Scholarly Literature

This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives).  The latest are shown here.
Disclaimer>

A synthetic sex ratio distortion system for the control of the human malaria mosquito

4140
Galizi, RD, L. A.; Menichelli, M.; Bernardini, F.; Deredec, A.; Burt, A.; Stoddard, B. L.; Windbichler, N.; Crisanti, A.,  Nature Communications,  5:3977. 2014-01-18 00:00:00.
It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action of naturally occurring sex distorters and the prevalence of co-evolving suppressors has hampered their use for control. Here we generate a synthetic sex distortion system by exploiting the specificity of the homing endonuclease I-PpoI, which is able to selectively cleave ribosomal gene sequences of the malaria vector Anopheles gambiae that are located exclusively on the mosquito's X chromosome. We combine structure-based protein engineering and molecular genetics to restrict the activity of the potentially toxic endonuclease to spermatogenesis. Shredding of the paternal X chromosome prevents it from being transmitted to the next generation, resulting in fully fertile mosquito strains that produce >95% male offspring. We demonstrate that distorter male mosquitoes can efficiently suppress caged wild-type mosquito populations, providing the foundation for a new class of genetic vector control strategies.

Biased transmission of sex chromosomes in the aphid Myzus persicae is not associated with reproductive mode

4160
Wilson, ACCD, R. N.; Vorburger, C.,  PLOS One,  9:1-12. 2014-01-18 00:00:00.
Commonly, a single aphid species exhibits a wide range of reproductive strategies including cyclical parthenogenesis and obligate parthenogenesis. Sex determination in aphids is chromosomal; females have two X chromosomes, while males have one. X chromosome elimination at male production is generally random, resulting in equal representation of both X chromosomes in sons. However, two studies have demonstrated deviations from randomness in some lineages. One hypothesis to account for such deviations is that recessive deleterious mutations accumulate during bouts of asexual reproduction and affect male viability, resulting in overrepresentation of males with the least deleterious of the two maternal X chromosomes. This hypothesis results in a testable prediction: X chromosome transmission bias will increase with time spent in the asexual phase and should therefore be most extreme in the least sexual aphid life cycle class. Here we test this prediction in Myzus persicae. We used multiple heterozygous X-linked microsatellite markers to screen 1085 males from 95 lines of known life cycle. We found significant deviations from equal representation of X chromosomes in 15 lines; however, these lines included representatives of all life cycles. Our results are inconsistent with the hypothesis that deviations from randomness are attributable to mutation accumulation.

Concerning RNA-guided gene drives for the alteration of wild populations

4139
Esvelt, KMS, Andrea L.; Catteruccia, Flaminia; Church, George M.,  eLife,  3:e03401. 2014-01-17 00:00:00.
Gene drives may be capable of addressing ecological problems by altering entire; populations of wild organisms, but their use has remained largely theoretical due to technical; constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR; nuclease Cas9 to serve as a general method for spreading altered traits through wild populations; over many generations. We detail likely capabilities, discuss limitations, and provide novel; precautionary strategies to control the spread of gene drives and reverse genomic changes. The; ability to edit populations of sexual species would offer substantial benefits to humanity and the; environment. For example, RNA-guided gene drives could potentially prevent the spread of; disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds,; and control damaging invasive species. However, the possibility of unwanted ecological effects and; near-certainty of spread across political borders demand careful assessment of each potential; application. We call for thoughtful, inclusive, and well-informed public discussions to explore the; responsible use of this currently theoretical technology.

Sex-ratio meiotic drive and interspecific competition

4159
Unckless, 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.

Genetic control of invasive fish: technological options and its role in integrated pest management

4158
Thresher, REH, K.; Bax, N. J.; Teem, J.; Benfey, T. J.; Gould, F.,  Biological Invasions,  16:1201-1216. 2014-01-16 00:00:00.
Genetic options for the control of invasive fishes were recently reviewed and synthesized at a 2010 international symposium, held in Minneapolis/St. Paul, MN, USA. The only option currently available "off-the-shelf'' is triploidy, which can be used to produce sterile males for a release program analogous to those widely and successfully used for biological control of insect pests. However, the Trojan Y and several recombinant options that heritably distort pest population sex ratios are technologically feasible, are at or are close to proof-of-concept stage and are potentially much more effective than sterile male release programs. All genetic options at this stage require prolonged stocking programs to be effective, though gene drive systems are a potential for recombinant approaches. They are also likely to differ in their current degree of social acceptability, with chromosomal approaches (triploidy and Trojan Y) likely to be the most readily acceptable to the public and least likely to require changes in legislative or policy settings to be implemented. Modelling also suggests that the efficacy of any of these genetic techniques is enhanced by, and in turn non-additively enhance, conventional methods of pest fish control.

Male eyespan size is associated with meiotic drive in wild stalk-eyed flies (Teleopsis dalmanni)

4138
Cotton, AJF, M.; Cotton, S.; Pomiankowski, A.,  Heredity,  112:363-369. 2014-01-16 00:00:00.
This study provides the first direct evidence from wild populations of stalk-eyed flies to support the hypothesis that male eyespan is a signal of meiotic drive. Several stalk-eyed fly species are known to exhibit X-linked meiotic drive. A recent quantitative trait locus analysis in Teleopsis dalmanni found a potential link between variation in male eyespan, a sexually selected ornamental trait, and the presence of meiotic drive. This was based on laboratory populations subject to artificial selection for male eyespan. In this study, we examined the association between microsatellite markers and levels of sex ratio bias (meiotic drive) in 12 wild T. dalmanni populations. We collected two data sets: (a) brood sex ratios of wild-caught males mated to standard laboratory females and (b) variation in a range of phenotypic traits associated with reproductive success of wild-caught males and females. In each case, we typed individuals for eight X-linked microsatellite markers, including several that previously were shown to be associated with male eyespan and meiotic drive. We found that one microsatellite marker was very strongly associated with meiotic drive, whereas a second showed a weaker association. We also found that, using both independent data sets, meiotic drive was strongly associated with male eyespan, with smaller eyespan males being associated with more female-biased broods. These results suggest that mate preference for exaggerated male eyespan allows females to avoid mating with males carrying the meiotic drive gene and is thus a potential mechanism for the maintenance and evolution of female mate preference.

A selfish gene chastened: Tribolium castaneum Medea M (4) is silenced by a complementary gene

4157
Thomson, MS,  Genetica,  142:161-167. 2014-01-15 00:00:00.
Maternal-effect dominant embryonic arrest (Medea) of Tribolium castaneum are autosomal factors that act maternally to cause the death of any progeny that do not inherit them. This selfish behavior is thought to result from a maternally expressed poison and zygotically expressed antidote. Medea factors and the hybrid incompatibility factor, H, have a negative interaction consistent with complementary genes of the Dobzhansky-Muller model for post-zygotic isolation. This negative interaction may result from H suppression of Medea zygotic antidote, leaving zygotes incompletely protected from maternal poison. I report here a test of the hypothesis that H also suppresses the Medea maternal poison. Viable F-1 females were generated from a cross of Medea M (4) strain males to H strain females. These females, heterozygous for both M (4) and H, failed to express M (4) maternal lethal activity when crossed to their male sibs. Transmission of non-M (4) homologues from these females was confirmed using a dominant transgenic enhanced green fluorescent protein eye color marker, tightly linked in cis to M (4) . M (4) beetles, lacking H, were selected from the F-2 population. Female descendants of these clearly expressed M (4) maternal lethal activity, indicating restoration of this activity after H was segregated away. I conclude that H, or a factor tightly linked to H, suppresses Medea M (4) maternal poison.

Centromere strength provides the cell biological basis for meiotic drive and karyotype evolution in mice

4137
Chmatal, LG, S. I.; Mitsainas, G. P.; Martinez-Vargas, J.; Ventura, J.; Searle, J. B.; Schultz, R. M.; Lampson, M. A.,  Current Biology,  24:2295-2300. 2014-01-15 00:00:00.
Mammalian karyotypes (number and structure of chromosomes) can vary dramatically over short evolutionary time frames [1-3]. There are examples of massive karyotype conversion, from mostly telocentric (centromere terminal) to mostly metacentric (centromere internal), in 102-10 s years [4, 5]. These changes typically reflect rapid fixation of Robertsonian (Rb) fusions, a common chromosomal rearrangement that joins two telocentric chromosomes at their centromeres to create one metacentric [5]. Fixation of Rb fusions can be explained by meiotic drive: biased chromosome segregation during female meiosis in violation of Mendel's first law [3, 6, 7]. However, there is no mechanistic explanation of why fusions would preferentially segregate to the egg in some populations, leading to fixation and karyotype change, while other populations preferentially eliminate the fusions and maintain a telocentric karyotype. Here we show, using both laboratory models and wild mice, that differences in centromere strength predict the direction of drive. Stronger centromeres, manifested by increased kinetochore protein levels and altered interactions with spindle microtubules, are preferentially retained in the egg. We find that fusions preferentially segregate to the polar body in laboratory mouse strains when the fusion centromeres are weaker than those of telocentrics. Conversely, fusion centromeres are stronger relative to telocentrics in natural house mouse populations that have changed karyotype by accumulating metacentric fusions. Our findings suggest that natural variation in centromere strength explains how the direction of drive can switch between populations. They also provide a cell biological basis of centromere drive and karyotype evolution.

An X-linked sex ratio distorter in Drosophila simulans that kills or incapacitates both noncarrier sperm and sons

4156
Rice, WR,  G3-Genes Genomes Genetics,  4:1837-1848. 2014-01-14 00:00:00.
Genomic conflict occurs when a genomic component gains a reproductive advantage at the expense of the organism as a whole. X-linked segregation distorters kill or incapacitate Y-bearing sperm, thereby gaining a transmission advantage but also reducing male fertility and generating a female-biased sex ratio. When some damaged, Y-bearing sperm survive and fertilize eggs, then the segregation distortion phenotype could be expanded by harming or killing sons in the next generation. X-linked son-killers are predicted by theory to be favored by natural selection and evolve when brothers and sisters compete for shared limiting resources and/or when brothers reduce the inclusive fitness of their sisters via sib-mating-a phenomenon called SA-zygotic drive. Here I develop and use a process-of-elimination screen to show that an unclassified X-linked sex ratio distorter (skew) in Drosophila simulans kills or incapacitates noncarrier sperm and also kills a substantial proportion of sons, i.e., it has both a segregation distortion and a SA-zygotic drive phenotype. There are three unique X-linked segregation distorters known to occur in D. simulans named Winters, Durham, and Paris. Autosomal-dominant suppressors of Winters (Nmy) and Durham (Tmy) failed to suppress skew. A Y-linked suppressor of Paris, however, did suppress skew, and a recombination test failed to detect recombinants between these two sex ratio distorters, indicating that they are tightly linked and plausibly identical or allelic. Son-killing may be an important yet unrecognized component of other X-linked segregation distorters.

Heritable strategies for controlling insect vectors of disease

4136
Burt, A,  Philosophical Transactions of the Royal Society B-Biological Sciences,  369:20130432. 2014-01-14 00:00:00.
Mosquito-borne diseases are causing a substantial burden of mortality, morbidity and economic loss in many parts of the world, despite current control efforts, and new complementary approaches to controlling these diseases are needed. One promising class of new interventions under development involves the heritable modification of the mosquito by insertion of novel genes into the nucleus or of Wolbachia endosymbionts into the cytoplasm. Once released into a target population, these modifications can act to reduce one or more components of the mosquito population's vectorial capacity (e. g. the number of female mosquitoes, their longevity or their ability to support development and transmission of the pathogen). Some of the modifications under development are designed to be self-limiting, in that they will tend to disappear over time in the absence of recurrent releases (and hence are similar to the sterile insect technique, SIT), whereas other modifications are designed to be self-sustaining, spreading through populations even after releases stop (and hence are similar to traditional biological control). Several successful field trials have now been performed with Aedes mosquitoes, and such trials are helping to define the appropriate developmental pathway for this new class of intervention.

Meiotic drive impacts expression and evolution of X-linked genes in stalk-eyed flies

4155
Reinhardt, JAB, C. L.; Paczolt, K. A.; Johns, P. M.; Baker, R. H.; Wilkinson, G. S.,  PLOS Genetics,  10:e1004362. 2014-01-13 00:00:00.
Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (X-SR) or a standard X chromosome (X-ST), and found hundreds of these, the majority of which are X-linked. Drive-associated transcripts show increased levels of sequence divergence (dN/dS) compared to a control set, and are predominantly expressed either in testes or in the gonads of both sexes. Finally, we confirmed that X-SR and X-ST are highly divergent by estimating sequence differentiation between the RNAseq pools. We found that X-linked transcripts were often strongly differentiated (whereas most autosomal transcripts were not), supporting the presence of a relatively large region of recombination suppression on X-SR presumably caused by one or more inversions. We have identified a group of genes that are good candidates for further study into the causes and consequences of sex-chromosome drive, and demonstrated that meiotic drive has had a profound effect on sequence evolution and gene expression of X-linked genes in this species.

Regulatory experience and challenges for the release of GM insects

4135
Beech, C,  Journal Fur Verbraucherschutz Und Lebensmittelsicherheit-Journal of Consumer Protection and Food Safety,  9:S71-S76. 2014-01-13 00:00:00.
Genetically modified (GM) insects are a potentially valuable new tool for the biological control of insect pests of humans, animals and plants. Considerable progress has been made recently in transfer of GM insects from the laboratory to release and evaluation in the environment. As with other new genetic technologies, regulatory agencies have often found it challenging to determine the regulatory regime under which they should be evaluated, and have either adapted existing regulatory frameworks or adopted new ones. No country has legislation specifically for GM insects. However, irrespective of the regulatory regime under which they are evaluated, the purpose of their regulation remains the same; to protect human health and the environment. Consequently there are evaluation themes common to their regulatory scrutiny, which are elucidated here. There have also been some challenges and issues encountered during the risk evaluation for field release of GM insects, and this paper will highlight some of these to assist others when considering policy, regulation and assessment of GM insects. Useful regulatory and policy precedents also exist from the regulation of biological control agents and the global protection of plants from pests under the International Standards for Phytosanitary Measures (ISPM) framework. Where countries do not have existing regulations, these evaluation instruments could have the potential to be adapted to form a suitable framework for the assessment of risk for GM insects. Finally, some considerations for future policy and regulation in this area are discussed.

Analysis of segregation distortion and its relationship to hybrid barriers in rice

4154
Reflinur, K, B.; Jang, S. M.; Chu, S. H.; Bordiya, Y.; Akter, M. B.; Lee, J.; Chin, J. H.; Koh, H. J.,  Rice,  7:3. 2014-01-12 00:00:00.
Segregation distortion (SD) is a frequently observed occurrence in mapping populations generated from crosses involving divergent genotypes. In the present study, ten genetic linkage maps constructed from reciprocal F-2 and BC1F1 mapping populations derived from the parents Dasanbyeo (indica) and Ilpumbyeo (japonica) were used to identify the distribution, effect, and magnitude of the genetic factors underlying the mechanisms of SD between the two subspecies. ResultsSD loci detected in the present study were affected by male function, female function, and zygotic selection. The most pronounced SD loci were mapped to chromosome 3 (transmitted through male gametes), chromosome 5 (transmitted through male gametes), and chromosome 6 (transmitted through female gametes). The level of SD in BC1F1 populations which defined by chi-square value independence multiple tests was relatively low in comparison to F-2 populations. Dasanbyeo alleles were transmitted at a higher frequency in both F-2 and BC1F1 populations, suggesting that indica alleles are strongly favored in inter-subspecific crosses in rice. SD loci in the present study corresponded to previously reported loci for reproductive barriers. In addition, new SD loci were detected on chromosomes 2 and 12. ConclusionThe identification of the distribution of SD and the effect of genetic factors causing SD in genetic mapping populations provides an opportunity to survey the whole genome for new SD loci and their relationships to reproductive barriers. This provides a basis for future research on the elucidation of the genetic mechanisms underlying SD in rice, and will be useful in molecular breeding programs.

Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila: A theoretical exploration of Medea-dependent population suppression

4134
Akbari, OSC, C. H.; Marshall, J. M.; Huang, H. X.; Antoshechkin, I.; Hay, B. A.,  ACS Synthetic Biology,  3:915-928. 2014-01-12 00:00:00.
Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.

Multiple sex chromosomes in the light of female meiotic drive in amniote vertebrates

4153
Pokorna, MA, M.; Kratochvil, L.,  Chromosome Research,  22:35-44. 2014-01-11 00:00:00.
It is notable that the occurrence of multiple sex chromosomes differs significantly between major lineages of amniote vertebrates. In this respect, birds are especially conspicuous, as multiple sex chromosomes have not been observed in this lineage so far. On the other hand, in mammals, multiple sex chromosomes have evolved many times independently. We hypothesize that this contrast can be related to the different involvement of sex-specific sex chromosomes in female meiosis subjected to the female meiotic drive under male versus female heterogamety. Essentially, the male-specific Y chromosome is not involved in female meiosis and is therefore sheltered against the effects of the female meiotic drive affecting the X chromosome and autosomes. Conversely, the Z and W sex chromosomes are both present in female meiosis. Nonrandom segregation of these sex chromosomes as a consequence of their rearrangements connected with the emergence of multiple sex chromosomes would result in a biased sex ratio, which should be penalized by selection. Therefore, the emergence of multiple sex chromosomes should be less constrained in the lineages with male rather than female heterogamety. Our broader phylogenetic comparison across amniotes supports this prediction. We suggest that our results are consistent with the widespread occurrence of female meiotic drive in amniotes.

Meiotic drive influences the outcome of sexually antagonistic selection at a linked locus

4152
Patten, MM,  Journal of Evolutionary Biology,  27:2360-2370. 2014-01-10 00:00:00.
Most meiotic drivers, such as the t-haplotype in Mus and the segregation distorter (SD) in Drosophila, act in a sex-specific manner, gaining a transmission advantage through one sex although suffering only the fitness costs associated with the driver in the other. Their inheritance is thus more likely through one of the two sexes, a property they share with sexually antagonistic alleles. Previous theory has shown that pairs of linked loci segregating for sexually antagonistic alleles are more likely to remain polymorphic and that linkage disequilibrium accrues between them. I probe this similarity between drive and sexual antagonism and examine the evolution of chromosomes experiencing these selection pressures simultaneously. Reminiscent of previous theory, I find that: the opportunity for polymorphism increases for a sexually antagonistic locus that is physically linked to a driving locus; the opportunity for polymorphism at a driving locus also increases when linked to a sexually antagonistic locus; and stable linkage disequilibrium accompanies any polymorphic equilibrium. Additionally, I find that drive at a linked locus favours the fixation of sexually antagonistic alleles that benefit the sex in which drive occurs. Further, I show that under certain conditions reduced recombination between these two loci is selectively favoured. These theoretical results provide clear, testable predictions about the nature of sexually antagonistic variation on driving chromosomes and have implications for the evolution of genomic architecture.

Regulating gene drives

4151
Oye, KAE, K.; Appleton, E.; Catteruccia, F.; Church, G.; Kuiken, T.; Lightfoot, S. B. Y.; McNamara, J.; Smidler, A.; Collins, J. P.,  Science,  345:626-628. 2014-01-09 00:00:00.
Regulatory gaps must be filled before gene drives could be used in the wild

Feasible introgression of an anti-pathogen transgene into an urban mosquito population without using gene-drive

4150
Okamoto, KWR, M. A.; Gould, F.; Lloyd, A. L.,  PLOS Neglected Tropical Diseases,  8:e2827. 2014-01-08 00:00:00.
Introgressing anti-pathogen constructs into wild vector populations could reduce disease transmission. It is generally assumed that such introgression would require linking an anti-pathogen gene with a selfish genetic element or similar technologies. Yet none of the proposed transgenic anti-pathogen gene-drive mechanisms are likely to be implemented as public health measures in the near future. Thus, much attention now focuses instead on transgenic strategies aimed at mosquito population suppression, an approach generally perceived to be practical. By contrast, aiming to replace vector competent mosquito populations with vector incompetent populations by releasing mosquitoes carrying a single anti-pathogen gene without a gene-drive mechanism is widely considered impractical. Methodology/Principal FindingsHere we use Skeeter Buster, a previously published stochastic, spatially explicit model of Aedes aegypti to investigate whether a number of approaches for releasing mosquitoes with only an anti-pathogen construct would be efficient and effective in the tropical city of Iquitos, Peru. To assess the performance of such releases using realistic release numbers, we compare the transient and long-term effects of this strategy with two other genetic control strategies that have been developed in Ae. aegyptirelease of a strain with female-specific lethality, and a strain with both female-specific lethality and an anti-pathogen gene. We find that releasing mosquitoes carrying only an anti-pathogen construct can substantially decrease vector competence of a natural population, even at release ratios well below that required for the two currently feasible alternatives that rely on population reduction. Finally, although current genetic control strategies based on population reduction are compromised by immigration of wild-type mosquitoes, releasing mosquitoes carrying only an anti-pathogen gene is considerably more robust to such immigration. Conclusions/SignificanceContrary to the widely held view that transgenic control programs aimed at population replacement require linking an anti-pathogen gene to selfish genetic elements, we find releasing mosquitoes in numbers much smaller than those considered necessary for transgenic population reduction can result in comparatively rapid and robust population replacement. In light of this non-intuitive result, directing efforts to improve rearing capacity and logistical support for implementing releases, and reducing the fitness costs of existing recombinant technologies, may provide a viable, alternative route to introgressing anti-pathogen transgenes under field conditions.

Transmission distortion affecting human noncrossover but not crossover recombination: A hidden source of meiotic drive

4149
Odenthal-Hesse, LB, I. L.; Veselis, A.; Jeffreys, A. J.; May, C. A.,  PLOS Genetics,  10:e1004106. 2014-01-07 00:00:00.
Author Summary Meiosis is an essential feature of sexual reproduction that maintains chromosome number over generations. This specialised form of cell division creates gametes containing a single copy of each chromosome so that each parent contributes half their genetic information to an offspring. Accurate partitioning first requires intimate association of the two parental copies of each chromosome and concomitant exchange between them. These exchanges consist of both large-scale reciprocal crossovers, essential for correct chromosome segregation, and very localised gene conversion events, or noncrossovers, thought to be involved in correct chromosome pairing. Ordinarily, the reshuffling of genetic variants between generations by recombination will not alter their population frequency only their haplotypic context, with a parent passing on a given variant to 50% of its gametes according to Mendel's law of inheritance. However, by screening for both types of recombinant amongst the sperm DNA of healthy men, we have identified a novel form of biased transmission that is restricted to noncrossovers and favours eventual fixation of one variant over another in the population. This previously undetected source of meiotic drive will not alter recombination propensity but is likely to be a common and potent force acting on the human genome. Meiotic recombination ensures the correct segregation of homologous chromosomes during gamete formation and contributes to DNA diversity through both large-scale reciprocal crossovers and very localised gene conversion events, also known as noncrossovers. Considerable progress has been made in understanding factors such as PRDM9 and SNP variants that influence the initiation of recombination at human hotspots but very little is known about factors acting downstream. To address this, we simultaneously analysed both types of recombinant molecule in sperm DNA at six highly active hotspots, and looked for disparity in the transmission of allelic variants indicative of any cis-acting influences. At two of the hotspots we identified a novel form of biased transmission that was exclusive to the noncrossover class of recombinant, and which presumably arises through differences between crossovers and noncrossovers in heteroduplex formation and biased mismatch repair. This form of biased gene conversion is not predicted to influence hotspot activity as previously noted for SNPs that affect recombination initiation, but does constitute a powerful and previously undetected source of recombination-driven meiotic drive that by extrapolation may affect thousands of recombination hotspots throughout the human genome. Intriguingly, at both of the hotspots described here, this drive favours strong (G/C) over weak (A/T) base pairs as might be predicted from the well-established correlations between high GC content and recombination activity in mammalian genomes.

Evidence for meiotic drive as an explanation for karyotype changes in fishes

4148
Molina, WFM, P. A.; Bertollo, L. A. C.; Bidau, C. J.,  Marine Genomics,  15:29-34. 2014-01-06 00:00:00.
The process of preferential chromosome segregation during meiosis has been suggested to be responsible for the predominance of certain chromosome types in the karyotypes of mammals, birds and insects. We developed an extensive analysis of the fixation of mono- or bibrachial chromosomes in the karyotypes of the large Actinopterygii fish group, a key link in the evolution of terrestrial vertebrates, in order to investigate the generality of meiotic drive in determining karyotypic macrotrends. Unlike mammals, fishes have markedly undergone several types of preferential chromosomal rearrangements throughout evolution. Data from the analyzed orders indicate a prevalence of karyotypes with few (<33%) or many (>66%) acrocentric chromosomes and a low number of karyotypes with balanced numbers of mono- and bi-brachial elements. Parallel trends towards a higher number of karyotypes with prevalence of monobrachial chromosomes occurred in phylogenetically close orders (e.g. Perciformes and Tetraodontiformes, and in the order Mugiliformes) and in clades with prevalence of bibrachial elements (e.g. Characiformes, Gymnotiformes, Siluriformes, and Cypriniformes). Some orders where fewer species were available for study, such as Atheriniformes and Anguilliformes, showed karyotype assemblages where both trends were present. Our results strongly suggest a primary role of meiotic drive in karyotypic evolution as indicated by the accumulation of monobrachial chromosomes in Perciformes and Cypriniformes, or bibrachial chromosomes in Siluriformes and Characiformes. Further examinations of the interaction between life history traits, environmental characteristics, and the fixation of chromosomal rearrangements would be exceedingly valuable.

« First ‹ Previous 1 85 93 94 95 96 97 105 118 Next › Last »