Scholarly Literature
This is an aggregation of scholarly literature from peer-reviewed journals, bioRxiv , medRxiv and arXiv preprint servers focused on natural and engineered selfish genetic elements and genetic biocontrol. New citations are added as they appear. This content is intended for anyone interested in the scholarly literature on gene drive and genetic biocontrol.
Why RIDL is not SIT
26699W. C. Black, L. Alphey and A. A. James, Trends in Parasitology, 27:362-370. 2011-08-01 07:23:46.
History teaches that sterile insect technique (SIT) is a feasible strategy for mosquito population suppression. Female killing (FK) technologies developed later theoretically had greater potential than SIT, but depended upon chromosomal translocations. Unfortunately these were genetically unstable. New transgenic strategies have been misinterpreted as a replacement for SIT. Instead these strategies provide a means to revisit FK. Conditional lethal mutations inserted into mosquito genomes allow for adjustment of the age of mortality, female-specific lethality, bisexual lethality and manipulation of germline-specific gene expression. A recent Aedes aegypti case study demonstrates the viability of one of these new transgenic strategies.
Existence of global attractor for the Trojan Y Chromosome model
11534X. P. Zhao, B. Liu and N. Duan, Electronic Journal of Qualitative Theory of Differential Equations, 2011-07-11 17:09:12.
This paper is concerned with the long time behavior of solution for the equation derived by the Trojan Y Chromosome (TYC) model with spatial spread. Based on the regularity estimates for the semigroups and the classical existence theorem of global attractors, we prove that this equations possesses a global attractor in H-k(Omega)(4) (k >= 0) space.
A Theoretical Strategy for Eradication of Asian Carps Using a Trojan Y Chromosome to Shift the Sex Ratio of the Population
11538J.L. teem and J.B. Gutierrez, Invasive Asian Carps in North America, 74:227-238. 2011-06-01 17:13:22.
The directed extinction of an exotic fish population is proposed using a genetic approach to drastically reduce the ratio of females to males within the population. In the proposed strategy, sex-reversed female fish containing two Y chromosomes (Fyy) are introduced into a normal fish population. The frequencies of each of the four expected genotypes of fish in the simulated population (Fxx, Fyy, Mxy, and Myy) were modeled with a set of coupled ordinary differential equations. The equations take into account birth rate, death rate, and a fixed carrying capacity of the system. Using computer-generated simulations, it was determined that the continuous introduction of a relatively small proportion of Fyy females to the normal population leads to extinction of the exotic fish over time. The proposed eradication strategy is relevant to fish species with an XY sex-determination system that tolerate a YY genotype. Published literature suggests that Asian carps are likely to fulfill these criteria. However, technical barriers associated with sex reversal in Asian carps presently exist and must be overcome before implementation of a YY eradication strategy for Asian carps can be considered in practice. An idealized theoretical model for the eradication of Asian carps is thus presented.
Analysis of the Trojan Y chromosome model for eradication of invasive species in a dendritic riverine system
11532J. B. Gutierrez, M. K. Hurdal, R. D. Parshad and J. L. Teem, Journal of Mathematical Biology, 64:319-340. 2011-03-04 17:07:15.
The use of Trojan Y chromosomes has been proposed as a genetic strategy for the eradication of invasive species. The strategy is particularly relevant to invasive fish species that have XY sex determination system and are amenable to sex-reversal. In this paper we study the dynamics of an invasive fish population occupying a dendritic domain in which Trojan individuals bearing multiple Y chromosomes have been released as a means of eradication. We demonstrate the existence of a bounded absorbing set that represents extinction of the invasive species irrespective of the dendritic configuration. The method of analysis used to obtain global estimates could be applied to other population problems and other geometries.
Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?
12676H. Ranson, R. N’Guessan, J. Lines, N. Moiroux, Z. Nkuni and V. Corbel, Trends in Parasitology, 27:91-98. 2011-02-01 17:44:55.
The use of pyrethroid insecticides in malaria vector control has increased dramatically in the past decade through the scale up of insecticide treated net distribution programmes and indoor residual spraying campaigns. Inevitably, the major malaria vectors have developed resistance to these insecticides and the resistance alleles are spreading at an exceptionally rapid rate throughout Africa. Although substantial progress has been made on understanding the causes of pyrethroid resistance, remarkably few studies have focused on the epidemiological impact of resistance on current malaria control activities. As we move into the malaria eradication era, it is vital that the implications of insecticide resistance are understood and strategies to mitigate these effects are implemented.
Requirements for effective malaria control with homing endonuclease genes
4203Deredec, AG, H. C. J.; Burt, A., Proceedings of the National Academy of Sciences of the United States of America, 108:e874-e880. 2011-01-21 00:00:00.
Malaria continues to impose a substantial burden on human health. We have previously proposed that biological approaches to control the mosquito vector of disease could be developed using homing endonuclease genes (HEGs), a class of selfish or parasitic gene that exists naturally in many microbes. Recent lab studies have demonstrated that HEGs can function in mosquitoes. We constructed and analyzed a model of mosquito population genetics and malaria epidemiology to determine how well HEGs need to function in order to have a significant effect on the burden of disease. Our model, combined with currently available data, indicates that populations of Anopheles gambiae could be eliminated by releasing 2-3 HEGs targeting female fertility genes, or a driving-Y chromosome that is transmitted to 75-96% of progeny. Combinations of fertility-targeting HEGs and Y drive may also be effective. It is possible to eliminate the disease without eliminating the vector, but the parameter space producing this outcome appears to be small. HEGs causing a quantitative reduction in adult survival can be more effective than those targeting female fertility, but the selection coefficients that need to be imposed are still large, unless many HEGs are to be released. Simulations show that HEG-based strategies can be effective over socially relevant time frames. Important limiting assumptions of the models are that there is only a single vector species, and we model a homogeneous population, not a landscape. Nevertheless, we conclude that HEG-based approaches could have a transformational effect on malaria control efforts.
Reduced polymorphism associated with X chromosome meiotic drive in the stalk-eyed fly Teleopsis dalmanni
4202Christianson, SJB, C. L.; Wilkinson, G. S., PLOS One, 6:e27254. 2011-01-20 00:00:00.
Sex chromosome meiotic drive has been suggested as a cause of several evolutionary genetic phenomena, including genomic conflicts that give rise to reproductive isolation between new species. In this paper we present a population genetic analysis of X chromosome drive in the stalk-eyed fly, Teleopsis dalmanni, to determine how this natural polymorphism influences genetic diversity. We analyzed patterns of DNA sequence variation at two X-linked regions (comprising 1325 bp) approximately 50 cM apart and one autosomal region (comprising 921 bp) for 50 males, half of which were collected in the field from one of two allopatric locations and the other half were derived from lab-reared individuals with known brood sex ratios. These two populations are recently diverged but exhibit partial postzygotic reproductive isolation, i.e. crosses produce sterile hybrid males and fertile females. We find no nucleotide or microsatellite variation on the drive X chromosome, whereas the same individuals show levels of variation at autosomal regions that are similar to field-collected flies. Furthermore, one field-caught individual collected 10 years previously had a nearly identical X haplotype to the drive X, and is over 2% divergent from other haplotypes sampled from the field. These results are consistent with a selective sweep that has removed genetic variation from much of the drive X chromosome. We discuss how this finding may relate to the rapid evolution of postzygotic reproductive isolation that has been documented for these flies.
Insect population control by homing endonuclease-based gene drive: An evaluation in Drosophila melanogaster
4201Chan, YSN, D. A.; Huen, D. S.; Russell, S., Genetics, 188:33-44. 2011-01-19 00:00:00.
Insects play a major role as vectors of human disease as well as causing significant agricultural losses. Harnessing the activity of customized homing endonuclease genes (HEGs) has been proposed as a method for spreading deleterious mutations through populations with a view to controlling disease vectors. Here, we demonstrate the feasibility of this method in Drosophila melanogaster, utilizing the well-characterized HEG, I-SceI. In particular, we show that high rates of homing can be achieved within spermatogonia and in the female germline. We show that homed constructs continue to exhibit HEG activity in the subsequent generation and that the ectopic homing events required for initiating the strategy occur at an acceptable rate. We conclude that the requirements for successful deployment of a HEG-based gene drive strategy can be satisfied in a model dipteran and that there is a reasonable prospect of the method working in other dipterans. In characterizing the system we measured repair outcomes at the spermatogonial, spermatocyte, and spermatid stages of spermatogenesis. We show that homologous recombination is restricted to spermatogonia and that it immediately ceases when they become primary spermatocytes, indicating that the choice of DNA repair pathway in the Drosophila testis can switch abruptly during differentiation.
B Chromosomes and Sex in Animals
4200Camacho, JPMS, M.; Cabrero, J., Sexual Development, 5:155-166. 2011-01-18 00:00:00.
Supernumerary (B) chromosomes are dispensable elements found in many eukaryote genomes in addition to standard (A) chromosomes. In many respects, B chromosomes resemble sex chromosomes, so that a common ancestry for them has frequently been suggested. For instance, B chromosomes in grasshoppers, and other insects, show a pycnotic cycle of condensation-decondensation during meiosis remarkably similar to that of the X chromosome. In some cases, B chromosome size is even very similar to that of the X chromosome. These resemblances have led to suggest the X as the B ancestor in many cases. In addition, sex chromosome origin from B chromosomes has also been suggested. In this article, we review the existing evidence for both evolutionary pathways, as well as sex differences for B frequency at adult and embryo progeny levels, B chromosome effects or B chromosome transmission. In addition, we review cases found in the literature showing sex-ratio distortion associated with B chromosome presence, the most extreme case being the paternal sex ratio (PSR) chromosomes in some Hymenoptera. We finally analyse the possibility of B chromosome regularisation within the host genome and, as a consequence of it, whether B chromosomes can become regular members of the host genome. Copyright (C) 2011 S. Karger AG, Basel
Rapid rise and fall of selfish sex-ratio X Chromosomes in Drosophila simulans: Spatiotemporal analysis of phenotypic and molecular data
4199Bastide, HC, M.; Ogereau, D.; Derome, N.; Hospital, F.; Montchamp-Moreau, C., Molecular Biology and Evolution, 28:2461-2470. 2011-01-17 00:00:00.
Sex-ratio drive, which has been documented in several Drosophila species, is induced by X-linked segregation distorters. Contrary to Mendel's law of independent assortment, the sex-ratio chromosome (X(SR)) is inherited by more than half the offspring of carrier males, resulting in a female-biased sex ratio. This segregation advantage allows X(SR) to spread in populations, even if it is not beneficial for the carriers. In the cosmopolitan species D. simulans, the Paris sex-ratio is caused by recently emerged selfish X(SR) chromosomes. These chromosomes have triggered an intragenomic conflict, and their propagation has been halted over a large area by the evolution of complete drive suppression. Previous molecular population genetics analyses revealed a selective sweep indicating that the invasion of X(SR) chromosomes was very recent in Madagascar (likely less than 100 years ago). Here, we show that X(SR) chromosomes are now declining at this location as well as in Mayotte and Kenya. Drive suppression is complete in the three populations, which display little genetic differentiation and share swept haplotypes, attesting to a common and very recent ancestry of the X(SR) chromosomes. Patterns of DNA sequence variation also indicate a fitness cost of the segmental duplication involved in drive. The data suggest that X(SR) chromosomes started declining first on the African continent, then in Mayotte, and finally in Madagascar and strongly support a scenario of rapid cycling of X chromosomes. Once drive suppression has evolved, standard X(ST) chromosomes locally replace costly X(SR) chromosomes in a few decades.
Stability properties of underdominance in finite subdivided populations
4198Altrock, PMT, A.; Reed, F. A., PLOS Computational Biology, 7:10. 2011-01-16 00:00:00.
In isolated populations underdominance leads to bistable evolutionary dynamics: below a certain mutant allele frequency the wildtype succeeds. Above this point, the potentially underdominant mutant allele fixes. In subdivided populations with gene flow there can be stable states with coexistence of wildtypes and mutants: polymorphism can be maintained because of a migration-selection equilibrium, i.e., selection against rare recent immigrant alleles that tend to be heterozygous. We focus on the stochastic evolutionary dynamics of systems where demographic fluctuations in the coupled populations are the main source of internal noise. We discuss the influence of fitness, migration rate, and the relative sizes of two interacting populations on the mean extinction times of a group of potentially underdominant mutant alleles. We classify realistic initial conditions according to their impact on the stochastic extinction process. Even in small populations, where demographic fluctuations are large, stability properties predicted from deterministic dynamics show remarkable robustness. Fixation of the mutant allele becomes unlikely but the time to its extinction can be long.
A synthetic homing endonuclease-based gene drive system in the human malaria mosquito
4211Windbichler, NM, M.; Papathanos, P. A.; Thyme, S. B.; Li, H.; Ulge, U. Y.; Hovde, B. T.; Baker, D.; Monnat, R. J.; Burt, A.; Crisanti, A., Nature, 473:212-215. 2011-01-09 00:00:00.
Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity(1-3). The development of genetically engineered malaria-resistant mosquitoes has shown, as a proof of principle, the possibility of targeting the mosquito's ability to serve as a disease vector(4-7). The translation of these achievements into control measures requires an effective technology to spread a genetic modification from laboratory mosquitoes to field populations(8). We have suggested previously that homing endonuclease genes (HEGs), a class of simple selfish genetic elements, could be exploited for this purpose(9). Here we demonstrate that a synthetic genetic element, consisting of mosquito regulatory regions(10) and the homing endonuclease gene I-SceI(11-13), can substantially increase its transmission to the progeny in transgenic mosquitoes of the human malaria vector Anopheles gambiae. We show that the I-SceI element is able to invade receptive mosquito cage populations rapidly, validating mathematical models for the transmission dynamics of HEGs. Molecular analyses confirm that expression of I-SceI in the male germline induces high rates of site-specific chromosomal cleavage and gene conversion, which results in the gain of the I-SceI gene, and underlies the observed genetic drive. These findings demonstrate a new mechanism by which genetic control measures can be implemented. Our results also show in principle how sequence-specific genetic drive elements like HEGs could be used to take the step from the genetic engineering of individuals to the genetic engineering of populations.
Selfish genetic elements, genetic conflict, and evolutionary innovation
4210Werren, JH, Proceedings of the National Academy of Sciences of the United States of America, 108:10863-10870. 2011-01-08 00:00:00.
Genomes are vulnerable to selfish genetic elements (SGEs), which enhance their own transmission relative to the rest of an individual's genome but are neutral or harmful to the individual as a whole. As a result, genetic conflict occurs between SGEs and other genetic elements in the genome. There is growing evidence that SGEs, and the resulting genetic conflict, are an important motor for evolutionary change and innovation. In this review, the kinds of SGEs and their evolutionary consequences are described, including how these elements shape basic biological features, such as genome structure and gene regulation, evolution of new genes, origin of new species, and mechanisms of sex determination and development. The dynamics of SGEs are also considered, including possible "evolutionary functions" of SGEs.
Transcript profiling of the meiotic drive phenotype in testis of Aedes aegypti using suppressive subtractive hybridization
4209Shin, DYJ, L. Z.; Lobo, N. F.; Severson, D. W., Journal of Insect Physiology, 57:1220-1226. 2011-01-07 00:00:00.
The meiotic drive gene in Aedes aegypti is tightly linked with the sex determination locus on chromosome 1, and causes highly male-biased sex ratios. We prepared cDNA libraries from testes from the Ae. aegypti 137 strain (driving) and RED strain (non-driving), and used suppressive subtraction hybridization techniques to enrich for 137 testes-specific transcripts. Expressed sequence tags (ESTs) were obtained from a total of 2784 randomly selected clones from the subtracted 137 (subT37) library as well as the primary libraries for each strain (pT37 and pRED). Sequence analysis identified a total of 171 unique genes in the subT37 library and 299 unique genes among the three libraries. The majority of genes enriched in the subT37 library were associated with signal transduction, development, reproduction, metabolic process and cell cycle functions. Further, as observed with meiotic drive systems in Drosophila and mouse, a number of these genes were associated with signaling cascades that involve the Ras superfamily of regulatory small GTPases. Differential expression of several of these genes was verified in Ae. aegypti pupal testes using qRT-PCR. This study increases our understanding of testes gene expression enriched in adult males from the meiotic drive strain as well as insights into the basic testes transcriptome in Ae. aegypti. (C) 2011 Elsevier Ltd. All rights reserved.
A novel sperm-delivered toxin causes late-stage embryo lethality and transmission ratio distortion in C. elegans
4208Seidel, HSA, M.; Li, J. L.; van Oudenaarden, A.; Rockman, M. V.; Kruglyak, L., PLOS Biology, 9:e1001115. 2011-01-06 00:00:00.
The evolutionary fate of an allele ordinarily depends on its contribution to host fitness. Occasionally, however, genetic elements arise that are able to gain a transmission advantage while simultaneously imposing a fitness cost on their hosts. We previously discovered one such element in C. elegans that gains a transmission advantage through a combination of paternal-effect killing and zygotic self-rescue. Here we demonstrate that this element is composed of a sperm-delivered toxin, peel-1, and an embryo-expressed antidote, zeel-1. peel-1 and zeel-1 are located adjacent to one another in the genome and co-occur in an insertion/deletion polymorphism. peel-1 encodes a novel four-pass transmembrane protein that is expressed in sperm and delivered to the embryo via specialized, sperm-specific vesicles. In the absence of zeel-1, sperm-delivered PEEL-1 causes lethal defects in muscle and epidermal tissue at the 2-fold stage of embryogenesis. zeel-1 is expressed transiently in the embryo and encodes a novel six-pass transmembrane domain fused to a domain with sequence similarity to zyg-11, a substrate-recognition subunit of an E3 ubiquitin ligase. zeel-1 appears to have arisen recently, during an expansion of the zyg-11 family, and the transmembrane domain of zeel-1 is required and partially sufficient for antidote activity. Although PEEL-1 and ZEEL-1 normally function in embryos, these proteins can act at other stages as well. When expressed ectopically in adults, PEEL-1 kills a variety of cell types, and ectopic expression of ZEEL-1 rescues these effects. Our results demonstrate that the tight physical linkage between two novel transmembrane proteins has facilitated their co-evolution into an element capable of promoting its own transmission to the detriment of organisms carrying it.
Semele: A Killer-male, rescue-female system for suppression and replacement of insect disease vector populations
4207Marshall, JMP, G. W.; Buchman, A. B.; Hay, B. A., Genetics, 187:535-551. 2011-01-05 00:00:00.
Two strategies to control mosquito-borne diseases, such as malaria and dengue fever, are reducing mosquito population sizes or replacing populations with disease-refractory varieties. We propose a genetic system, Semele, which may be used for both. Semele consists of two components: a toxin expressed in transgenic males that either kills or renders infertile wild-type female recipients and an antidote expressed in females that protects them from the effects of the toxin. An all-male release results in population suppression because wild-type females that mate with transgenic males produce no offspring. A release that includes transgenic females results in gene drive since females carrying the allele are favored at high population frequencies. We use simple population genetic models to explore the utility of the Semele system. We find that Semele can spread under a wide range of conditions, all of which require a high introduction frequency. This feature is desirable since transgenic insects released accidentally are unlikely to persist, transgenic insects released intentionally can be spatially confined, and the element can be removed from a population through sustained release of wild-type insects. We examine potential barriers to Semele gene drive and suggest molecular tools that could be used to build the Semele system.
Inverse Medea as a novel gene drive system for socal population replacement: A theoretical analysis
4206Marshall, JMH, B. A., Journal of Heredity, 102:336-341. 2011-01-04 00:00:00.
One strategy to control mosquito-borne diseases, such as malaria and dengue fever, on a regional scale is to use gene drive systems to spread disease-refractory genes into wild mosquito populations. The development of a synthetic Medea element that has been shown to drive population replacement in laboratory Drosophila populations has provided encouragement for this strategy but has also been greeted with caution over the concern that transgenes may spread into countries without their consent. Here, we propose a novel gene drive system, inverse Medea, which is strong enough to bring about local population replacement but is unable to establish itself beyond an isolated release site. The system consists of 2 genetic components-a zygotic toxin and maternal antidote-which render heterozygous offspring of wild-type mothers unviable. Through population genetic analysis, we show that inverse Medea will only spread when it represents a majority of the alleles in a population. The element is best located on an autosome and will spread to fixation provided any associated fitness costs are dominant and to very high frequency otherwise. We suggest molecular tools that could be used to build the inverse Medea system and discuss its utility for a confined release of transgenic mosquitoes.
Gene-drive into insect populations with age and spatial structure: a theoretical assessment
4205Huang, YXL, A. L.; Legros, M.; Gould, F., Evolutionary Applications, 4:415-428. 2011-01-03 00:00:00.
The potential benefits and risks of genetically engineered gene-drive systems for replacing wild pest strains with more benign strains must be assessed prior to any field releases. We develop a computer simulation model to assess the feasibility of using engineered underdominance constructs to drive transgenes into age- and spatially structured mosquito populations. Our practical criterion for success is the achievement of a transgene frequency of at least 0.80 within 3 years of release. The impacts of a number of parameters that may affect the success of gene-drive, such as the release area, release age, density-dependent larval survival, fitness cost of the engineered genes, and migration probability of adults, are examined. Results show that patchy release generally requires the release of fewer engineered insects to achieve success than central release. When the fitness cost is very low, central release covering 25% of the total area can be more effective than a completely uniform release over the whole area. This study demonstrates that to determine the best method of spatial release, and the total number of engineered insects that must be released, it is important to take into account the age and sex of the released insects and spatial structure of the population.
Selective microspore abortion correlated with aneuploidy: an indication of meiotic drive
4204Furness, CAR, P. J., Sexual Plant Reproduction, 24:1-8. 2011-01-02 00:00:00.
Selective megaspore abortion (monomegaspory) probably arose once in seed plants and occurs routinely in more than 70% of angiosperm species, representing one of the key characters of a heterosporous life history. In contrast, selective microspore abortion leading to pollen dispersal as pseudomonads (here termed monomicrospory) apparently arose at least twice independently within angiosperms, though it occurs in a limited number of taxa. Remarkably, similar examples of monomicrospory occur in members of two distantly related angiosperm families: the sedge family (Cyperaceae) and the epacrid subfamily (Styphelioideae) of the eudicot family Ericaceae. In sedges, monomicrospory is derived directly from normal tetrads, whereas epacrid pseudomonads apparently evolved via an intermediate stage, in which variable sterility occurs in a single tetrad. Our comparison of these two examples of selective microspore abortion highlights a correlation with aneuploidy, indicating that non-random chromosome segregation caused by monomicrospory could drive chromosomal mutations to rapid fixation through meiotic drive.
Polar bodies–more a lack of understanding than a lack of respect
8196S. Schmerler and G. M. Wessel, Molecular Reproduction and Development, 78:3-8. 2010-12-30 20:20:23.
Polar bodies are as diverse as the organisms that produce them. Although in many animals these cells often die following meiotic maturation of the oocyte, in other organisms they are an essential and diverse part of embryonic development. Here we highlight some of this diversity and summarize the evolutionary basis for their
On the Well Posedness and Refined Estimates for the Global Attractor of the TYC Model
11541R. D. Parshad and J. B. Gutierrez, Boundary Value Problems, 2010-11-22 17:23:35.
The Trojan Y Chromosome strategy (TYC) is a theoretical method for eradication of invasive species. It requires constant introduction of artificial individuals into a target population, causing a shift in the sex ratio that ultimately leads to local extinction. In this work we demonstrate the existence of a unique weak solution to the infinite dimensional TYC system. Furthermore, we obtain improved estimates on the upper bounds for the Hausdorff and fractal dimensions of the global attractor of the TYC system, via the use of weighted Sobolev spaces. These results confirm that the TYC eradication strategy is a sound theoretical method of eradication of invasive species in a spatial setting. It also provides a solid ground for experiments in silico and validates the use of the TYC strategy in vivo.
Problem formulation in the environmental risk assessment for genetically modified plants
4219Wolt, JDK, Paul; Raybould, Alan; Fitzpatrick, Julie W.; Burachik, Moisés; Gray, Alan; Olin, Stephen S.; Schiemann, Joachim; Sears, Mark; Wu, Felicia, Transgenic Research, 19:425-436. 2010-01-17 00:00:00.
Problem formulation is the first step in environmental risk assessment (ERA) where policy goals, scope, assessment endpoints, and methodology are distilled to an explicitly stated problem and approach for analysis. The consistency and utility of ERAs for genetically modified (GM) plants can be improved through rigorous problem formulation (PF), producing an analysis plan that describes relevant exposure scenarios and the potential consequences of these scenarios. A properly executed PF assures the relevance of ERA outcomes for decision-making. Adopting a harmonized approach to problem formulation should bring about greater uniformity in the ERA process for GM plants among regulatory regimes globally. This paper is the product of an international expert group convened by the International Life Sciences Institute (ILSI) Research Foundation.
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.
The role of meiotic drive in hybrid male sterility
4217McDermott, SRN, M. A. F., Philosophical Transactions of the Royal Society B-Biological Sciences, 365:1265-1272. 2010-01-15 00:00:00.
Meiotic drive causes the distortion of allelic segregation away from Mendelian expected ratios, often also reducing fecundity and favouring the evolution of drive suppressors. If different species evolve distinct drive-suppressor systems, then hybrid progeny may be sterile as a result of negative interactions of these systems' components. Although the hypothesis that meiotic drive may contribute to hybrid sterility, and thus species formation, fell out of favour early in the 1990s, recent results showing an association between drive and sterility have resurrected this previously controversial idea. Here, we review the different forms of meiotic drive and their possible roles in speciation. We discuss the recent empirical evidence for a link between drive and hybrid male sterility, also suggesting a possible mechanistic explanation for this link in the context of chromatin remodelling. Finally, we revisit the population genetics of drive that allow it to contribute to speciation.
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
Games in tetrads: Segregation, recombination, and meiotic drive
4215Haig, D, American Naturalist, 176:404-413. 2010-01-13 00:00:00.
The two alleles at a heterozygous locus segregate during meiosis, sometimes at meiosis I and sometimes at meiosis II. The timing of segregation is determined by the pattern of crossing-over between a locus and its attached centromeres. Genes near centromeres can exploit this process by driving against spores from which the genes separated at meiosis I. Other genes, located distal to centromeres, can benefit from driving against spores from which they separated at meiosis II. Asymmetric female meiosis is particularly susceptible to such forms of drive. Selection on modifiers of recombination favors changes in the location of chiasmata that increase the proportion of tetrads of high average fitness by changing the timing of segregation. Such changes increase the frequency of driving alleles. This source of selection on recombination does not depend on effects on linkage disequilibrium. Recombinational responses to meiotic drive may contribute to sex differences in overall recombination and sex differences in the localization of chiasmata.
Segregation analysis of a sex ratio distortion locus in congenic mice
4214Casellas, JF, C. R.; Verdugo, R. A.; Medrano, J. F., Journal of Heredity, 101:351-359. 2010-01-12 00:00:00.
The congenic HG.CAST-(D17Mit196-D17Mit190) (HQ17(hg/hg)) mouse strain showed a significant departure on the expected 50%/50% offspring sex ratio in more than 2400 progeny (55.7% females). The entire pedigree file included data from 13 nonoverlapping purebred generations and an F-2 cross with the C57BL/6J inbred strain. Offspring sex ratio data were analyzed on the basis of 40 purebred HQ17(hg/hg) sires and 29 F-1 HQ17(hg/hg) x B6 sires under a Bayesian Binomial segregation model accounting for 4 different autosomal inheritance models of gene action (i.e., additive, dominance, recessive, and overdominance) and X-linked and Y-linked loci. For each model, the segregation effect was evaluated as a single regression coefficient for all sires or assuming 2 independent regression coefficients accounting for offspring sex ratio departures in purebred and F-1 sires, respectively. The deviance information criterion clearly favored the autosomal dominance model with different regression coefficients for the 2 groups of sires. Under this model, the dominance effect increased the percentage of female offspring by 4.3% (HQ17(hg/hg) purebred sires) and 8.2% (F-1 sires) with the highest posterior density regions ranging from 0.5% to 10.6% and from 1.3% to 14.4%, respectively. This article provides significant evidence of genetic determinism for sex ratio distortion in the HQ17(hg/hg) strain and develops new analytical tools to perform segregation studies on dichotomous traits.
Segregation distortion in chicken and the evolutionary consequences of female meiotic drive in birds
4213Axelsson, EA, A.; Van, A. P.; Li, L.; Megens, H. J.; Vereijken, A. L. J.; Crooijmans, Rpma; Groenen, M. A. M.; Ellegren, H.; Willerslev, E.; Nielsen, R., Heredity, 105:290-298. 2010-01-11 00:00:00.
As all four meiotic products give rise to sperm in males, female meiosis result in a single egg in most eukaryotes. Any genetic element with the potential to influence chromosome segregation, so that it is preferentially included in the egg, should therefore gain a transmission advantage; a process termed female meiotic drive. We are aware of two chromosomal components, centromeres and telomeres, which share the potential to influence chromosome movement during meioses and make the following predictions based on the presence of female meiotic drive: (1) centromere-binding proteins should experience rapid evolution as a result of a conflict between driving centromeres and the rest of the genome; and (2) segregation patterns should be skewed near centromeres and telomeres. To test these predictions, we first analyze the molecular evolution of seven centromere-binding proteins in nine divergent bird species. We find strong evidence for positive selection in two genes, lending support to the genomic conflict hypothesis. Then, to directly test for the presence of segregation distortion, we also investigate the transmission of B9000 single-nucleotide polymorphisms in 197 chicken families. By simulating fair Mendelian meioses, we locate chromosomal regions with statistically significant transmission ratio distortion. One region is located near the centromere on chromosome 1 and a second region is located near the telomere on the p-arm of chromosome 1. Although these observations do not provide conclusive evidence in favour of the meiotic drive/genome conflict hypothesis, they do lend support to the hypothesis that centromeres and telomeres drive during female meioses in chicken. Heredity (2010) 105, 290-298; doi:10.1038/hdy.2009.193; published online 27 January 2010
Using underdominance to bi-stably transform local populations
4212Altrock, PMT, A.; Reeves, R. G.; Reed, F. A., Journal of Theoretical Biology, 267:62-75. 2010-01-10 00:00:00.
Underdominance refers to natural selection against individuals with a heterozygous genotype. Here, we analyze a single-locus underdominant system of two large local populations that exchange individuals at a certain migration rate. The system can be characterized by fixed points in the joint allele frequency space. We address the conditions under which underdominance can be applied to transform a local population that is receiving wildtype immigrants from another population. In a single population, underdominance has the benefit of complete removal of genetically modified alleles (reversibility) and coexistence is not stable. The two population system that exchanges migrants can result in internal stable states, where coexistence is maintained, but with additional release of wildtype individuals the system can be reversed to a fully wildtype state. This property is critically controlled by the migration rate. We approximate the critical minimum frequency required to result in a stable population transformation. We also concentrate on the destabilizing effects of fitness and migration rate asymmetry. Practical implications of our results are discussed in the context of utilizing underdominance to genetically modify wild populations. This is of importance especially for genetic pest management strategies, where locally stable and potentially reversible transformations of populations of disease vector species are of interest. (C) 2010 Elsevier Ltd. All rights reserved.
On the global attractor of the Trojan Y chromosome model.
11536R. D. Parshad and J. B. Gutierrez, Communications on Pure and Applied Analysis, 10:339-359. 2010-01-01 17:11:02.
We consider the Trojan Y Chromosome (TYC) model for eradication of invasive species in population dynamics. We present global estimates for the TYC system in a spatial domain. In this work we prove the existence of a global attractor for the system. We derive uniform estimates to tackle the question of asymptotic compactness of the semi-group for the TYC model in H(2)(Omega). This along with the existence of a bounded absorbing set, which we also derive, demonstrates the existence of a global attractor for the TYC model. The present analysis reveals that extinction of an invasive species is always possible to achieve irrespective of geometric considerations of the domain. This result is valid for TYC systems in which advection is negligible. This theoretical work lays the foundation for experimental studies of the application of the TYC eradication strategy in spatial ecology, since the outcome is in principle guaranteed.
Ethical, legal and social aspects of the approach in Sudan
25823B. B. El Sayed, C. A. Malcolm, A. Babiker, E. M. Malik, M. A. H. El Tayeb, N. S. Saeed, A. H. D. Nugud and B. G. J. Knols, Malaria Journal, 8:S3. 2009-11-16 10:10:31.
The global malaria situation, especially in Africa, and the problems frequently encountered in chemical control of vectors such as insecticide resistance, emphasize the urgency of research, development and implementation of new vector control technologies that are applicable at regional and local levels. The successful application of the sterile insect technique (SIT) for the control of the New World screwworm Cochliomyia hominivorax and several species of fruit flies has given impetus to the use of this method for suppression or elimination of malaria vectors in some areas of Africa including Northern State of Sudan. The research and development phase of the Northern State feasibility study has been started. Sudanese stakeholders are working side-by-side with the International Atomic Energy Agency in the activities of this important phase. Several ethical, legal and social issues associated with this approach arose during this phase of the project. They need to be seriously considered and handled with care. In this paper, these issues are described, and the current and proposed activities to overcome potential hurdles to ensure success of the project are listed.
Field site selection: getting it right first time around
25817C. A. Malcolm, B. El Sayed, A. Babiker, R. Girod, D. Fontenille, B. G. J. Knols, A. H. Nugud and M. Q. Benedict, Malaria Journal, 8. 2009-11-16 09:57:52.
The selection of suitable field sites for integrated control of Anopheles mosquitoes using the sterile insect technique (SIT) requires consideration of the full gamut of factors facing most proposed control strategies, but four criteria identify an ideal site: 1) a single malaria vector, 2) an unstructured, relatively low density target population, 3) isolation of the target population and 4) actual or potential malaria incidence. Such a site can exist in a diverse range of situations or can be created. Two contrasting SIT field sites are examined here: the desert-flanked Dongola Reach of the Nile River in Northern State, Sudan, where malaria is endemic, and the island of La Reunion, where autochthonous malaria is rare but risk is persistent. The single malaria-transmitting vector at both sites is Anopheles arabiensis. In Sudan, the target area is a narrow 500 km corridor stretching from the rocky terrain at the Fourth Cataract - just above the new Merowe Dam, to the northernmost edge of the species range, close to Egypt. Vector distribution and temporal changes in density depend on the Nile level, ambient temperature and human activities. On La Reunion, the An. arabiensis population is coastal, limited and divided into three areas by altitude and exposure to the trade winds on the east coast. Mosquito vectors for other diseases are an issue at both sites, but of primary importance on La Reunion due to the recent chikungunya epidemic. The similarities and differences between these two sites in terms of suitability are discussed in the context of area-wide integrated vector management incorporating the SIT.
Genetic control of invasive plants species using selfish genetic elements
13612K. A. Hodgins, L. Rieseberg and S. P. Otto, Evolutionary Applications, 2:555-569. 2009-10-30 13:00:19.
Invasive plants cause substantial environmental damage and economic loss. Here, we explore the possibility that a selfish genetic element found in plants called cytoplasmic male sterility (CMS) could be exploited for weed control. We developed an analytical model and a spatial simulation to assess the use of CMS alleles to manage weed populations.
Spatial and temporal distribution of the malaria mosquito Anopheles arabiensis in northern Sudan: influence of environmental factors and implications for vector control
25826T. B. Ageep, J. Cox, M. M. Hassan, B. G. J. Knols, M. Q. Benedict, C. A. Malcolm, A. Babiker and B. B. El Sayed, Malaria Journal, 8:14. 2009-06-09 10:20:40.
Background: Malaria is an important public health problem in northern Sudan, but little is known about the dynamics of its transmission. Given the characteristic low densities of Anopheles arabiensis and the difficult terrain in this area, future vector control strategies are likely to be based on area-wide integrated pest management (AW-IPM) that may include the sterile insect technique ( SIT). To support the planning and implementation of future AW-IPM activities, larval surveys were carried out to provide key data on spatial and seasonal dynamics of local vector populations. Methods: Monthly cross-sectional larval surveys were carried out between March 2005 and May 2007 in two localities (Dongola and Merowe) adjacent to the river Nile. A stratified random sampling strategy based on the use of Remote Sensing (RS), Geographical Information Systems (GIS) and the Global Positioning System (GPS) was used to select survey locations. Breeding sites were mapped using GPS and data on larval density and breeding site characteristics were recorded using handheld computers. Bivariate and multivariate logistic regression models were used to identify breeding site characteristics associated with increased risk of presence of larvae. Seasonal patterns in the proportion of breeding sites positive for larvae were compared visually to contemporaneous data on climate and river height. Results: Of a total of 3,349 aquatic habitats sampled, 321 (9.6%) contained An. arabiensis larvae. The frequency with which larvae were found varied markedly by habitat type. Although most positive sites were associated with temporary standing water around the margins of the main Nile channel, larvae were also found at brickworks and in areas of leaking pipes and canals-often far from the river. Close to the Nile channel, a distinct seasonal pattern in larval populations was evident and appeared to be linked to the rise and fall of the river level. These patterns were not evident in vector populations breeding in artificial water sources away from the river. Conclusion: The GIS-based survey strategy developed in this study provides key data on the population dynamics of An. arabiensis in Northern State. Quantitative estimates of the contributions of various habitat types and their proximity to settlements provide a basis for planning a strategy for reducing malaria risk by elimination of the vector population.
Testosterone has a long-term effect on primary sex ratio of first eggs in pigeons-in search of a mechanism
4223Goerlich, VCD, C.; Schaafsma, S. M.; Groothuis, T. G. G., General and Comparative Endocrinology, 163:184-192. 2009-01-21 00:00:00.
Despite accumulating evidence that birds, in which females are the heterogametic sex, are able to manipulate primary offspring sex ratio, the underlying mechanism remains elusive. Steroid hormones. which govern female reproduction and are also accumulated by the developing follicle could potentially affect primary sex ratio by differential follicle development in relation to future sex and meiotic drive, or by sex specific influence on oocyte abortion or fertilization. So far, experimental results on the involvement of maternal testosterone (T) in offspring sex manipulation are ambiguous. To investigate the effect of T on primary sex ratio and elucidate underlying mechanisms, we elevated circulating T levels in female homing pigeons (Columba livia). During the course of the experiment females produced three clutches-before and during T implantation, and one year after implant removal. Intriguingly, first eggs, but not second eggs of T females were significantly male biased relative to sham-implanted controls. One year after cessation of the treatment the male bias was still present, indicating long-term effects on female reproductive physiology. T treatment did not affect maternal body condition, nor was body condition correlated with offspring sex ratio. Our data on timing of oviposition, lack of infertile eggs, and yolk weight indicate a possible role for sex specific follicle abortion, perhaps in combination with meiotic drive. However, despite T treatment elevating maternal plasma levels, egg yolk T concentrations did not differ between treatment groups and did not vary with embryo sex, suggesting that yolk T is not involved in meiotic drive. (C) 2009 Elsevier Inc. All rights reserved.
Molecular signature of epistatic selection: interrogating genetic interactions in the sex-ratio meiotic drive of Drosophila simulans
4222Chevin, LMB, H.; Montchamp-Moreau, C.; Hospital, F., Genetics Research, 91:171-182. 2009-01-20 00:00:00.
Fine scale analyses Of signatures of selection allow assessing quantitative aspects of a Species' evolutionary genetic history, such as the strength of selection on genes. When several selected loci lie in the same genomic region, their epistatic interactions may also be investigated. Here. we Study how the neutral polymorphism pattern was shaped by two close recombining loci that cause 'sex-ratio' meiotic drive in Drosophila simulans, as an example of strong selection with potentially strong epistasis. We compare the polymorphism data observed in a natural population with the results of forward stochastic simulations under several contexts of epistasis between the candidate loci for the drive. We compute the likelihood of different possible scenarios. in order to determine which configuration is most consistent with the data. Our results highlight that fine scale analyses of well-chosen candidate genomic regions provide information-rich data that can be used to investigate the genotype-phenotype-fitness map. which can hardly be Studied in genome-wide analyses. We also emphasize that initial conditions and time of observation (here, time after the Interruption Of a partial selective sweep) are crucial parameters in the interpretation of real data, while these are often overlooked in theoretical studies.
Evolution of the Schlafen genes, a gene family associated with embryonic lethality, meiotic drive, immune processes and orthopoxvirus virulence
4221Bustos, ON, S.; Ayers, G.; Casola, C.; Perez-Lamigueiro, M. A.; Chippindale, P. T.; Pritham, E. J.; de la Casa-Esperon, E., Gene, 447:11-Jan. 2009-01-19 00:00:00.
Genes of the Schlafen family, first discovered in mouse, are expressed in hematopoietic cells and are involved in immune processes. Previous results showed that they are candidate genes for two major phenomena: meiotic drive and embryonic lethality (DDK syndrome). However, these genes remain poorly understood, mostly due to the limitations imposed by their similarity, close location and the potential functional redundancy of the gene family members. Here we use genomic and phylogenetic studies to investigate the evolution and role of this family of genes. Our results show that the Schlafen family is widely distributed in mammals, where we recognize four major clades that experienced lineage-specific expansions or contractions in various orders, including primates and rodents. In addition, we identified members of the Schlafen family in Chondrichthyes and Amphibia, indicating an ancient origin of these genes. We find evidence that positive selection has acted on many Schlafen genes. Moreover, our analyses indicate that a member of the Schlafen family was horizontally transferred from murine rodents to orthopoxviruses, where it is hypothesized to play a role in allowing the virus to survive host immune defense mechanisms. The functional relevance of the viral Schlafen sequences is further underscored by our finding that they are evolving under purifying selection. This is of particular importance, since orthopoxviruses infect mammals and include variola, the causative agent of smallpox, and monkeypox, an emerging virus of great concern for human health. (C) 2009 Elsevier B.V. All rights reserved.
Deployment of innovative genetic vector control strategies: progress on regulatory and biosafety aspects, capacity building and development of best-practice guidance
4220Beech, CV, S.S.; Quinlan, M.M.; Capurro, Margareth L.; Alphey, L.; Bayard, V.; Bouare, M.; McLeod, M.C.; Kittayapong, P.; Lavery, J.; Lim, L.H.; Marrelli, M.T.; Nagaraju, J.; Ombongi, K.; Othman, R.Y.; Pillai, V.; Ramsey, J.; Reuben, R.; Rose, R.I.; Tyagi, B.K.; Mumford, J., AsPac J. Mol. Biol. Biotechnol., 17:75-85. 2009-01-18 00:00:00.
In the ongoing fight against vectors of human diseases, disease endemic countries (DECs) may soon benefit from innovative control strategies involving modified insect vectors. For instance, three promising methods (viz. RIDL® [Release of Insects with a Dominant Lethal], Wolbachia infection, and refractory mosquito technology) are being developed by researchers around the world to combat Aedes aegypti, the primary mosquito vector of viral fevers such as dengue (serotypes 1–4), chikungunya and yellow fever. Some of these techniques are already being extended to other vectors such as Aedes albopictus (the secondary vector of these diseases) and Anopheles mosquito species that transmit malaria. To enable DECs to take advantage of these promising methods, initiatives are underway that relate to biosafety, risk assessment and management, and ethical–social–cultural (ESC) aspects to consider prior to and during the possible deployment of these technologies as part of an integrated vector control programme. This is a brief overview of the objectives and timelines of some of the initiatives being championed by international institutions, including the United Nations Development Programme (UNDP), the World Health Organization (WHO) and the Grand Challenges in Global Health (GCGH) initiative co-sponsored by the Bill & Melinda Gates Foundation.
Assessment of transmission distortion on chromosome 6p in healthy individuals using tagSNPs
4231Santos, PSCH, J.; Schlattmann, P.; Konig, I. R.; Ziegler, A.; Uchanska-Ziegler, B., European Journal of Human Genetics, 17:1182-1189. 2009-01-09 00:00:00.
The best-documented example for transmission distortion (TD) to normal offspring are the t haplotypes on mouse chromosome 17. In healthy humans, TD has been described for whole chromosomes and for particular loci, but multiple comparisons have presented a statistical obstacle in wide-ranging analyses. Here we provide six high-resolution TD maps of the short arm of human chromosome 6 (Hsa6p), based on single-nucleotide polymorphism (SNP) data from 60 trio families belonging to two ethnicities that are available through the International HapMap Project. We tested all approximately 70 000 previously genotyped SNPs within Hsa6p by the transmission disequilibrium test. TagSNP selection followed by permutation testing was performed to adjust for multiple testing. A statistically significant evidence for TD was observed among male parents of European ancestry, due to strong and wide-ranging skewed segregation in a 730 kb long region containing the transcription factor-encoding genes SUPT3H and RUNX2, as well as the microRNA locus MIRN586. We also observed that this chromosomal segment coincides with pronounced linkage disequilibrium (LD), suggesting a relationship between TD and LD. The fact that TD may be taking place in samples not selected for a genetic disease implies that linkage studies must be assessed with particular caution in chromosomal segments with evidence of TD. European Journal of Human Genetics (2009) 17, 1182-1189; doi:10.1038/ejhg.2009.16; published online 4 March 2009
Multi-Locus Assortment (MLA) for transgene dispersal and elimination in mosquito populations
4230Rasgon, JL, PLOS One, 4:e5833. 2009-01-08 00:00:00.
: Replacement of wild-type mosquito populations with genetically modified versions is being explored as a potential strategy to control vector-borne diseases. Due to lower expected relative fitness of transgenic individuals, transgenes must be driven into populations for these scenarios to be successful. Several gene drive mechanisms exist in a theoretical sense but none are currently workable in mosquitoes. Even if strategies were workable, it would be very difficult to recall released transgenes in the event of unforeseen consequences. What is needed is a way to test transgenes in the field for feasibility, efficacy and safety prior to releasing an active drive mechanism. Methodology/Principal Findings: We outline a method, termed Multi-locus assortment (MLA), to spread transgenes into vector populations by the release of genetically-modified mosquitoes carrying multiple stable transgene inserts. Simulations indicate that [1] insects do not have to carry transgenes at more than 4 loci, [2] transgenes can be maintained at high levels by sequential small releases, the frequency of which depends on the construct fitness cost, and [3] in the case of unforeseen negative non-target effects, transgenes can be eliminated from the population by halting transgenic releases and/or mass releases of wild-type insects. We also discuss potential methods to create MLA mosquito strains in the laboratory. Conclusions/Significance: While not as efficient as active drive mechanisms, MLA has other advantages: [1] MLA strains can be constructed for some mosquito species with currently-available technology, [2] MLA will allow the ecological components of transgenic mosquito releases to be tested before actual gene drive mechanisms are ready to be deployed, [3] since MLA is not self-propagating, the risk of an accidental premature release into nature is minimized, and [4] in the case that active gene drive mechanisms prove impossible to develop, the MLA approach can be used as a back-up transgene dispersal mechanism for disease control efforts in some systems.
Large-scale selective sweep among Segregation Distorter chromosomes in African populations Drosophila melanogaster
4229Presgraves, DCG, P. R.; Cherukuri, A.; Lyttle, T. W., PLOS Genetics, 5:e1000463. 2009-01-07 00:00:00.
Segregation Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 of Drosophila melanogaster that strongly distorts Mendelian transmission; heterozygous SD/SD(+) males sire almost exclusively SD-bearing progeny. Fifty years of genetic, molecular, and theory work have made SD one of the best-characterized meiotic drive systems, but surprisingly the details of its evolutionary origins and population dynamics remain unclear. Earlier analyses suggested that the SD system arose recently in the Mediterranean basin and then spread to a low, stable equilibrium frequency (1-5%) in most natural populations worldwide. In this report, we show, first, that SD chromosomes occur in populations in sub-Saharan Africa, the ancestral range of D. melanogaster, at a similarly low frequency (similar to 2%), providing evidence for the robustness of its equilibrium frequency but raising doubts about the Mediterranean-origins hypothesis. Second, our genetic analyses reveal two kinds of SD chromosomes in Africa: inversion-free SD chromosomes with little or no transmission advantage; and an African-endemic inversion-bearing SD chromosome, SD-Mal, with a perfect transmission advantage. Third, our population genetic analyses show that SD-Mal chromosomes swept across the African continent very recently, causing linkage disequilibrium and an absence of variability over 39% of the length of the second chromosome. Thus, despite a seemingly stable equilibrium frequency, SD chromosomes continue to evolve, to compete with one another, or evade suppressors in the genome.
Drive and sperm: The evolution and genetics of male meiotic drive
4228Presgraves, D, Sperm Biology: an Evolutionary Perspective, 12:471-506. 2009-01-06 00:00:00.
Some selfish genetic elements in eukaryotic genomes have been harnessed to perform essential functions for their hosts, whereas others have gained transmission advantages at the expense of their hosts. Meiotic drive elements are particularly dramatic examples of the latter. Meiotic drive is the unequal—and thus non-Mendelian—transmission of alternative alleles or chromosomes from heterozygotes. Most drive elements achieve greater than Mendelian transmission from their carriers by excluding, impairing or killing competing alternative gametes. The best-characterized drive elements are the Segregation Distorter (SD) complex in the fruitfly Drosophila melanogaster and the t-haplotype in the Mus house mouse species. Despite being found in very distantly related species, both meiotic drive systems share genetic and chromosomal features that appear to characterize meiotic drive systems in general. For these, and all systems characterized to date, drive involves an interaction between at least two loci in which a trans-acting drive allele at one locus impairs transmission of sensitive alleles at a cis-acting target locus. In effect, the drive allele produces a toxin that incapacitates sperm bearing sensitive forms of the target. Drive chromosomes bear a driver and a drive-insensitive target, whereas non-drive chromosomes lack the driver and typically carry a drivesensitive target. This chapter reviews the genetics, molecular basis, and evolutionary history of several well-characterized drive systems, and considers the impact of drive on spermatogenesis and sperm competition, including potential evolutionary responses of organisms to drive.
The effect of gene drive on containment of transgenic mosquitoes
4227Marshall, JM, Journal of Theoretical Biology, 258:250-265. 2009-01-05 00:00:00.
Mosquito-borne diseases such as malaria and dengue fever continue to be a major health problem through Much of the world. Several new potential approaches to disease control utilize gene drive to spread anti-pathogen genes into the mosquito Population. Prior to a release, these projects will require trials in outdoor cages from which transgenic mosquitoes may escape, albeit in small numbers. Most genes introduced in small numbers are very likely to be lost from the environment; however, gene drive mechanisms enhance the invasiveness of introduced genes. Consequently, introduced transgenes may be more likely to persist than ordinary genes following an accidental release. Here, we develop stochastic models to analyze the loss probabilities for several gene drive mechanisms, including homing endonuclease genes, transposable elements, Medea elements, the intracellular bacterium Wolbachia, engineered underdominance genes, and meiotic drive. We find that Medea and Wolbachia present the best compromise between invasiveness and containment for the six gene drive systems Currently being considered for the control of mosquito-borne disease. Published by Elsevier Ltd.
Major evolutionary transitions in centromere complexity
4226Malik, HSH, S., Cell, 138:1067-1082. 2009-01-04 00:00:00.
Centromeres are chromosomal elements that are both necessary and sufficient for chromosome segregation. However, the puzzlingly broad range in centromere complexity, from simple "point" centromeres to multi-megabase arrays of DNA satellites, has defied explanation. We posit that ancestral centromeres were epigenetically defined and that point centromeres, such as those of budding yeast, have derived from the partitioning elements of selfish plasmids. We further propose that the larger centromere sizes in plants and animals and the rapid evolution of their centromeric proteins is the result of an intense battle for evolutionary dominance due to the asymmetric retention of only one product of female meiosis.
Skeeter Buster: A stochastic, spatially explicit modeling tool for studying Aedes aegypti population replacement and population suppression strategies
4225Magori, KL, M.; Puente, M. E.; Focks, D. A.; Scott, T. W.; Lloyd, A. L.; Gould, F., PLOS Neglected Tropical Diseases, 3:e508. 2009-01-03 00:00:00.
Dengue is the most important mosquito-borne viral disease affecting humans. The only prevention measure currently available is the control of its vectors, primarily Aedes aegypti. Recent advances in genetic engineering have opened the possibility for a new range of control strategies based on genetically modified mosquitoes. Assessing the potential efficacy of genetic (and conventional) strategies requires the availability of modeling tools that accurately describe the dynamics and genetics of Ae. aegypti populations. Methodology/Principal findingsWe describe in this paper a new modeling tool of Ae. aegypti population dynamics and genetics named Skeeter Buster. This model operates at the scale of individual water-filled containers for immature stages and individual properties (houses) for adults. The biology of cohorts of mosquitoes is modeled based on the algorithms used in the non-spatial Container Inhabiting Mosquitoes Simulation Model (CIMSiM). Additional features incorporated into Skeeter Buster include stochasticity, spatial structure and detailed population genetics. We observe that the stochastic modeling of individual containers in Skeeter Buster is associated with a strongly reduced temporal variation in stage-specific population densities. We show that heterogeneity in container composition of individual properties has a major impact on spatial heterogeneity in population density between properties. We detail how adult dispersal reduces this spatial heterogeneity. Finally, we present the predicted genetic structure of the population by calculating F(ST) values and isolation by distance patterns, and examine the effects of adult dispersal and container movement between properties. Conclusions/SignificanceWe demonstrate that the incorporated stochasticity and level of spatial detail have major impacts on the simulated population dynamics, which could potentially impact predictions in terms of control measures. The capacity to describe population genetics confers the ability to model the outcome of genetic control methods. Skeeter Buster is therefore an important tool to model Ae. aegypti populations and the outcome of vector control measures.
Gene-drive in age-structured insect populations
4224Huang, YXL, A. L.; Legros, M.; Gould, F., Evolutionary Applications, 2:143-159. 2009-01-02 00:00:00.
To date, models of gene-drive mechanisms proposed for replacing wild-type mosquitoes with transgenic strains that cannot transmit diseases have assumed no age or mating structure. We developed a more detailed model to analyze the effects of age and mating-related factors on the number of engineered insects that must be introduced into a wild population to achieve successful gene-drive based on the Medea and engineered underdominance mechanisms. We found that models without age-structure and mating details can substantially overestimate or underestimate the numbers of engineered insects that must be introduced. In general, introduction thresholds are lowest when young adults are introduced. When both males and females are introduced, assortative mating by age has little impact on the introduction threshold unless the introduced females have diminished reproductive ability because of their age. However, when only males are introduced, assortative mating by age is generally predicted to increase introduction thresholds. In most cases, introduction thresholds are much higher for male-only introductions than for both-sex introductions, but when mating is nearly random and the introduced insects are adults with Medea constructs, male-only introductions can have somewhat lower thresholds than both-sex introductions. Results from this model suggest specific parameters that should be measured in field experiments.
Genes in conflict: The biology of selfish genetic elements
Burt, A. and R. Trivers, Genes in conflict: the biology of selfish genetic elements, 2008-12-30 20:03:34.In evolution, most genes survive and spread within populations because they increase the ability of their hosts (or their close relatives) to survive and reproduce. But some genes spread in spite of being harmful to the host organism—by distorting their own transmission to the next generation, or by changing how the host behaves toward relatives. As a consequence, different genes in a single organism can have diametrically opposed interests and adaptations. Covering all species from yeast to humans, Genes in Conflict is the first book to tell the story of selfish genetic elements, those continually appearing stretches of DNA that act narrowly to advance their own replication at the expense of the larger organism. As Austin Burt and Robert Trivers show, these selfish genes are a universal feature of life with pervasive effects, including numerous counter-adaptations. Their spread has created a whole world of socio-genetic interactions within individuals, usually completely hidden from sight. Genes in Conflict introduces the subject of selfish genetic elements in all its aspects, from molecular and genetic to behavioral and evolutionary. Burt and Trivers give us access for the first time to a crucial area of research—now developing at an explosive rate—that is cohering as a unitary whole, with its own logic and interconnected questions, a subject certain to be of enduring importance to our understanding of genetics and evolution.
Towards a sterile insect technique field release of Anopheles arabiensis mosquitoes in Sudan: Irradiation, transportation, and field cage experimentation
25755M. E. H. Helinski, M. M. Hassan, W. M. El-Motasim, C. A. Malcolm, B. G. J. Knols and B. El-Sayed, Malaria Journal, 7:10. 2008-04-25 10:09:22.
Background: The work described in this article forms part of a study to suppress a population of the malaria vector Anopheles arabiensis in Northern State, Sudan, with the Sterile Insect Technique. No data have previously been collected on the irradiation and transportation of anopheline mosquitoes in Africa, and the first series of attempts to do this in Sudan are reported here. In addition, experiments in a large field cage under near-natural conditions are described. Methods: Mosquitoes were irradiated in Khartoum and transported as adults by air to the field site earmarked for future releases (400 km from the laboratory). The field cage was prepared for experiments by creating resting sites with favourable conditions. The mating and survival of (irradiated) laboratory males and field-collected males was studied in the field cage, and two small-scale competition experiments were performed. Results: Minor problems were experienced with the irradiation of insects, mostly associated with the absence of a rearing facility in close proximity to the irradiation source. The small-scale transportation of adult mosquitoes to the release site resulted in minimal mortality (< 6%). Experiments in the field cage showed that mating occurred in high frequencies (i.e. an average of 60% insemination of females after one or two nights of mating), and laboratory reared males (i.e. sixty generations) were able to inseminate wild females at rates comparable to wild males. Based on wing length data, there was no size preference of males for mates. Survival of mosquitoes from the cage, based on recapture after mating, was satisfactory and approximately 60% of the insects were recaptured after one night. Only limited information on male competitiveness was obtained due to problems associated with individual egg laying of small numbers of wild females. Conclusion: It is concluded that although conditions are challenging, there are no major obstacles associated with the small-scale irradiation and transportation of insects in the current setting. The field cage is suitable for experiments and studies to test the competitiveness of irradiated males can be pursued. The scaling up of procedures to accommodate much larger numbers of insects needed for a release is the next challenge and recommendations to further implementation of this genetic control strategy are presented.
The Impact of Dissociation on Transposon-Mediated Disease Control Strategies
23831J. M. Marshall, Genetics, 178:1673-1682. 2008-03-01 23:54:22.
Vector-borne diseases such as malaria and dengue fever continue to be a major health concern through much of the world. The emergence of chloroquine-resistant strains of malaria and insecticide-resistant mosquitoes emphasize the need for novel methods of disease control. Recently, there has been much interest in the use of transposable elements to drive resistance genes into vector populations as a means of disease control. One concern that must be addressed before a release is performed is the potential loss of linkage between a transposable element and a resistance gene. Transposable elements such as P and hobo have been shown to produce internal deletion derivatives at a significant rate, and there is concern that a similar process could lead to loss of the resistance gene from the drive system following a transgenic release. Additionally, transposable elements such as Himar1 have been shown to transpose significantly more frequently when free of exogenous DNA. Here, we show that any transposon-mediated gene drive strategy must have an exceptionally low rate of dissociation if it is to be effective. Additionally, the resistance gene must confer a large selective advantage to the vector to surmount the effects of a moderate dissociation rate and transpositional handicap.
Sex ratio distorter reduces sperm competitive ability in an insect
4243Price, TARB, A. J.; Avent, T. D.; Snook, R. R.; Hurst, G. D. D.; Wedell, N., Evolution, 62:1644-1652. 2008-01-21 00:00:00.
Selfish genetic elements (SGEs) are ubiquitous in animals and often associated with low male fertility due to reduced sperm number in male carriers. In the fruit fly Drosophila pseudoobscura, the meiotic driving X chromosome "sex ratio" kills Y-bearing sperm in carrier males (SR males), resulting in female only broods. We competed SR males against the ejaculates of noncarrying standard males (ST males), and quantified the number of sperm transferred by SR and ST males to females. We show that SR males are very poor sperm competitors, which is partly related to transfer of fewer sperm during mating. However, sperm numbers alone cannot explain the observed paternity reduction, indicating SR males' sperm may be of reduced quality, possibly due to damage during the killing of the noncarrying Y-sperm. The reduction in sperm competitive ability due to SR is large enough to potentially stabilize the spread of sex ratio drive through populations. The poor sperm competitive ability of SR males coupled with their low fitness as mates could favor increased remating by females to reduce paternity by SR males. Given the generally poor performance of SGE-carrying males in sperm competition, this may generate strong selective pressure favoring polyandry in many species.
