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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Gene drive overdrive

4110
DeFrancesco, L,  Nature Biotechnology,  33:1019-1021. 2015-01-08 00:00:00.
The recent publication of a simple procedure for creating a CRISPR-Cas9-mediated gene drive has some researchers sounding the alarm. What are the risks to populations in the wild and what precautions are necessary? Laura DeFrancesco investigates.

Muddled genetic terms miss and mess the message

Vihinen, M,  Trends in Genetics,  31:423-425. 2015-01-08 00:00:00.
A critical aspect of science is the clear communication of complicated matters. However, language is often ambiguous, and the message can get lost in the telling. In particular, genetic terms can have different meanings for different people. Here, I discuss this problem and suggest remedies to clarify the message.

Modeling the manipulation of natural populations by the mutagenic chain reaction

4129
Unckless, RLM, P. W.; Connallon, T.; Clark, A. G.,  Genetics,  201:425-431. 2015-01-07 00:00:00.
The use of recombinant genetic technologies for population manipulation has mostly remained an abstract idea due to the lack of a suitable means to drive novel gene constructs to high frequency in populations. Recently Gantz and Bier showed that the use of CRISPR/Cas9 technology could provide an artificial drive mechanism, the so-called mutagenic chain reaction (MCR), which could lead to rapid fixation of even a deleterious introduced allele. We establish the near equivalence of this system to other gene drive models and review the results of simple models showing that, when there is a fitness cost to the MCR allele, an internal equilibrium may exist that is usually unstable. In this case, introductions must be at a frequency above this critical point for the successful invasion of the MCR allele. We obtain estimates of fixation and invasion probabilities for the appropriate scenarios. Finally, we discuss how polymorphism in natural populations may introduce sources of natural resistance to MCR invasion. These modeling results have important implications for application of MCR in natural populations.

The next generation of rodent eradications: Innovative technologies and tools to improve species specificity and increase their feasibility on islands

4109
Campbell, KJB, J.; Eason, C. T.; Glen, A. S.; Godwin, J.; Gould, F.; Holmes, N. D.; Howald, G. R.; Madden, F. M.; Ponder, J. B.; Threadgill, D. W.; Wegmann, A. S.; Baxter, G. S.,  Biological Conservation,  185:47-58. 2015-01-07 00:00:00.
Rodents remain one of the most widespread and damaging invasive alien species on islands globally. The current toolbox for insular rodent eradications is reliant on the application of sufficient anticoagulant toxicant into every potential rodent territory across an island. Despite significant advances in the use of these toxicants over recent decades, numerous situations remain where eradication is challenging or not yet feasible. These include islands with significant human populations, unreceptive stakeholder communities, co-occurrence of livestock and domestic animals, or vulnerability of native species. Developments in diverse branches of science, particularly the medical, pharmaceutical, invertebrate pest control, social science, technology and defense fields offer potential insights into the next generation of tools to eradicate rodents from islands. Horizon scanning is a structured process whereby current problems are assessed against potential future solutions. We undertook such an exercise to identify the most promising technologies, techniques and approaches that might be applied to rodent eradications from islands. We highlight a Rattus-specific toxicant, RNA interference as species-specific toxicants, rodenticide research, crab deterrent in baits, prophylactic treatment for protection of non-target species, transgenic rodents, virus vectored immunocontraception, drones, self-resetting traps and toxicant applicators, detection probability models and improved stakeholder community engagement methods. We present a brief description of each method, and discuss its application to rodent eradication on islands, knowledge gaps, challenges, whether it is incremental or transformative in nature and provide a potential time-line for availability. We outline how a combination of new tools may render previously intractable rodent eradication problems feasible. (C) 2014 Elsevier Ltd. All rights reserved.

Origin, evolution, and population genetics of the selfish Segregation Distorter gene duplication in European and African populations of Drosophila melanogaster

4108
Brand, CLL, A. M.; Presgraves, D. C.,  Evolution,  69:1271-1283. 2015-01-06 00:00:00.
Meiotic drive elements are a special class of evolutionarily selfish genes that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruit fly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene Ran-GTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1-5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations.

Sex-ratio meiotic drive and Y-linked resistance in Drosophila affinis

4128
Unckless, RLL, A. M.; Clark, A. G.,  Genetics,  199:831-840. 2015-01-06 00:00:00.
Genetic elements that cheat Mendelian segregation by biasing transmission in their favor gain a significant fitness benefit. Several examples of sex-ratio meiotic drive, where one sex chromosome biases its own transmission at the cost of the opposite sex chromosome, exist in animals and plants. While the distorting sex chromosome gains a significant advantage by biasing sex ratio, the autosomes, and especially the opposite sex chromosome, experience strong selection to resist this transmission bias. In most wellstudied sex-ratio meiotic drive systems, autosomal and/or Y-linked resistance has been identified. We specifically surveyed for Y-linked resistance to sex-ratio meiotic drive in Drosophila affinis by scoring the sex ratio of offspring sired by males with a driving X and one of several Y chromosomes. Two distinct types of resistance were identified: a restoration to 50/50 sex ratios and a complete reversal of sex ratio to all sons. We confirmed that fathers siring all sons lacked a Y chromosome, consistent with previously published work. Considerable variation in Y-chromosome morphology exists in D. affinis, but we showed that morphology does not appear to be associated with resistance to sex-ratio meiotic drive. We then used two X chromosomes (driving and standard) and three Y chromosomes (susceptible, resistant, and lacking) to examine fertility effects of all possible combinations. We find that both the driving X and resistant and lacking Y have significant fertility defects manifested in microscopic examination of testes and a 48-hr sperm depletion assay. Maintenance of variation in this sex-ratio meiotic drive system, including both the X-linked distorter and the Y-resistant effects, appear to be mediated by a complex interaction between fertility fitness and transmission dynamics.

On the origin of sex chromosomes from meiotic drive

4127
Ubeda, FP, M. M.; Wild, G.,  Proceedings of the Royal Society B-Biological Sciences,  282:20141932. 2015-01-05 00:00:00.
Most animals and many plants make use of specialized chromosomes (sex chromosomes) to determine an individual's sex. Best known are the XY and ZW sex-determination systems. Despite having evolved numerous times, sex chromosomes present something of an evolutionary puzzle. At their origin, alleles that dictate development as one sex or the other (primitive sex chromosomes) face a selective penalty, as they will be found more often in the more abundant sex. How is it possible that primitive sex chromosomes overcome this disadvantage? Any theory for the origin of sex chromosomes must identify the benefit that outweighs this cost and enables a sex-determining mutation to establish in the population. Here we show that a new sex-determining allele succeeds when linked to a sex-specific meiotic driver. The new sex-determining allele benefits from confining the driving allele to the sex in which it gains the benefit of drive. Our model requires few special assumptions and is sufficiently general to apply to the evolution of sex chromosomes in outbreeding cosexual or dioecious species. We highlight predictions of the model that can discriminate between this and previous theories of sex-chromosome origins.

Safeguarding gene drive experiments in the laboratory

4107
Akbari, OSB, H. J.; Bier, E.; Bullock, S. L.; Burt, A.; Church, G. M.; Cook, K. R.; Duchek, P.; Edwards, O. R.; Esvelt, K. M.; Gantz, V. M.; Golic, K. G.; Gratz, S. J.; Harrison, M. M.; Hayes, K. R.; James, A. A.; Kaufman, T. C.; Knoblich, J.; Malik, H. S.; Matthews, K. A.; O'Connor-Giles, K. M.; Parks, A. L.; Perrimon, N.; Port, F.; Russell, S.; Ueda, R.; Wildonger, J.,  Science,  349:927-929. 2015-01-05 00:00:00.
Gene drive systems promote the spread of genetic elements through populations by assuring they are inherited more often than Mendelian segregation would predict (see the figure). Natural examples of gene drive from Drosophila include sex-ratio meiotic drive, segregation distortion, and replicative transposition. Synthetic drive systems based on selective embryonic lethality or homing endonucleases have been described previously in Drosophila melanogaster (1–3), but they are difficult to build or are limited to transgenic populations. In contrast, RNAguided gene drives based on the CRISPR/Cas9 nuclease can, in principle, be constructed by any laboratory capable of making transgenic organisms (4). They have tremendous potential to address global problems in health, agriculture, and conservation, but their capacity to alter wild populations outside the laboratory demands caution (4–7). Just as researchers working with self-propagating pathogens must ensure that these agents do not escape to the outside world, scientists working in the laboratory with gene drive constructs are responsible for keeping them confined (4, 6, 7).

Detrimental effects of an autosomal selfish genetic element on sperm competitiveness in house mice

4126
Sutter, AL, A. K.,  Proceedings of the Royal Society B-Biological Sciences,  282:1-8. 2015-01-04 00:00:00.
Female multiple mating (polyandry) is widespread across many animal taxa and indirect genetic benefits are a major evolutionary force favouring polyandry. An incentive for polyandry arises when multiple mating leads to sperm competition that disadvantages sperm from genetically inferior mates. A reduction in genetic quality is associated with costly selfish genetic elements (SGEs), and studies in invertebrates have shown that males bearing sex ratio distorting SGEs are worse sperm competitors than wild-type males. We used a vertebrate model species to test whether females can avoid an autosomal SGE, the t haplotype, through polyandry. The t haplotype in house mice exhibits strong drive in t heterozygous males by affecting spermatogenesis and is associated with homozygous in utero lethality. We used controlled matings to test the effect of the t haplotype on sperm competitiveness. Regardless of mating order, t heterozygous males sired only 11% of zygotes when competing against wild-type males, suggesting a very strong effect of the t haplotype on sperm quality. We provide, to our knowledge, the first substantial evidence that polyandry ameliorates the harmful effects of an autosomal SGE arising through genetic incompatibility. We discuss potential mechanisms in our study species and the broader implications for the benefits of polyandry.

Presence of segregation distortion in sheep

4125
Raed, MA,  Research Journal of Biotechnology,  10:87-98. 2015-01-03 00:00:00.
The main objective of this project was the investigation of presence of segregation distortion (SD) and description of other relevant parameters of multilocus genetics in Australian Merino sheep. The SD cases investigated three flocks of 98, 79 and 92 offspring and their DNA-based identified dams and sires. DNA samples were genotyped for 28 microsatellite (MS) markers located on different chromosomes. SD was estimated by studying the paternal segregation of alleles in offspring using a bootstrap procedure. The results showed a high proportion of studied loci which demonstrated significant SD. The results provided additional data which add to the common knowledge that sheep population structure and dynamics are affected by evolutionary forces such as gene flow, selection and many other random factors. These forces were noticed in the three populations. Finally, the results obtained from many loci in this project provided evidence of Mendelian violation. Moreover, they indicated that genes affecting male-related SD are spread over the genome.

Systematic evaluation of Drosophila CRISPR tools reveals safe and robust alternatives to autonomous gene drives in basic research

4124
Port, FM, N.; Bullock, S. L.,  G3-Genes Genomes Genetics,  5:1493-1502. 2015-01-02 00:00:00.
The Clustered Regularly Interspaced Short Palindromic Repeat/CRISPR associated (CRISPR/Cas) technology allows rapid, site-specific genome modification in a wide variety of organisms. Proof-of-principle studies in Drosophila melanogaster have used various CRISPR/Cas tools and experimental designs, leading to significant uncertainty in the community about how to put this technology into practice. Moreover, it is unclear what proportion of genomic target sites can be modified with high efficiency. Here, we address these issues by systematically evaluating available CRISPR/Cas reagents and methods in Drosophila. Our findings allow evidence-based choices of Cas9 sources and strategies for generating knock-in alleles. We perform gene editing at a large number of target sites using a highly active Cas9 line and a collection of transgenic gRNA strains. The vast majority of target sites can be mutated with remarkable efficiency using these tools. We contrast our method to recently developed autonomous gene drive technology for somatic and germline genome engineering and conclude that optimized CRISPR with independent transgenes is as efficient, more versatile, and does not represent a biosafety risk.

Genetic Control of Mosquitoes.

5597
Alphey, L.,  Annual Review of Entomology,  59:205-224. 2014-12-17 15:50:24.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.

Sperm traits of masculinized fish relative to wild-type males: a systematic review and meta-analyses

11512
A. M. Senior, S. L. Johnson and S. Nakagawa,  Fish and Fisheries,  17:143-164. 2014-09-11 15:29:18.
Environmental sex reversal (ESR), whereby environmental effects (e.g. exogenous chemicals) override genetic sex determination, is a commonly used technique in aquaculture and physiology research. We performed a systematic review and meta-analyses of the literature that compares the sperm characteristics of masculinized genotypic females to wild-type males. We detected no mean differences between the ejaculate volume, sperm motility, duration or linearity of each type of male. We found some large mean differences in sperm concentration (d=2.541, CI=-0.004 to 5.086), reproductive success (d=-1.400, CI=-2.943 to 0.142), semen osmolality (d=1.850, CI=0.622 to 3.077) and sperm velocity (d=-0.933, CI=-1.426 to -0.441); in the case of the latter two traits, the mean effect was statistically significant. However, any significance did not stand up to a more conservative analysis. Additionally, heterogeneity was high and we found that where large differences between the sperm of sex-reversed and wild-type males are reported, these effects are attributable to sperm sampling methodology. Overall, we found little evidence for large systematic differences between the sperm produced by masculinized and wild-type male fish. Thus, masculinized genotypic females may enjoy reproductive success comparable to genotypic males. This conclusion leads to two potential implications: (i) sex-reversed fish may influence the dynamics of wild populations and (ii) aquaculture practices may use ESR to produce males with sperm quality similar to that of genotypic males. Most studies appear to have been performed in aquaculture species (i.e. Salmonidae); thus future experiments in non-model organisms may provide important insights in to the uniformity of the effects described.

Perceptions and recommendations by scientists for a potential release of genetically modified mosquitoes in Nigeria

12394
P. N. Okorie, J. M. Marshall, O. M. Akpa and O. G. Ademowo,  Malaria Journal,  13:154. 2014-04-23 18:22:17.
The use of genetically modified mosquitoes (GMMs) for the control of malaria and other mosquito-borne diseases has been proposed in malaria-endemic countries, such as Nigeria, which has the largest burden in Africa. Scientists are major stakeholders whose opinions and perceptions can adversely affect the success of the trials of GMMs if they are not involved early. Unfortunately, information on the awareness of Nigerians scientists and their overall perception of the GMMs is practically non-existent in the literature. Therefore, this study aimed at understanding how receptive Nigerian scientists are to a potential release of GMMs for the control of malaria.

The Impact of Pyrethroid Resistance on the Efficacy of Insecticide-Treated Bed Nets against African Anopheline Mosquitoes: Systematic Review and Meta-Analysis.

12678
C. Strode, S. Donegan, P. Garner, A. A. Enayati and J. Hemingway,  PLOS Medicine,  11:e1001619. 2014-03-18 17:48:58.
This meta-analysis found that ITNs are more effective than UTNs regardless of resistance. There appears to be a relationship between resistance and the RD for mosquito mortality in laboratory and field studies. However, the substantive heterogeneity in the studies' results and design may mask the true relationship between resistance and the RD, and the results need to be interpreted with caution. Our analysis suggests the potential for cumulative meta-analysis in entomological trials, but further field research in this area will require specialists in the field to work together to improve the quality of trials, and to standardise designs, assessment, and reporting of both resistance and entomological outcomes.

A critical component of meiotic drive in Neurospora is located near a chromosome rearrangement

4143
Harvey, AMR, D. G.; Groskreutz, K. M.; Kuntz, D. R.; Sharp, K. J.; Shiu, P. K. T.; Hammond, T. M.,  Genetics,  197:1165-1179. 2014-01-21 00:00:00.
Neurospora fungi harbor a group of meiotic drive elements known as Spore killers (Sk). Spore killer-2 (Sk-2) and Spore killer-3 (Sk-3) are two Sk elements that map to a region of suppressed recombination. Although this recombination block is limited to crosses between Sk and Sk-sensitive (Sk(S)) strains, its existence has hindered Sk characterization. Here we report the circumvention of this obstacle by combining a classical genetic screen with next-generation sequencing technology and three-point crossing assays. This approach has allowed us to identify a novel locus called rfk-1, mutation of which disrupts spore killing by Sk-2. We have mapped rfk-1 to a 45-kb region near the right border of the Sk-2 element, a location that also harbors an 11-kb insertion (Sk-2(INS1)) and part of a >220-kb inversion (Sk-2(INV1)). These are the first two chromosome rearrangements to be formally identified in a Neurospora Sk element, providing evidence that they are at least partially responsible for Sk-based recombination suppression. Additionally, the proximity of these chromosome rearrangements to rfk-1 (a critical component of the spore-killing mechanism) suggests that they have played a key role in the evolution of meiotic drive in Neurospora.

Genes that bias Mendelian segregation

4142
Grognet, PL, H.; Malagnac, F.; Silar, P.,  PLOS Genetics,  10:e1004387. 2014-01-20 00:00:00.
Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.

Genome rearrangements and pervasive meiotic drive cause hybrid infertility in fission yeast

4162
Zanders, SEE, M. T.; Yu, J. S.; Kang, J. W.; Fowler, K. R.; Smith, G. R.; Malik, H. S.,  eLife,  3:e02630. 2014-01-20 00:00:00.
Hybrid sterility is one of the earliest postzygotic isolating mechanisms to evolve between two recently diverged species. Here we identify causes underlying hybrid infertility of two recently diverged fission yeast species Schizosaccharomyces pombe and S. kambucha, which mate to form viable hybrid diploids that efficiently complete meiosis, but generate few viable gametes. We find that chromosomal rearrangements and related recombination defects are major but not sole causes of hybrid infertility. At least three distinct meiotic drive alleles, one on each S. kambucha chromosome, independently contribute to hybrid infertility by causing nonrandom spore death. Two of these driving loci are linked by a chromosomal translocation and thus constitute a novel type of paired meiotic drive complex. Our study reveals how quickly multiple barriers to fertility can arise. In addition, it provides further support for models in which genetic conflicts, such as those caused by meiotic drive alleles, can drive speciation.

Dynamics of a combined medea-underdominant population transformation system

4141
Gokhale, CSR, R. G.; Reed, F. A.,  BMC Evolutionary Biology,  14:98. 2014-01-19 00:00:00.
: Transgenic constructs intended to be stably established at high frequencies in wild populations have been demonstrated to "drive" from low frequencies in experimental insect populations. Linking such population transformation constructs to genes which render them unable to transmit pathogens could eventually be used to stop the spread of vector-borne diseases like malaria and dengue. Results: Generally, population transformation constructs with only a single transgenic drive mechanism have been envisioned. Using a theoretical modelling approach we describe the predicted properties of a construct combining autosomal Medea and underdominant population transformation systems. We show that when combined they can exhibit synergistic properties which in broad circumstances surpass those of the single systems. Conclusion: With combined systems, intentional population transformation and its reversal can be achieved readily. Combined constructs also enhance the capacity to geographically restrict transgenic constructs to targeted populations. It is anticipated that these properties are likely to be of particular value in attracting regulatory approval and public acceptance of this novel technology.

Segregation distortion affected by transgenes in early generations of rice crop-weed hybrid progeny: Implications for assessing potential evolutionary impacts from transgene flow into wild relatives

4161
Yang, CW, Z.; Yang, X.; Lu, B. R.,  Journal of Systematics and Evolution,  52:466-476. 2014-01-19 00:00:00.
The significant role of segregation distortion as a driving force of evolution has increasingly gained recognition worldwide. Segregation distortion of parental alleles is commonly reported in hybrid progeny between crops and wild relative species, which possibly influences the evolution potential of the hybrid progeny. Whether transgene introgression into wild and weedy populations through repeated hybridization causes changes of segregation distortion of parental alleles in hybrid progeny is an important question to be addressed to understand the long-term evolution potential of the populations that have received transgenes. To study the influence of a transgene on allelic segregation, we examined gene and genotype frequencies in transgenic and non-transgenic populations of F-3 and F-4 lineages derived from hybrids between transgenic insect-resistant rice (Bt/CpTI) and weedy rice, involving randomly selected 25 simple sequence repeat markers with polymorphisms between the two parents. We found that the transgenes can significantly alter the segregation distortion pattern in hybrid progeny, particularly the direction of segregation deviated to different parents. In transgenic F-3 and F-4 populations, there are approximately 64% and 77% simple sequence repeat loci, respectively, with alleles deviated significantly to the insect-resistant cultivated rice parent; whereas, in non-transgenic F-3 and F-4 populations, approximately 68% and 58% loci, respectively, deviated significantly to the weedy rice parent. Transgenes with strong selection advantages may have evolutionary impacts on hybrid progeny by changing their pattern of allelic segregation distortion after introgression from transgenic crops to wild relatives through hybridization.

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