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.
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A sex-ratio meiotic drive system in Drosophila simulans. II: An X-linked distorter

4255
Tao, YA, L.; Kingan, S. B.; Ke, Y.; Xiao, H.; Hartl, D. L.,  PLOS Biology,  5:2576-2588. 2007-01-13 00:00:00.
The evolution of heteromorphic sex chromosomes creates a genetic condition favoring the invasion of sex-ratio meiotic drive elements, resulting in the biased transmission of one sex chromosome over the other, in violation of Mendel's first law. The molecular mechanisms of sex-ratio meiotic drive may therefore help us to understand the evolutionary forces shaping the meiotic behavior of the sex chromosomes. Here we characterize a sex-ratio distorter on the X chromosome (Dox) in Drosophila simulans by genetic and molecular means. Intriguingly, Dox has very limited coding capacity. It evolved from another X-linked gene, which also evolved de nova. Through retrotransposition, Dox also gave rise to an autosomal suppressor, not much yang (Nmy). An RNA interference mechanism seems to be involved in the suppression of the Dox distorter by the Nmy suppressor. Double mutant males of the genotype dox; nmy are normal for both sex-ratio and spermatogenesis. We postulate that recurrent bouts of sex-ratio meiotic drive and its subsequent suppression might underlie several common features observed in the heterogametic sex, including meiotic sex chromosome inactivation and achiasmy.

Neurospora spore killers Sk-2 and Sk-3 suppress meiotic silencing by unpaired DNA

4254
Raju, NBM, R. L.; Shiu, P. T.,  Genetics,  176:43-52. 2007-01-12 00:00:00.
In Neurosphora, crassa., pairing of homologous DNA segments is monitored during meiotic prophase I. Any genes not paired with a homolog, as well as any paired homologs of that gene, are silenced during the sexual phase by a mechanism known as meiotic silencing by unpaired DNA (MSUD). Two genes required for MSUD have been described previously: Sad-1 (Suppressor of ascus dominance), encoding an RNA-directed RNA polymerase, and sad-2, encoding a protein that controls the perinuclear localization of SAD-1. Inactivation of either sad-1 or sad-2 suppresses MSUD. We have now shown that MSUD is also suppressed by either of two Spore killer strains, Sk-2 and Sk-3. These were both known to contain a haplotype segment that behaves as a meiotic drive element in heterozygous crosses of killer X sensitive. Progeny ascospores not carrying the killer element fail to mature and are inviable. Crosses homozygous for either of the killer haplotypes suppress MSUD even though ascospores are not killed. The killer activity maps to the same 30-unit-long region within which recombination is suppressed in killer X sensitive crosses. We suggest that the region contains a suppressor of MSUD.

Meiotic drive by the Y-linked D gene in Aedes aegypti (L.) (Diptera : Culicidae) is associated with disruption of spermiogenesis, leading to premature senescence of spermatozoa

4253
Owusu-Daaku, KOB, R. D.; Wood, R. J.,  Arthropod Structure & Development,  36:233-243. 2007-01-11 00:00:00.
Y chromosome meiotic drive in the mosquito Aedes aegypti, due to the gene D (Distorter) in coupling with M (male determination) [the MD haplotype], is associated with spermiogenic disruption, leading to senescence, at a rate Proportionate to male excess. Spermiogenesis was compared between 'Enhanced Mutant' males with a strongly female-depleted sex ratio (8.9% females), 'Mutant' males showing a lesser degree of distortion (38.3% females), and two controls with normal sex ratios (51.2% and 49.2% females). Sections of testes dissected front mature pupae and adults aged 0, 4, 8, 12 and 16 days were examined by transmission electron microscopy. A difference between Mutant and control spermiogenesis was apparent as early as the pupal stage when some Mutant spermatids showed extra tail elements (axonemes and/or mitochondrial derivatives). The same was true of Enhanced Mutant males but to a more extreme degree. Sperm senescence was evident in Enhanced Mutant testes from day 0 of adult life but in Mutant testes not until day 4. Progressive disorganisation was associated with many loose organelles, and disturbance of the anterior-posterior axis of gamete differentiation within the testis. Degenerative changes of a similar kind in the controls did not become apparent until day 8. These findings are discussed with respect to other characteristics of this meiotic drive system, in terms of a theory of inhibition of reduction division in spermatogenesis associated with fragmentation of the X chromosome, leading to the formation of a restitution nucleus as early as rnetaphase 1. (c) 2007 Elsevier Ltd. All rights reserved.

Identification and characterization of segregation distortion loci along chromosome 5B in tetraploid wheat

4252
Kumar, SG, B. S.; Faris, J. D.,  Molecular Genetics and Genomics,  278:187-196. 2007-01-10 00:00:00.
Segregation distortion genes are widespread in plants and animals and function by their effect on competition among gametes for preferential fertilization. In this study, we evaluated the segregation distortion of molecular markers in multiple reciprocal backcross populations derived from unique cytogenetic stocks involving the durum cultivar Langdon (LDN) and wild emmer accessions that allowed us to study the effects of chromosome 5B in isolation. No segregation distortion of female gametes was observed, but three populations developed to analyze segregation of male gametes had genomic regions containing markers with skewed segregation ratios. One region of distortion was due to preferential transmission of LDN alleles over wild emmer alleles through male gametes. Another region required the presence of LDN 5B chromosomes in the female for preferential fertilization by male gametes harboring LDN alleles indicating that the corresponding genes in the female gametes can govern genes affecting segregation distortion of male gametes. A third region of distortion was the result of preferential transmission of wild emmer alleles over LDN alleles through male gametes. These results indicate the existence of different distorter/meiotic drive elements among different genotypes and show that distortion factors along wheat chromosome 5B differ in chromosomal location as well as underlying mechanisms.

Introducing desirable transgenes into insect populations using Y-linked meiotic drive – A theoretical assessment

4251
Huang, YXM, K.; Lloyd, A. L.; Gould, F.,  Evolution,  61:717-726. 2007-01-09 00:00:00.
The use of genetic drive mechanisms to replace native mosquito genotypes with individuals bearing antipathogen transgenes is a potential strategy for repressing insect transmission of human diseases such as malaria and dengue. Antipathogen transgenes have been developed and tested, but efficient gene drive mechanisms are lacking. Here we theoretically assess the feasibility of introducing antipathogen genes into wild Aedes aegypti populations by using a naturally occurring meiotic drive system. We consider the release of males having both a Winked meiotic drive gene and an X-linked drive-insensitive response allele to which an antipathogen gene is linked. We use mathematical models and computer simulations to determine how the post-introduction dynamics of the antipathogen gene are affected by specific genetic characteristics of the system. The results show that when the natural population is uniformly sensitive to the meiotic drive gene, the antipathogen gene may be driven close to fixation if the fitness costs of the drive gene, the insensitive response allele, and the antipathogen gene are low. However, when the natural population has a small proportion of an X-linked insensitive response allele or an autosomal gene that strongly reduces the effect of the drive gene, the antipathogen gene does not spread if it has an associated fitness cost. Our modeling results provide a theoretical foundation for further experimental tests.

Introducing transgenes into insect populations using combined gene-drive strategies: Modeling and analysis

4250
Huang, YXM, K.; Lloyd, A. L.; Gould, F.,  Insect Biochemistry and Molecular Biology,  37:1054-1063. 2007-01-08 00:00:00.
Engineered underdominance (EU), meiotic drive (MD) and Wolbachia have been proposed as mechanisms for driving anti-pathogen transgenes into natural populations of insect vectors of human diseases. EU can drive transgenes to high and stable frequencies but requires the release of sizeable numbers of engineered insects. MD and Wolbachia either cannot maintain high frequencies of transgenes or lack appropriate expression in critical tissues, but both can drive the transgenes to spread from very low initial frequencies. Here we use mathematical models to assess the utility of combining EU with MD or with Wolbachia. Under some conditions, the combination of EU and MD results in a more efficient transgene-drive strategy than either mechanism alone. This combined strategy could drive the transgenes to stable fixation and would require fewer released insects than EU alone, especially when only males are released. However, a combination of EU and Wolbachia does not work better than EU alone because it requires the release of even more engineered insects. (C) 2007 Elsevier Ltd. All rights reserved.

Chromosome-wide linkage disequilibrium as a consequence of meiotic drive

4249
Dyer, KAC, B.; Jaenike, J.,  Proceedings of the National Academy of Sciences of the United States of America,  104:1587-1592. 2007-01-07 00:00:00.
Adaptation by natural selection proceeds most efficiently when alleles compete solely on the basis of their effects on the survival and reproduction of their carriers. A major condition for this is equal Mendelian segregation, but meiotic drive can short-circuit this process. The evolution of drive often involves multiple, interacting genetic components, together with enhancers and suppressors of drive. Chromosomal inversions that suppress crossing over are also frequently associated with drive systems. This study investigates the effects of these processes on patterns of molecular evolution in the fly Drosophila recens, which is polymorphic for a driving X chromosome (X-D). Whereas standard wild-type chromosomes exhibit high levels of polymorphism at multiple loci, all of the X-D chromosomes effectively carry a single multilocus haplotype that spans at least 130 cM. The X-D is associated with a complex set of inversions that completely suppresses recombination between the standard wild-type chromosome and X-D in heterozygous females, which maintain nonrandom associations among loci that presumably interact epistatically for the expression of drive. The long-term costs of foregoing recombination may be substantial; in combination with its low equilibrium frequency, this makes the XD chromosome susceptible to the accumulation of deleterious mutations. Consistent with this, X-D chromosomes are apparently fixed for a recessive mutation that causes female sterility. Thus, the X-D in D. recens appears to be in chromosome-wide linkage disequilibrium and in the early stages of mutational degradation.

A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila

4248
Chen, CHH, H. X.; Ward, C. M.; Su, J. T.; Schaeffer, L. V.; Guo, M.; Hay, B. A.,  Science,  316:597-600. 2007-01-06 00:00:00.
One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements in Drosophila that drive population replacement and are resistant to recombination-mediated dissociation of drive and disease refractoriness functions. These selfish elements use microRNA-mediated silencing of a maternally expressed gene essential for embryogenesis, which is coupled with early zygotic expression of a rescuing transgene.

First Anopheles arabiensis germline transformation: Toward the development of a transgenic genetic sexing strain

16649
H. C. Bossin, J. Thailayil, F. Catteruccia, J. P. Benton, A. Crisanti, M. Q. Benedict, B. G. Knols and A. S. Robinson,  American Journal of Tropical Medicine and Hygiene,  75:66-66. 2006-11-01 20:17:39.
The ability to genetically engineer mosquitoes is likely to have major implications for the development and implementation of genetic control systems against mosquito disease vectors such as the Sterile Insect Technique (SIT). In particular, genetically transformed mosquito strains can be created for genetic marking and sexing, two key factors known to influence the effectiveness of SIT programmes. In addition, the removal of biting females before releasing sterile males in the field will be of critical importance as they contribute to disease transmission and reduce the efficiency of the release campaign. Parallel to the creation of a conventional genetic sexing strain (Y-translocation of a resistance marker), our group is undertaking a transgenic approach to the development of an A. arabiensis genetic sexing strain (GSS). The sex separation strategy under investigation relies on the sex-specific properties of the A. gambiae B2tubulin gene regulatory regions. It is hoped this approach will achieve the high sex separation efficiency (above 99%) and strain stability required for safe and efficient male-only SIT releases. We report here the successful development of transgenic A. arabiensis lines using the pPB[DsRed]B2EGFP construct. Wild-type A. arabiensis embryos were injected with a mixture of pPB[DsRed]B2EGFP and helper plasmid phsp­pBac (700 and 300 ng/µI respectively) following an appropriate protocol.  Injections generated several transgenic sexing lines. The effectiveness of the transgenic-based sex-separation procedure, the stability of transgenic mosquito GSS under various (mass-)rearing regimes, as well as the viability and reproductive competitiveness of transgenic sterile males are being assessed.

The Sterile Insect Technique: can established technology beat malaria?

25843
M. E. H. Helinski, B. El-Sayed and B. G. J. Knols,  Entomologische Berichten,  66:13-20. 2006-06-06 14:48:37.
The Sterile Insect Technique (SIT) is the mass production, sterilisation and subsequent release of sterile insects into a target population in an area-wide integrated approach. The released sterile males mate with wild females; they thus no longer produce offspring and therefore the size of the target population is reduced. Over the years, SIT has proven to be a safe, effective and environmentally sound method to suppress, eliminate or contain pest populations. The International Atomic Energy Agency (IAEA) has a long history of supporting SIT programmes against key insect pests, including fruit flies, tsetse flies and moths. Recently, an integrated five year study to assess the feasibility of SIT to control African malaria mosquitoes has been initiated. In this article, we discuss the components and research requirements for such a feasibility study including sexing, mass production, sterilisation and release methodologies.

Radiation-induced sterility for pupal and adult stages of the malaria mosquito Anopheles arabiensis

25750
M. E. H. Helinski, A. G. Parker and B. G. J. Knols,  Malaria Journal,  5:10. 2006-05-16 15:23:31.
The optimal dose for male insects to be released in an SIT programme depends on their level of sterility and competitiveness. The use of semi-sterilizing doses to produce more competitive insects is discussed. The most convenient developmental stage for mosquito irradiation on a mass-scale are pupae, but pupal irradiation resulted in a lower insemination rate at the highest dose compared to adult irradiation. On the basis of this study, a suitable dose range that includes semi-sterilizing doses is identified to initiate competitiveness experiments for males irradiated at both developmental stages.

Genetic strategies for controlling mosquito-borne diseases

6191
F. Gould, K. Magori and Y. Huang,  American Scientist,  94:238. 2006-05-03 19:19:14.
Malaria kills more than a million people each year, primarily children under the age of six. Dengue fever is less deadly, but an outbreak can debilitate millions of people and easily overwhelm doctors and hospitals in tropical cities

The hitchhiking effect of an autosomal meiotic drive gene

4263
Chevin, LMH, F.,  Genetics,  173:1829-1832. 2006-01-21 00:00:00.
Transmission-ratio distortion is a departure from a 1:1 segregation of alleles in the gametes of a heterozygous individual. The so-called driving allele is strongly selected regardless of its effect on the fitness of the carrying individual. It may then have an important impact on neutral polymorphism due to the genetic hitchhiking effect. We study this hitchhiking effect in the case of true meiotic drive in autosomes and show that it is more dependent on the recombination rate than in the classical case of a gene positively selected at the organism level.

Cage trials using an endogenous meiotic drive gene in the mosquito Aedes aegypti to promote population replacement

4262
Cha, SJM, A.; Chadee, D. D.; Severson, D. W.,  American Journal of Tropical Medicine and Hygiene,  74:62-68. 2006-01-20 00:00:00.
Control of arthropod-borne diseases based on population replacement with genetically modified noncompetent vectors has been proposed as a promising alternative to conventional control strategies. Due to likely fitness costs associated with vectors manipulated to carry anti-pathogen effector genes, the effector genes will need to be coupled with a strong drive system to rapidly sweep them into natural populations. Endogenous meiotic drive systems have strong and stable population replacement potential, and have previously been reported in two mosquito species: Aedes aegypti and Culex pipiens. To investigate the influence of an endogenous meiotic drive gene on Ae. aegypti population dynamics, we established three experimental population types that were initiated with 100%, 10%, and 1% male mosquitoes carrying a strong meiotic driver (T37 strain) and 100% sensitive females (RED strain), respectively. Among the 100% and 10% populations, early generations were highly male biased, which reflected the effects of the meiotic driver, and remained more than 60% male by the F-15. A genetic marker tightly linked with the meiotic driver on chromosome 1 showed strong selection for the T37 strain-specific allele. Similar but reduced effects of the meiotic driver were also observed in the 1% populations. These results suggest that release of A e. aegypti males carrying a strong meiotic driver into drive sensitive populations can be an effective tool for population replacement, and provide a foundation for additional studies including both experimental populations and simulations by mathematical modeling.

Isolation and characterization of the RanGAP gene in the mosquito Aedes aegypti

4261
Cha, SJL, N.; Debruyn, B.; Severson, D. W.,  DNA Sequence,  17:223-230. 2006-01-19 00:00:00.
A duplicated 3'-truncated version of RanGAP was previously identified as Segregation distorter (Sd), the meiotic drive gene in Drosophila melanogaster. Here we report the cloning and characterization of the complete gene sequence for the RanGAP homolog from the mosquito Aedes aegypti. The 1995 bp cDNA sequence consists of a 113 bp 5'UTR and 130 bp 3'UTR, and encodes a 583 amino acid protein with high sequence identity with RanGAP homologues of several species. A 20,125 bp genomic DNA sequence contains the complete RanGAP gene, consisting of three exons and two introns. Intron 2 comprises 18,082 bp and contains multiple repetitive elements as well as putative coding regions. The RanGAP locus was mapped to the q-arm of chromosome 2. Because the meiotic drive gene (M-D) in A. aegpti was previously shown to be tightly linked with the sex determining locus on chromosome 1, RanGAP is likely not the M-D gene.

Population dynamics of an endogenous meiotic drive system in Aedes aegypti in Trinidad

4260
Cha, SJC, D. D.; Severson, D. W.,  American Journal of Tropical Medicine and Hygiene,  75:70-77. 2006-01-18 00:00:00.
An endogenous meiotic drive system was previously reported to be segregating in the yellow fever mosquito Aedes aegypti L. (Diptera: Culicidae) population in Trinidad. The meiotic driver (M-D) is tightly linked to the male determining locus and selectively targets sensitive responders linked to the female determining allele, causing fragmentation of female gametes. This results in highly male-biased progeny. The M-D system was initially studied as a genetic tool for population control with limited success, but recently interest has focused on its potential for population replacement. This study examines the distribution and dynamics of the M-D system in Trinidad natural populations. We obtained ovitrap samples from seven geographically distinct regions and determined the allele frequencies of the driver (M-D) and sensitive (m(s)) versus insensitive (m(i)) responders, respectively. Frequencies of the M-D allele ranged from 0.1 to 0.5 and were low at the two major port cities, Port of Spain and San Fernando, suggesting the effects of frequent immigration by non-driving genotypes. Frequencies of the m(i) allele ranged from 0.4 to 0.7, suggesting the effects of strong selection by the driver. In addition, our results show that the driver and sensitivity of responders in the Trinidad populations are highly polymorphic. Continued studies of the dynamics of the M-D system in natural populations are critical to considerations of its use in population replacement.

Fitness effects of X chromosome drive in the stalk-eyed fly, Cyrtodiopsis dalmanni

4271
Wilkinson, GSJ, P. M.; Kelleher, E. S.; Muscedere, M. L.; Lorsong, A.,  Journal of Evolutionary Biology,  19:1851-1860. 2006-01-09 00:00:00.
Sex-ratio (SR) males produce predominantly female progeny because most Y chromosome sperm are rendered nonfunctional. The resulting transmission advantage of X-SR chromosomes should eventually cause population extinction unless segregation distortion is masked by suppressors or balanced by selection. By screening male stalk-eyed flies, Cyrtodiopsis dalmanni, for brood sex ratio we found unique SR alleles at three X-linked microsatellite loci and used them to determine if SR persists as a balanced polymorphism. We found that X-SR/X-ST females produced more offspring than other genotypes and that SR males had lower sperm precedence and exhibited lower fertility when mating eight females in 24 h. Adult survival was independent of SR genotype but positively correlated with eye span. We infer that the SR polymorphism is likely maintained by a combination of weak overdominance for female fecundity and frequency dependent selection acting on male fertility. Our discovery of two SR haplotypes in the same population in a 10-year period further suggests that this SR polymorphism may be evolving rapidly.

Segregation distortion in Arabidopsis C24/Col-0 and Col-0/C24 recombinant inbred line populations is due to reduced fertility caused by epistatic interaction of two loci

4270
Torjek, OW-W, H.; Meyer, R. C.; von Korff, M.; Kusterer, B.; Rautengarten, C.; Altmann, T.,  Theoretical and Applied Genetics,  113:1551-1561. 2006-01-08 00:00:00.
A new large set of reciprocal recombinant inbred lines (RILs) was created between the Arabidopsis accessions Col-0 and C24 for quantitative trait mapping approaches, consisting of 209 Col-0 x C24 and 214 C24 x Col-0 F-7 RI lines. Genotyping was performed using 110 evenly distributed framework single nucleotide polymorphism markers, yielding a genetic map of 425.70 cM, with an average interval of 3.87 cM. Segregation distortion (SD) was observed in several genomic regions during the construction of the genetic map. Linkage disequilibrium analysis revealed an association between a distorted region at the bottom of chromosome V and a non-distorted region on chromosome IV. A detailed analysis of the RILs for these two regions showed that an SD occurred when homozygous Col-0 alleles on chromosome IV coincided with homozygous C24 alleles at the bottom of chromosome V. Using nearly isogenic lines segregating for the distorted region we confirmed that this genotypic composition leads to reduced fertility and fitness.

Gene drive systems for insect disease vectors

4269
Sinkins, SPG, F.,  Nature Reviews Genetics,  7:427-435. 2006-01-07 00:00:00.
The elegant mechanisms by which naturally occurring selfish genetic elements, such as transposable elements, meiotic drive genes, homing endonuclease genes and Wolbachia, spread at the expense of their hosts provide some of the most fascinating and remarkable subjects in evolutionary genetics. These elements also have enormous untapped potential to be used in the control of some of the world's most devastating diseases. Effective gene drive systems for spreading genes that can block the transmission of insect-borne pathogens are much needed. Here we explore the potential of natural gene drive systems and discuss the artificial constructs that could be envisaged for this purpose.

A model describing the effect of sex-reversed YY fish in an established wild population: The use of a Trojan Y chromosome to cause extinction of an introduced exotic species

11545
J. B. Gutierrez and J. L. Teem,  Journal of Theoretical Biology,  241:333-341. 2006-01-06 17:28:07.
A novel means of inducing extinction of an exotic fish population is proposed using a genetic approach to shift the ratio of male to females within a population. In the proposed strategy, sex-reversed fish containing two Y chromosomes are introduced into a normal fish population. These YY fish result in the production of a disproportionate number of male fish in subsequent generations. Mathematical modeling of the system following introduction of YY fish at a constant rate reveals that female fish decline in numbers over time, leading to eventual extinction of the population. (c) 2005 Elsevier Ltd. All rights reserved.

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