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>

Stability properties of underdominance in finite subdivided populations

4198
Altrock, 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

4211
Windbichler, 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

4210
Werren, 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

4209
Shin, 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

4208
Seidel, 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

4207
Marshall, 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

4206
Marshall, 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

4205
Huang, 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

4204
Furness, 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

8196
S. 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

11541
R. 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

4219
Wolt, 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)

4218
Rendon, 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

4217
McDermott, 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

4216
Kozielska, 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

4215
Haig, 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

4214
Casellas, 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

4213
Axelsson, 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

4212
Altrock, 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.

11536
R. 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.

« First ‹ Previous 1 89 97 98 99 100 101 109 118 Next › Last »