eggs is more costly; than a reduction in the number of sperm. Among male; heterogametic taxa, it is unclear what could make Dipteran; meiosis special.
Selected lines of Aedes aegypti with persistently distorted sex ratios
4386OwusuDaaku, KOW, R. J.; Butler, R. D., Heredity, 79:388-393. 1997-01-04 00:00:00.
A breeding scheme to isolate X chromosomes sensitive to drive by the T8 (Trinidad) Y chromosome of Aedes aegypti (the MD haplotype) is reported. Crosses with an Australian strain Th.I (Thursday Island) revealed not only sensitive and resistant X chromosomes but also some with the capacity to drive against the T8 Y chromosome. Four strains were created in which sex ratio was male-distorted (28-36 per cent female) for 10 generations, with no regression towards sexual parity. The proportion of females varied significantly between generations in each of the four strains. Further selection produced strains with normal sex ratios, capable of generating fewer than 15 per cent female on outcrossing to T8 males.
Sex-ratio distortion caused by meiotic drive in mosquitos
4458Wood, RJN, M. E., American Naturalist, 137:379-391. 1991-01-16 00:00:00.
Meiotic-drive genes have been described in two species of mosquito, Aedes aegypti and Culex quinquefasciatus. In both species, a Y (M)-linked gene causes a change in sex ratio in favor of males. More is known about the Distorter gene (D) in A. aegypti, but the gene in C. quinquefasciatus appears to be similar. D is located on the right arm of the sex chromosome, is marked with the intercalary Giemsa C-band when present, and is linked closely to the sex locus or region. D undergoes meiotic drive only when in coupling with M, the male-determining gene, which does not recombine with the centromere. Sensitivity to the MD haplotype is controlled at m, the female-determining gene. Therefore, m is considered to be the responder. The m haplotype is polymorphic for sensitivity to MD (m(r1), m(r2), m(s1)-m(s6)). Sensitivity is influenced, in some strains, by a second sex-linked gene t (tolerance to Distorter). Another sex-linked gene, A, enhances the effect of D. Meiotic drive is associated with breaks on the sex chromosomes. First seen at diplotene, mainly at four discrete positions, 90% of these breaks occur on the X (m) chromosome. They usually appear on a chiasmic arm of the bivalent, with the result that most acentric fragments remain attached to the unbroken homologue by a chiasma. Examination of developing spermatozoa in Distorter males reveals extreme sperm depletion, a high degree of abnormality (e.g., multiple axonemes), and an increased DNA content up to the 4C level. Surprisingly, however, the effective fertility of these males is hardly reduced. Evidently, spermatozoa are produced in nondistorter males in vast excess. The Distorter gene has been found in populations from Africa, America, Australia, and Sri Lanka. Resistance to it is much more widespread. The presence of natural resistance argues against the use of D for population control, but its effect has been shown to be enhanced in the presence of certain translocations and the A gene, causing it to become effective in field cage trials, even in the presence of some resistance. There is also experimental support for using D to bring about changes in populations ("population replacement").
Segregation distorters
4451Lyttle, TW, Annual Review of Genetics, 25:511-557. 1991-01-09 00:00:00.
Segregation distorters are genetic elements that exhibit the phenomenon of meiotic drive; that is, the mechanics of the meiotic divisions cause one member of a pair of heterozygous alleles or heteromorphic chromosomes to be transmitted to progeny in excess of the expected Mendelian proportion of 50% ( 1 34 , 1 36). In this review, we refer to these as genic or chromosomal drive, respectively. Genic meiotic drive is initially limited in its impact to the population dynamics of the drive locus itself and those loci fortuitiously in close linkage. Alleles at these latter loci may enjoy indirect drive through genetic hitchhiking, leading eventually to the establishment of drive haplotypes (64). The haplotype may be extended by incorporating chromosome rearrangements that reduce recombination and promote further linkage disequilibrium between the drive locus and more distant modifier loci ( 1 04 , 1 28, 1 64). In the extreme , the haplotype becomes coextensive with the chromosome, leading to a form of chromosomal meiotic drive. For a parent heterozygous for either type of drive system, the statistic k is used to denote the proportion of progeny (and by inference, successful gametes) that carry the allele or chromosome exhibiting segregation distortion. Thus , k can vary from 0 . 5 (Mendelian segregation segregation) to 1 .0 (complete segregation distortion with only one gamete class recovered in the progeny) .
Genetics-driving genes and chromosomes
4463Charlesworth, B, Nature, 332:394-395. 1988-01-21 00:00:00.
Thereare several genetic and chromosomal systems in which Mendel's first law - the equal probability of transmission of maternal and paternal alternative alleles or homologues - is violated. This phenomenon was named 'meiotic drive' in 1957 by Sandler and Novitski, who drew attention to the fact that it operates as an evolutionary force which can cause an increase in the population frequency of the allele or chromosome which is favoured in transmission, even if it confers a disadvantage on its carriers in terms of fitness at the level of the individual
Thte genetic basis of resistance and sensitivity to the meiotic drive gene D in the mosquito Aedes aegypti L.
4469Wood, RJO, N. A., Genetica, 72:69-79. 1987-01-07 00:00:00.
A study has been made on the genetic basis of meiotic drive at the Distorter (D) locus which, in coupling with the male-determining gene (or region) M on the Y chromosome, causes production of excess male progeny. Its effect is regulated by the sensitivity/resistance of the X chromosome. This study demonstrates that there are two major loci controlling resistance/sensitivity to MD: (1) the m gene (or region) on the X chromosome (allelic with M) which may be either m R or m S (resistant or sensitive), (2) the t (tolerance) gene (or genes) which recombines with m and, if present, largely counteracts the effect of m S . There is also evidence that MD itself is capable of limited adaptation.; ; The conclusions were derived from using MD males of the T30 or ACCRA strains (from Trinidad and Ghana respectively). The work involved the use of the CHIPEI and RED strains with sensitive X chromosomes, the latter also carrying the t (tolerance) gene which is linked to re (red eye) and m (the sex-determining locus or region) but recombines with both. The implications of these findings for using MD as a method of population control are discussed.
Meiotic drive in the sex-chromosome system of the varying lemming, Dicrostonyx torquatus Pall (Rodentia, Microtinae)
4465Gileva, EA, Heredity, 59:383-389. 1987-01-03 00:00:00.
In the varying lemming, numerous fertile XY females occur regularly due to the X-linked mutation (X*). Their frequency both in natural populations and laboratory colonies turned out to be about twice higher than that expected under random segregation of heterochromosomes in both sexes. It has been shown in experiments that an excess of XY females resulted from a preferential segregation of the Y chromosome in males. Segregation distortion is not produced by selective embryonal mortality. Meiotic drive of the Y chromosome also causes a significant decrease of sex ratio. Although in the varying lemming meiotic drive is rather weak (the segregation ratio of the Y being 0·54–0·59), it seems to contribute essentially to the evolutionary spread and the maintenance of the X* mutation in populations. The example of Dicrostonyx and probably of other microtines also demonstrates the possible role of meiotic drive in the regulation of the population sex ratio in mammals.
A theoretical-analysis of the effects of sex-chromosome aneuploidy on X-chromosome and Y-chromosome meiotic drive
4476Lyttle, TW, Evolution, 36:822-831. 1982-01-14 00:00:00.
Extra sex chromosomes are normally detrimental to the individual carrying them. In XY (or WZ) sex determining systems, an extra X chromosome in the homogametic sex generates enough X-autosome imbalance to usually cause inviability, or at least sterility. On the oth- er hand, extra Y chromosomes are some- times tolerated, although in mammals and other higher organisms where the Y is ac- tively involved in sexual development, XXY individuals are generally sterile. In Drosophila and perhaps other inverte- brates where the Y is largely genetically inert, a single extra Y may be permitted in both sexes, while two extra copies is only fertile in XXYY females (Cooper, 1956), if at all.
Experimental population-genetics of meiotic drive systems .3: Neutralization of sex-ratio distortion in Drosophila through sex-chromosome aneuploidy
4477Lyttle, TW, Genetics, 98:317-334. 1981-01-15 00:00:00.
Laboratory populations of Drosophila melanogaster were challenged by; pseudo-Y drive, which mimics true Y-chromosome meiotic drive through the; incorporation of Segregation Distorter (SD) in a T(Y;2) complex. This causes; extreme sex-ratio distrotion and can ultimately lead to population extinction.; Populations normally respond by the gradual accumulation of drive suppressors,; and this reduction in strength of distortion allows the sex ratio to move; closer to the optimal value of 1:l. One population monitored, however, was; rapidly able to neutralize the effects of sex-ratio distortion by the accumulation; of sex-chromosome aneuploids (XXY, XYY) . This apparently occurs because; XX-bearing eggs, produced in relatively high numbers (-4%) by XXY; genotypes, become the main population source of females under strong Ychromosome; drive. Computer simulation for a discrete generation model incorporating; random mating with differences in fitness and segregation permits; several predictions that can be compared to the data. First, sex-chromosome; aneuploids should rapidly attain equilibrium, while stabilizing the population; at -60% males. This sex ratio should be roughly independent of the strength; of the meiotic drive. Moreover, conditions favoring the accumulation of drive; suppressors (e.g., weak distortion, slow population extinction) are insufficient; for maintaining aneuploidy, while conditions favoring aneuploidy (e.g., strong; distortion, low production of females) lead to population extinction before drive; suppressors can accumulate. Thus, the different mechanisms for neutralizing; sex-ratio distortion are complementary. In addition, Y drive and sex-chromosome; aneuploidy are potentially co-adaptive, since under some conditions; neither will survive alone. Finally, these results suggest the possibility that; genetic variants promoting sex-chromosome nondisjunction may have a selective; advantage in natural populations faced with sex-ratio distortion.
Experimental population-genetics of meiotic drive systems .1: Pseudo-Y chromosomal drive as a means of eliminating cage populations of Drosophila melanogaster
4487Lyttle, TW, Genetics, 86:413-445. 1977-01-05 00:00:00.
The experimental population genetics of Y-chromosome drive in Drosophila; melanogasier is approximated by studying the behavior of T(Y;S),SD lines.; These exhibit “pseudo-Y” drive through the effective coupling of the Y chromosome; to the second chromosome meiotic drive locus, Segregation distorter; (SD). T(Y;S),SD males consequently produce only male offspring. When; such lines are allowed to compete against structurally normal SD+ flies in; population cages, T(Y;S),SD males increase in frequency according to the; dynamics of a simple haploid selection model until the cage population is; eliminated as a result of a deficiency in the number of adult females. Cage; population extinction generally occurs within about seven generatiomSeveral; conclusions can be drawn from these competition cage studies:; (1) Fitness estimates for the T(Y;Z),SD lines (relative to SD+) are generally; in the range of 2-4, and these values are corroborated by; independent estimates derived from studies of migration-selection; equilibrium.; (2) Fitness estimates are unaffected by cage replication, sample time, or; the starting frequency of T(Y;Z),SD males, indicating that data from; diverse cages can be legitimately pooled to give an overall fitness; estimate.; (3) Partitioning of the T(Y;S),SD fitnesses into components of viability,; fertility, and frequency of alternate segregation (Y + SD from; X+SD+) suggests that most of the T(Y;S),SD advantage derives; from the latter two components. Improvements in the system might; involve increasing both the viability and the alternate segregation to; increase the total fitness.; While pseudo-Y drive operates quite effectively against laboratory stocks,; it is less successful in eliminating wild-type populations which are already; segregating for suppressors of SD action. This observation suggests that further
Between family variation in sex-ratio in Trinidad (T-30) strain of Aedes-aegypti (L) indicating differences in sensitivity to meiotic drive gene MD
4494Wood, RJ, Genetica, 46:345-361. 1976-01-12 00:00:00.
Sex ratio in the Trinidad (T-30) strain of Aedes aegypti has remained constant at around 43%? during seventeen years of laboratory culture. The divergence from 50% is due to meiotic drive by the MD gene on the Y chromosome. The driving Y chromosome gives a much more distorted sex ratio (mean = 5.7%?) when coupled with the highly sensitive X chromosomes from strain 64. This was demonstrated in all of 98 families tested, indicating that all or most of the Y chromosomes in T-30 carry the MD gene. Consequently the low level of sex ratio distortion in T-30 must be due to resistance to MD.; ; Crosses made within T-30 demonstrated wide differences in sex ratio between families, depending on the sensitivity of the male parent's X chromosome to MD. However, sex ratios were not continuously variable but fell within fairly discrete categories. Thus, X chromosomes could be classified according to the modal sex ratios associated with them: ms3 (12.5%?), ms2 (32.5%?), ms1 (40%?), mr1 (47.5%?) mr2 (57.5%?).; ; The different sex ratio categories were more discrete in the families of sib matings than from random matings, suggesting the possibility of background modification of what is essentially a balanced polymorphism. Evidence is presented suggesting that the polymorphism could be due to interaction at two loci. A further X variant, ms4 (<10%?) characterised strain 64 but was absent from T-30.; ; A comparison of fertility between the different sex ratio categories in T-30 established that sex ratio distortion was not caused by differential mortality after fertilisation.
Extraordinary sex ratios
6186W. D. Hamilton, Science, 156:477-488. 1967-04-03 19:10:19.
The two sexes are usually produced in approximately equal numbers. Fisher (1) was the first to explain why, under natural selection, this should be so, irrespective of the particular mechanism of sex determination. His rather tersely expressed argument has been clarified by subsequent writers (2) and seems to be widely accepted. In bare outline, the factor of parental care being ignored, it may be given as follows: 1) Suppose male births are less common than female. 2) A newborn male then has better mating prospects than a newborn female, and therefore can expect to have more offspring. 3) Therefore parents genetically disposed to produce males tend to have more than average numbers of grandchildren born to them. 4) Therefore the genes for male-producing tendencies spread, and male births become commoner. 5) As the 1:1 sex ratio is approached, the advantage associated with producing males dies away. 6) The same reasoning holds if females are substituted for males throughout. Therefore 1:1 is the equilibrium ratio.
Genetic distortion of sex ratio in a mosquito Aedes aegypti
4505Hickey, WAC, G. B., Genetics, 53:1177-1196. 1966-01-03 00:00:00.
CRAIG, HICKEY and VANDEHEY (1960) reported that a hereditary factor transmitted by males was responsible for high male ratios in A. aegypti. This phenomenon was designated as male-producing or MP. Males from high maleproducing families produced a high proportion of males in their own progeny, regardless of the type of female to which they were crossed. This condition was not due to selective mortality, at least in postgametic stages. In 1960, nothing was known about the sex-determining mechanism in A. aegypti. In addition, the male-producing lines available for study were highly variable in expression. These factors hampered more precise analysis of the mechanism of inheritance of MP. The present work was initiated because new crosses with different strains gave more pronounced and predictable distortion of sex ratios. Earlier strains gave about 15 to 30% female, whereas present lines produce about 0 to 15% female. This paper presents an analysis of the mode of inheritance of MP. In addition, data suggesting the mechanism of action are included. Separate reports will be published elsewhere on ( 1 ) the distribution and behavior of MP in experimental populations and (2) the effect of environment on expression of MP. A more detailed account of some of this work is given by HICKEY (1965a, b). Nomenclature used ih these preliminary reports is superseded by that in the present work.
Inherited male-producing factor in Aedes aegypti
6096G. B. Craig, W. A. Hickey and R. C. Vandehey, Science, 132:1887-1889. 1960-12-23 14:59:02.
An inherited factor causes a predominance of males in certain strains and in progeny of single pairs of Aedes aegypti L. This factor appears to be transmitted only by males and is not due to differential mortality, at least in postgametic stages. Mass release of male-producing males might be used in control operations.
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