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.


An Initial Framework for the Environmental Risk Assessment of Synthetic Biology-Derived Organisms with a Focus on Gene Drives.

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W. G. Landis, E. A. Brown and S. Eikenbary,  Synthetic Biology 2020: Frontiers in Risk Analysis and Governance. Risk, Systems and Decisions.,  2019-11-29 17:16:37.
We apply the structure of source-stressor-habitat-effect-impact pathway derived from the relative risk model (Landis and Wiegers 2005) and as was demonstrated to be applicable in the National Academy of Sciences, Engineering and Medicine (NASEM) 2016 report Gene Drives on the Horizon. This relative risk model is now calculated employing Bayesian networks and has been applied to forestry management (Ayre and Landis 2012), infectious disease (Ayre et al. 2014), invasive species (Herring et al. 2015), contaminated sites (Landis et al. 2017a; Johns et al. 2017), and watershed management (Hines and Landis 2014; Graham et al. 2019).

An X-linked meiotic drive allele has strong, recessive fitness costs in female Drosophila pseudoobscura

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W. Larner, T. Price, L. Holman and N. Wedell,  Proceedings of the Royal Society B-Biological Sciences,  286:9. 2019-11-27 18:44:20.
Selfish 'meiotic drive' alleles are transmitted to more than 50% of offspring, allowing them to rapidly invade populations even if they reduce the fitness of individuals carrying them. Theory predicts that drivers should either fix or go extinct, yet some drivers defy these predictions by persisting at low, stable frequencies for decades. One possible explanation for this discrepancy is that drivers are especially costly when homozygous, although empirical tests of this idea are rare and equivocal. Here, we measure the fitness of female Drosophila pseudoobscura carrying zero, one or two copies of the X-linked driver sex ratio (SR). SR had strong negative effects on female offspring production and the probability of reproductive failure, and these effects were largely similar across four genetic backgrounds. SR was especially costly when homozygous. We used our fitness measurements to parametrize a population genetic model, and found that the female fitness costs observed here can explain the puzzlingly low allele frequency of SR in nature. We also use the model to show how spatial variation in female mating behaviour, fitness costs of SR and the reduced siring success of SR males can jointly explain the north-south cline in SR frequencies across North America.

Establishment of Wolbachia Strain wAlbB in Malaysian Populations of Aedes aegypti for Dengue Control

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W. A. Nazni, A. A. Hoffmann, A. NoorAfizah, Y. L. Cheong, M. V. Mancini, N. Golding, G. M. R. Kamarul, M. A. K. Arif, H. Thohir, H. NurSyamimi, M. Z. ZatilAqmar, M. NurRuqqayah, A. NorSyazwani, A. Faiz, F.-R. M. N. Irfan, S. Rubaaini, N. Nuradila, N. M. N,  Current Biology,  29:4241-4248.e5. 2019-11-21 15:20:44.
Dengue has enormous health impacts globally. A novel approach to decrease dengue incidence involves the introduction of Wolbachia endosymbionts that block dengue virus transmission into populations of the primary vector mosquito, Aedes aegypti. The wMel Wolbachia strain has previously been trialed in open releases of Ae. aegypti; however, the wAlbB strain has been shown to maintain higher density than wMel at high larval rearing temperatures. Releases of Ae. aegypti mosquitoes carrying wAlbB were carried out in 6 diverse sites in greater Kuala Lumpur, Malaysia, with high endemic dengue transmission. The strain was successfully established and maintained at very high population frequency at some sites or persisted with additional releases following fluctuations at other sites. Based on passive case monitoring, reduced human dengue incidence was observed in the release sites when compared to control sites. The wAlbB strain of Wolbachia provides a promising option as a tool for dengue control, particularly in very hot climates.

The Competitive Mating of Irradiated Brown Marmorated Stink Bugs, Halyomorpha halys, for the Sterile Insect Technique

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D. M. Suckling, M. Cristofaro, G. Roselli, M. C. Levy, A. Cemmi, V. Mazzoni, L. D. Stringer, V. Zeni, C. Ioriatti and G. Anfora,  Insects,  10. 2019-11-16 15:14:41.
The sterility of eggs and nymphs from gamma-irradiated male Halyomorpha halys was investigated to determine the potential for the sterile insect technique (SIT). Males irradiated at 0, 16, 24 and 32 Gy were placed with untreated virgin females, and egg sterility was determined, showing 54.3% at 16 Gy. The percentage of sterility from irradiation was 26 percent lower than previous results from the USA and the variance was very high. Competitive overflooding ratio trials between irradiated virgin males and fertile virgin males at a 5:1 ratio resulted in the expected egg sterility, indicating competitive performance by irradiated males. By July and August, older, irradiated overwintered males were significantly less competitive than similar, non-irradiated males. There is a need to revisit the irradiation delivery method to achieve proper precision around the paternal dose required for an expected >80% egg sterility and subsequent ~99% endpoint sterility estimated at adult emergence in the F1 phase. These results suggest that the mating competitiveness and competency of males after irradiation at 16 Gy is not limiting to the sterile insect technique for suppression. A wild harvest of overwintering males using the aggregation pheromone, followed by irradiation and male release, might replace rearing. Mass-collected, sterilized bugs could be transported from an area of high H. halys density and shipped for release to enable suppression or eradication elsewhere. This concept is under development but further work is needed now to understand the difference in results between the US and Italian irradiators and increase the reliability of dosimetry.

Effects of a male meiotic driver on male and female transcriptomes in the house mouse

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A. Lindholm, A. Sutter, S. Kunzel, D. Tautz and H. Rehrauer,  Proceedings of the Royal Society B-Biological Sciences,  286:1-8. 2019-11-13 20:18:05.
Not all genetic loci follow Mendel's rules, and the evolutionary consequences of this are not yet fully known. Genomic conflict involving multiple loci is a likely outcome, as restoration of Mendelian inheritance patterns will be selected for, and sexual conflict may also arise when sexes are differentially affected. Here, we investigate effects of the t haplotype, an autosomal male meiotic driver in house mice, on genome-wide gene expression patterns in males and females. We analysed gonads, liver and brain in adult same-sex sibling pairs differing in genotype, allowing us to identify t-associated differences in gene regulation. In testes, only 40% of differentially expressed genes mapped to the approximately 708 annotated genes comprising the t haplotype. Thus, much of the activity of the t haplotype occurs in trans, and as upregulation. Sperm maturation functions were enriched among both cis and trans acting t haplotype genes. Within the t haplotype, we observed more downregulation and differential exon usage. In ovaries, liver and brain, the majority of expression differences mapped to the t haplotype, and were largely independent of the differences seen in the testis. Overall, we found widespread transcriptional effects of this male meiotic driver in the house mouse genome.

Rodent gene drives for conservation: opportunities and data needs

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J. Godwin, M. Serr, K. Barnhill-Dilling, D. V. Blondel, P. R. Brown, K. Campbell, J. Delborne, A. L. Lloyd, K. P. Oh, T. A. A. Prowse, R. Saah and P. Thomas,  Proceedings of the Royal Society B-Biological Sciences,  286:20191606. 2019-11-10 16:22:06.
Invasive rodents impact biodiversity, human health and food security worldwide. The biodiversity impacts are particularly significant on islands, which are the primary sites of vertebrate extinctions and where we are reaching the limits of current control technologies. Gene drives may represent an effective approach to this challenge, but knowledge gaps remain in a number of areas. This paper is focused on what is currently known about natural and developing synthetic gene drive systems in mice, some key areas where key knowledge gaps exist, findings in a variety of disciplines relevant to those gaps and a brief consideration of how engagement at the regulatory, stakeholder and community levels can accompany and contribute to this effort. Our primary species focus is the house mouse, Mus musculus, as a genetic model system that is also an important invasive pest. Our primary application focus is the development of gene drive systems intended to reduce reproduction and potentially eliminate invasive rodents from islands. Gene drive technologies in rodents have the potential to produce significant benefits for biodiversity conservation, human health and food security. A broad-based, multidisciplinary approach is necessary to assess this potential in a transparent, effective and responsible manner.

The impact of local population genetic background on the spread of the selfish element Medea-1 in red flour beetles

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S. A. Cash, M. A. Robert, M. D. Lorenzen and F. Gould,  Ecology and Evolution,  12:1-12. 2019-11-10 16:06:41.
Selfish genetic elements have been found in the genomes of many species, yet our understanding of their evolutionary dynamics is only partially understood. A number of distinct selfish Medea elements are naturally present in many populations of the red flour beetle (Tribolium castaneum). Although these Medea elements are predicted by models to increase in frequency within populations because any offspring of a Medea-bearing mother that do not inherit at least one Medea allele will die, experiments demonstrating an increase in a naturally occurring Medea element are lacking. Our survey of the specific Medea element, M-1, in the United States showed that it had a patchy geographic distribution. From the survey, it could not be determined if this distribution was caused by a slow process of M-1 colonization of discrete populations or if some populations lacked M-1 because they had genetic factors conferring resistance to the Medea mechanism. We show that populations with naturally low to intermediate M-1 frequencies likely represent transient states during the process of Medea spread. Furthermore, we find no evidence that genetic factors are excluding M-1 from US populations where the element is not presently found. We also show how a known suppressor of Medea can impair the increase of M-1 in populations and discuss the implications of our findings for pest-management applications of Medea elements.

The distribution and spread of naturally occurring Medea selfish genetic elements in the United States

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S. A. Cash, M. D. Lorenzen and F. Gould,  Ecology and Evolution,  9:14407–14416.. 2019-11-09 16:17:38.
Selfish genetic elements (SGEs) are DNA sequences that are transmitted to viable offspring in greater than Mendelian frequencies. Medea SGEs occur naturally in some populations of red flour beetle (Tribolium castaneum) and are expected to increase in frequency within populations and spread among populations. The large-scale U.S. distributions of Medea-4 (M4) had been mapped based on samples from 1993 to 1995. We sampled beetles in 2011?2014 and show that the distribution of M4 in the United States is dynamic and has shifted southward. By using a genetic marker of Medea-1 (M1), we found five unique geographic clusters with high and low M1 frequencies in a pattern not predicted by microsatellite-based analysis of population structure. Our results indicate the absence of rigid barriers to Medea spread in the United States, so assessment of what factors have limited its current distribution requires further investigation. There is great interest in using synthetic SGEs, including synthetic Medea, to alter or suppress pest populations, but there is concern about unpredicted spread of these SGEs and potential for populations to become resistant to them. The finding of patchy distributions of Medea elements suggests that released synthetic SGEs cannot always be expected to spread uniformly, especially in target species with limited dispersal.

Meiotic drive mechanisms: lessons from Drosophila

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C. Courret, C.-H. Chang, K. H.-C. Wei, C. Montchamp-Moreau and A. M. Larracuente,  Proceedings of the Royal Society B: Biological Sciences,  286:20191430. 2019-10-23 20:28:42.
Meiotic drivers are selfish genetic elements that bias their transmission into gametes, often to the detriment of the rest of the genome. The resulting intragenomic conflicts triggered by meiotic drive create evolutionary arms races and shape genome evolution. The phenomenon of meiotic drive is widespread across taxa but is particularly prominent in the Drosophila genus. Recent studies in Drosophila have provided insights into the genetic origins of drivers and their molecular mechanisms. Here, we review the current literature on mechanisms of drive with an emphasis on sperm killers in Drosophila species. In these systems, meiotic drivers often evolve from gene duplications and targets are generally linked to heterochromatin. While dense in repetitive elements and difficult to study using traditional genetic and genomic approaches, recent work in Drosophila has made progress on the heterochromatic compartment of the genome. Although we still understand little about precise drive mechanisms, studies of male drive systems are converging on common themes such as heterochromatin regulation, small RNA pathways, and nuclear transport pathways. Meiotic drive systems are therefore promising models for discovering fundamental features of gametogenesis.

Does meiotic drive alter male mate preference?

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S. R. Finnegan, L. Nitsche, M. Mondani, M. F. Camus, K. Fowler and A. Pomiankowski,  Behavioral Ecology,  13:194-201. 2019-10-20 14:14:20.
Male mate preferences have been demonstrated across a range of species, including the Malaysian stalk-eyed fly, Teleopsis dalmanni. This species is subject to sex-ratio (SR), an X-linked male meiotic driver, which causes the dysfunction of Y-sperm and the production of all-female broods. While there has been work considering female avoidance of meiotic drive males, the mating decisions of drive-bearing males have not been considered previously. Drive males may be less able to bear the cost of choice as SR is associated with a low-frequency inversion that causes reduced organismal fitness. Drive males may also experience weaker selection for preference maintenance if they are avoided by females. Using binary choice trials, across two experiments, we confirmed male preference for large (fecund) females but found no evidence that the strength of male preference differs between drive and standard males. We showed that large eyespan males displayed strong preference for large females, whereas small eyespan males showed no preference. Taken together, these results suggest that, even though meiotic drive is associated with lower genetic quality, it does not directly interfere with male mate preference among available females. However, as drive males tend to have smaller eyespan (albeit only similar to 5% on average), this will to a minor extent weaken their strength of preference.

Fitness consequences of the selfish supergene Segregation Distorter

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H. W. S. Wong and L. Holman,  Journal of Evolutionary Biology,  33:89-100. 2019-10-11 20:21:24.
Segregation distorters are selfish genetic elements that subvert Mendelian inheritance, often by destroying gametes that do not carry the distorter. Simple theoretical models predict that distorter alleles will either spread to fixation or stabilize at some high intermediate frequency. However, many distorters have substantially lower allele frequencies than predicted by simple models, suggesting that key sources of selection remain to be discovered. Here, we measured the fitness of Drosophila melanogaster adults and juveniles carrying zero, one or two copies of three different variants of the naturally occurring supergene Segregation Distorter (SD), in order to investigate why SD alleles remain relatively rare within populations despite being preferentially inherited. First, we show that the three SD variants differ in the severity and dominance of the fitness costs they impose on individuals carrying them. Second, SD-carrying parents produced less fit offspring in some crosses, independent of offspring genotype, indicating that SD alleles can have nongenetic, transgenerational costs in addition to their direct costs. Third, we found that SD carriers sometimes produce a biased offspring sex ratio, perhaps due to off-target effects of SD on the sex chromosomes. Finally, we used a theoretical model to investigate how sex ratio and transgenerational effects alter the population genetics of distorter alleles; accounting for these additional costs helps to explain why real-world segregation distorter alleles are rarer than predicted.

Evolutionary simulations of Z-linked suppression gene drives

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L. Holman,  Proceedings of the Royal Society B-Biological Sciences,  286:1-9. 2019-10-09 20:23:58.
Synthetic gene drives may soon be used to suppress or eliminate populations of disease vectors, pathogens, invasive species, and agricultural pests. Recent proposals have focused on using Z-linked gene drives to control species with ZW sex determination, which include Lepidopteran pests, parasitic trematodes, and cane toads. These proposals include Z-linked 'W-shredders', which would suppress populations by cleaving the W chromosome and causing females to produce only sons, as well as Z-linked female-sterilizing gene drives. Here, I use eco-evolutionary simulations to evaluate the potential of some proposed Z-linked gene drives, and to produce recommendations regarding their design and use. The simulations show that W-shredders are likely to be highly effective at eradicating populations provided that resistance to W-shredding cannot evolve. However, W-shredder alleles can invade populations from very low frequencies, making it difficult to eliminate specific populations while leaving nearby populations untouched; this issue may restrict their possible uses.

Peri-Urban Community Attitudes towards Codling Moth Trapping and Suppression Using the Sterile Insect Technique in New Zealand

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G. Paterson, G. L. W. Perry, J. T. S. Walker and D. M. Suckling,  Insects,  10. 2019-10-09 15:21:37.
New, more socially-acceptable technologies are being developed to suppress horticultural pests, because suppression is technically difficult with current technologies, especially in urban areas. One technique involves the release of sterile insects to prevent offspring in the next generation. This technology involves aerial or ground release systems, but this could also create issues for the public. This study investigated community perceptions of a recently-introduced response to codling moth control in New Zealand—Sterile Insect Technique (SIT). Community attitudes to SIT were examined in Hastings, New Zealand, in April, 2018. Eighty-six detailed interviews were undertaken with a random sample of households. This community was very willing (98% agreement) to host a sex pheromone trap in their gardens, and condoned regular visits to monitor traps. Attitudes to SIT were very positive (98% in favor). Once explained, the concept of using unmanned aerial vehicles to deliver sterile insects was also acceptable (98%) to the community. Use of unmanned aerial vehicles to release sterile insects during a hypothetical incursion response of an exotic fruit fly was also supported at 98% by respondent householders. Investigation of community attitudes can be valuable to guide practitioners in determining suitable technologies before an area-wide programme is launched.

Efforts to enhance safety measures for CRISPR/Cas-based gene drive technology in Japan

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T. Tanaka, N. Tanaka, Y. Nagano, H. Kanuka, D. S. Yamamoto, N. Yamamoto, E. Nanba and T. Nishiuch,  Journal of Environment and Safety,  2019-10-07 20:47:13.
Gene drive is a powerful system that can spread a desirable genetic trait into an entire species and/or population of a certain region, bypassing Mendelian rules of inheritance. Recently, one of the genome editing technologies, CRISPR/Cas, has been developed, making it easier to use gene drive in many different organisms. However, gene drive has potential risks that impact genetic diversity when organisms produced by CRISPR/Cas-based Gene Drive Technology (CCGDT) are accidentally released; therefore, a high degree of prudence is required when CCGDT is used. In Japan, a Working Group on Gene Drive has been established in the Academic Association for Promotion of Genetic Studies (AAPGS), and a Statement on the Handling of Gene Drive was issued to the public including research institute across Japan, after comprehensive and extensive discussions by the working group in order to reduce risks posed by CCGDT. A national-wide survey on CCGDT was implemented. The survey revealed that those in managerial positions including members and secretariats of institutional review boards on recombinant DNA, and biosafety officers are conscious of CCGDT, and efforts to grasp experimental plans involving CCGDT are made by utilizing an application form for recombinant DNA experiment. In contrast, potential risks of CCGDT are not understood by many researchers. All stakeholders need to disseminate potential risks and preventive measures regarding CCGDT to all researchers who may wish to use this technology. Researchers should use CCGDT upon understanding its potential risks and taking necessary measures. This report refers to how safety measures for CRISPR/Cas-based gene drive technology which has potential risks to ecological system has been discussed and results of national-wide questionnaire survey on gene drive in Japan based on the poster presentation at the Asian Conference on Safety & Education in Laboratory 2018.

Gene Drives: Dynamics and Regulatory Matters-A Report from the Workshop “Evaluation of Spatial and Temporal Control of Gene Drives,” April 4-5, 2019, Vienna

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B. Giese, J. L. Friess, N. H. Barton, P. W. Messer, F. Debarre, M. F. Schetelig, N. Windbichler, H. Meimberg and C. Boete,  Bioessays,  41:3. 2019-10-07 18:26:19.
Gene Drives are regarded as future tools with a high potential for population control. Due to their inherent ability to overcome the rules of Mendelian inheritance, gene drives (GD) may spread genes rapidly through populations of sexually reproducing organisms. A release of organisms carrying a GD would constitute a paradigm shift in the handling of genetically modified organisms because gene drive organisms (GDO) are designed to drive their transgenes into wild populations and thereby increase the number of GDOs. The rapid development in this field and its focus on wild populations demand a prospective risk assessment with a focus on exposure related aspects. Presently, it is unclear how adequate risk management could be guaranteed to limit the spread of GDs in time and space, in order to avoid potential adverse effects in socio‐ecological systems. The recent workshop on the “Evaluation of Spatial and Temporal Control of Gene Drives” hosted by the Institute of Safety/Security and Risk Sciences (ISR) in Vienna aimed at gaining some insight into the potential population dynamic behavior of GDs and appropriate measures of control. Scientists from France, Germany, England, and the USA discussed both topics in this meeting on April 4–5, 2019. This article summarizes results of the workshop.

Two unresolved issues in community engagement for field trials of genetically modified mosquitoes

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D. B. Resnik,  Pathogens and Global Health,  113:238-245. 2019-09-25 19:32:29.
There is an emerging consensus among scientists, ethicists, and public health officials that substantive and effective engagement with communities and the wider public is required prior to releasing genetically modified mosquitoes into the environment.

Threshold-Dependent Gene Drives in the Wild: Spread, Controllability, and Ecological Uncertainty

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G. A. Backus and J. A. Delborne,  BioScience,  69:900-907. 2019-09-18 16:02:59.
Gene drive technology could allow the intentional spread of a desired gene throughout an entire wild population in relatively few generations. However, there are major concerns that gene drives could either fail to spread or spread without restraint beyond the targeted population. One potential solution is to use more localized threshold-dependent drives, which only spread when they are released in a population above a critical frequency. However, under certain conditions, small changes in gene drive fitness could lead to divergent outcomes in spreading behavior. In the face of ecological uncertainty, the inability to estimate gene drive fitness in a real-world context could prove problematic because gene drives designed to be localized could spread to fixation in neighboring populations if ecological conditions unexpectedly favor the gene drive. This perspective offers guidance to developers and managers because navigating gene drive spread and controllability could be risky without detailed knowledge of ecological contexts.

Mosquito Control

Dye-Braumuller K, Fredregill C, Debboun M.,  Mosquitoes, Communities, and Public Health in Texas,  8:249-278. 2019-09-14 14:00:28.
Globally, mosquito control has evolved over centuries, as humans have learned more about the world’s deadliest animal,that is, the mosquito, and the pathogens they are capable of transmitting. Mosquitoes not only transmit pathogens but also cause severe allergic reactions, intense irritation, and even extensive blood loss to some animals such as livestock. These factors have led to the development of a multitude of techniques and approaches to control mosquitoes throughout centuries. They have been established since Sir Patrick Manson first linked mosquitoes to the transmission of human pathogens when he discovered that the house mosquito harbored and presumably—at that time—was transmitting intermediate larvae of the filarial worm, Wuchereria bancrofti (Manson, 1878; Chernin, 1983; Clements and Harbach, 2017). Due to the wide range of impacts mosquitoes have on humans, large quantities of resources have been dedicated to their control. For example, the United States (US) spends hundreds of millions of dollars to control mosquitoes annually (Foster and Walker, 2009). There were a few major points in US history that led to these expansive control efforts, and the first part of this chapter will describe these milestones

Malaria eradication within a generation: ambitious, achievable, and necessary

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R. G. A. Feachem, I. Chen, O. Akbari, A. Bertozzi-Villa, S. Bhatt, F. Binka, M. F. Boni, C. Buckee, J. Dieleman, A. Dondorp, A. Eapen, N. Sekhri Feachem, S. Filler, P. Gething, R. Gosling, A. Haakenstad, K. Harvard, A. Hatefi, D. Jamison, K. E. Jones, C.,  Lancet,  394:1056-1112. 2019-09-13 15:21:30.
50 years after a noble but flawed attempt to eradicate malaria in the mid-20th century, the global malaria community is once again seriously considering eradication. Momentum towards eradication has been building for decades, and more than half of the world’s countries are now malaria free.

Standard deviations: The biological bases of transmission ratio distortion

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L. Fishman and M. McIntosh,  Annual Review of Genetics,  53:347-372. 2019-09-10 18:59:40.
The rule of Mendelian inheritance is remarkably robust, but deviations from the equal transmission of alternative alleles at a locus [a.k.a. transmission ratio distortion (TRD)] are also commonly observed in genetic mapping populations. Such TRD reveals locus-specific selection acting at some point between the diploid heterozygous parents and progeny genotyping and therefore can provide novel insight into otherwise-hidden genetic and evolutionary processes. Most of the classic selfish genetic elements were discovered through their biasing of transmission, but many unselfish evolutionary and developmental processes can also generate TRD. In this review, we describe methodologies for detecting TRD in mapping populations, detail the arenas and genetic interactions that shape TRD during plant and animal reproduction, and summarize patterns of TRD from across the genetic mapping literature. Finally, we point to new experimental approaches that can accelerate both detection of TRD and characterization of the underlying genetic mechanisms.

Transgenic Aedes aegypti Mosquitoes Transfer Genes into a Natural Population

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B. R. Evans, P. Kotsakiozi, A. L. Costa-da-Silva, R. S. Ioshino, L. Garziera, M. C. Pedrosa, A. Malavasi, J. F. Virginio, M. L. Capurro and J. R. Powell,  Scientific Reports,  9:6. 2019-09-10 15:09:04.
We genotyped the release strain and the target Jacobina population before releases began for >21,000 single nucleotide polymorphisms (SNPs). Genetic sampling from the target population six, 12, and 27-30 months after releases commenced provides clear evidence that portions of the transgenic strain genome have been incorporated into the target population. Evidently, rare viable hybrid offspring between the release strain and the Jacobina population are sufficiently robust to be able to reproduce in nature. The release strain was developed using a strain originally from Cuba, then outcrossed to a Mexican population. Thus, Jacobina Ae. aegypti are now a mix of three populations. It is unclear how this may affect disease transmission or affect other efforts to control these dangerous vectors. These results highlight the importance of having in place a genetic monitoring program during such releases to detect un-anticipated outcomes.

Twenty-five Years of Research Experience with the Sterile Insect Technique and Area-Wide Management of Codling Moth, Cydia pomonella (L.), in Canada

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H. M. A. Thistlewood and G. J. R. Judd,  Insects,  10:292. 2019-09-10 14:21:45.
The advent of novel genetic methods has led to renewed interest in the sterile insect technique (SIT) for management of insect pests, owing to applications in mass rearing and in the production of sterile offspring without use of irradiation. An area-wide management programme for codling moth, Cydia pomonella, has employed the SIT and other management practices over a large area (3395 to 7331 ha) of orchards and neighbouring urban, public, or First Nations lands in British Columbia, Canada, for 25 years. This project is the first to employ the SIT for C. pomonella, and the longest-running application of area-wide techniques for its control, anywhere. It was derived from basic research and applied trials from the 1960s onwards. Many biological challenges were overcome, and lessons learnt, in transferring from small- to large-scale applications of mass rearing and the SIT, with particular regard to Lepidoptera. Research has proven essential to identifying, if not resolving, issues that threaten the implementation and success of any such programme. The major challenges encountered, and the resulting research, are reviewed, as well as future directions. Recommendations are given for application of the SIT as part of any area-wide management programme for C. pomonella.

A 2017 horizon scan of emerging issues for global conservation and biological diversity

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Sutherland, WJB, P.; Broad, S.; Clout, M.; Connor, B.; Cote, I. M.; Dicks, L. V.; Doran, H.; Entwistle, A. C.; Fleishman, E.; Fox, M.; Gaston, K. J.; Gibbons, D. W.; Jiang, Z.; Keim, B.; Lickorish, F. A.; Markillie, P.; Monk, K. A.; Pearce-Higgins, J. W.; Peck, L. S.; Pretty, J.; Spalding, M. D.; Tonneijck, F. H.; Wintle, B. C.; Ockendon, N.,  Trends in Ecology & Evolution,  32:31-40. 2019-09-09 00:00:00.
We present the results of our eighth annual horizon scan of emerging issues likely to affect global biological diversity, the environment, and conservation efforts in the future. The potential effects of these novel issues might not yet be fully recognized or understood by the global conservation community, and the issues can be regarded as both opportunities and risks. A diverse international team with collective expertise in horizon scanning, science communication, and conservation research, practice, and policy reviewed 100 potential issues and identified 15 that qualified as emerging, with potential substantial global effects. These issues include new developments in energy storage and fuel production, sand extraction, potential solutions to combat coral bleaching and invasive marine species, and blockchain technology.

Herbicide resistant weeds: A call to integrate conventional agricultural practices, molecular biology knowledge and new technologies

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V. E. Perotti, A. S. Larran, V. E. Palmieri, A. K. Martinatto and H. R. Permingeat,  Plant Science,  290:110255. 2019-09-06 21:01:14.
Herbicide resistant (HR) weeds are of major concern in modern agriculture. This situation is exacerbated by the massive adoption of herbicide-based technologies along with the overuse of a few active ingredients to control weeds over vast areas year after year. Also, many other anthropological, biological, and environmental factors have defined a higher rate of herbicide resistance evolution in numerous weed species around the world. This review focuses on two central points: 1) how these factors have affected the resistance evolution process; and 2) which cultural practices and new approaches would help to achieve an effective integrated weed management. We claim that global climate change is an unnoticed factor that may be acting on the selection of HR weeds, especially those evolving into non-target-site resistance mechanisms. And we present several new tools –such as Gene Drive and RNAi technologies- that may be adopted to cope with herbicide resistance spread, as well as discuss their potential application at field level. This is the first review that integrates agronomic and molecular knowledge of herbicide resistance. It covers not only the genetic basis of the most relevant resistance mechanisms but also the strengths and weaknesses of traditional and forthcoming agricultural practices.

A natural gene drive system influences bovine tuberculosis susceptibility in African buffalo: Possible implications for disease management

6038
P. van Hooft, W. M. Getz, B. J. Greyling and A. D. S. Bastos,  PLoS One,  14:e0221168. 2019-09-04 20:57:09.
Bovine tuberculosis (BTB) is endemic to the African buffalo (Syncerus caffer) of Hluhluwe-iMfolozi Park (HiP) and Kruger National Park, South Africa. In HiP, the disease has been actively managed since 1999 through a test-and-cull procedure targeting BTB-positive buffalo. Prior studies in Kruger showed associations between microsatellite alleles, BTB and body condition. A sex chromosomal meiotic drive, a form of natural gene drive, was hypothesized to be ultimately responsible. These associations indicate high-frequency occurrence of two types of male-deleterious alleles (or multiple-allele haplotypes). One type negatively affects body condition and BTB resistance in both sexes. The other type has sexually antagonistic effects: negative in males but positive in females. Here, we investigate whether a similar gene drive system is present in HiP buffalo, using 17 autosomal microsatellites and microsatellite-derived Y-chromosomal haplotypes from 401 individuals, culled in 2002–2004. We show that the association between autosomal microsatellite alleles and BTB susceptibility detected in Kruger, is also present in HiP. Further, Y-haplotype frequency dynamics indicated that a sex chromosomal meiotic drive also occurred in HiP. BTB was associated with negative selection of male-deleterious alleles in HiP, unlike positive selection in Kruger. Birth sex ratios were female-biased. We attribute negative selection and female-biased sex ratios in HiP to the absence of a Y-chromosomal sex-ratio distorter. This distorter has been hypothesized to contribute to positive selection of male-deleterious alleles and male-biased birth sex ratios in Kruger. As previously shown in Kruger, microsatellite alleles were only associated with male-deleterious effects in individuals born after wet pre-birth years; a phenomenon attributed to epigenetic modification. We identified two additional allele types: male-specific deleterious and beneficial alleles, with no discernible effect on females. Finally, we discuss how our findings may be used for breeding disease-free buffalo and implementing BTB test-and-cull programs.

Engineered action at a distance: Blood-meal-inducible paralysis in Aedes aegypti

16651
R. E. Haghighat-Khah, T. Harvey-Samuel, S. Basu, O. StJohn, S. Scaife, S. Verkuijl, E. Lovett and L. Alphey,  PLOS Neglected Tropical Diseases,  13:e0007579. 2019-09-03 20:37:29.
Here we demonstrate that it is possible to engineer ‘non-cell autonomous’ effectors–that is where the effect (e.g. the action of a toxic protein) can act on cells distant from the tissues in which they are originally expressed. To achieve this we utilised the endogenous cell secretory pathway to engineer a novel control phenotype–blood-meal inducible (i.e. late-acting, female-specific) reversible paralysis. The logic behind engineering such ‘action at a distance’ phenotypes will extend to a variety of other pest insects and control phenotypes.

Autonomy of Nations and Indigenous Peoples and the Environmental Release of Genetically Engineered Animals with Gene Drives

12398
Z. Meghani,  Global Policy,  10:554-568. 2019-08-05 18:30:26.
This article contends that the environmental release of genetically engineered (GE) animals with heritable traits that are patented will present a challenge to the efforts of nations and indigenous peoples to engage in self-determination. The environmental release of such animals has been proposed on the grounds that they could function as public health tools or as solutions to the problem of agricultural insect pests. This article brings into focus two political-economic-legal problems that would arise with the environmental release of such organisms. To address those challenges, it is proposed that nations considering the environmental release of GE animals must take into account the underlying circumstances and policy failures that motivate arguments for the use of the modified animals. Moreover, countries must recognize that the UN International Covenant on Civil and Political Rights and the UN International Covenant on Economic, Social and Cultural Rights place on them an obligation to ensure that GE animals with patented heritable traits are not released without the substantive consent of the nations or indigenous peoples that could be affected.

Synthetic Biology: Research Needs for Assessing Environmental Impacts

17467
C. M. Warner, S. R. Carter, R. F. Lance, F. H. Crocker, H. N. Meeks, B. L. Adams, M. L. Magnuson, T. Rycroft, K. Pokrzywinski and E. J. Perkins,  Synthetic Biology 2020: Frontiers in Risk Analysis and Governance,  2019-08-01 18:23:43.
Synthetic biology and its applications have the potential to greatly improve economic development, public health, environmental stewardship, technological advancement, and many other areas. In May 2017, sixty individuals gathered in Lexington, Massachusetts for a workshop sponsored by the U.S. Army Engineer Research and Development Center (ERDC) to discuss applications of synthetic biology with likely or intended interaction with the environment. Representatives from academia, government agencies, industry, and non-governmental organizations convened to identify knowledge gaps and research needs to assess potential environmental impacts from these technologies. The group discussed challenges in environmental risk assessment, regulation, and community engagement for emerging synthetic biology technologies. The workshop was structured around four hypothetical case studies, including the use of gene drive engineered organisms to control infectious disease vectors, engineered microbes for bioremediation, cell-free applications for advanced chemical production, and engineered viruses for water treatment. Meeting these research needs will facilitate appropriate environmental risk assessment and informed decision making for the development and potential deployment of synthetic biology organisms and components in the environment.

Transforming insect population control with precision guided sterile males with demonstration in flies

5905
Kandul, N. P., J. Liu, H. M. Sanchez C, S. L. Wu, J. M. Marshall and O. S. Akbari,  Nature Communications,  10:84. 2019-08-01 16:09:46.
The sterile insect technique (SIT) is an environmentally safe and proven technology to suppress wild populations. To further advance its utility, a novel CRISPR-based technology termed precision guided SIT (pgSIT) is described. PgSIT mechanistically relies on a dominant genetic technology that enables simultaneous sexing and sterilization, facilitating the release of eggs into the environment ensuring only sterile adult males emerge. Importantly, for field applications, the release of eggs will eliminate burdens of manually sexing and sterilizing males, thereby reducing overall effort and increasing scalability. Here, to demonstrate efficacy, we systematically engineer multiple pgSIT systems in Drosophila which consistently give rise to 100% sterile males. Importantly, we demonstrate that pgSIT-generated sterile males are fit and competitive. Using mathematical models, we predict pgSIT will induce substantially greater population suppression than can be achieved by currently-available self-limiting suppression technologies. Taken together, pgSIT offers to potentially transform our ability to control insect agricultural pests and disease vectors.

Viral gene drive in herpesviruses

5917
Walter, M. and E. Verdin,  bioRxiv,  2019:717017. 2019-07-30 16:38:14.
Herpesviruses are ubiquitous pathogens in need of novel therapeutic solutions. Current engineered gene drive strategies rely on sexual reproduction, and are thought to be restricted to sexual organisms. Here, we report on the design of a novel gene drive system that allows the spread of an engineered trait in populations of DNA viruses and, in particular, herpesviruses. We describe the successful transmission of a gene drive sequence between distinct strains of human cytomegalovirus (human herpesvirus 5) and show that gene drive viruses can efficiently target and replace wildtype populations in cell culture experiments. Our results indicate that viral gene drives can be used to suppress a viral infection and may represent a novel therapeutic strategy against herpesviruses.

Combinations of Spok genes create multiple meiotic drivers in Podospora

7240
A. A. Vogan, S. L. Ament-Velásquez, A. Granger-Farbos, J. Svedberg, E. Bastiaans, A. J. M. Debets, V. Coustou, H. Yvanne, C. Clavé, S. J. Saupe and H. Johannesson,  eLife,  8:e46454. 2019-07-26 15:53:58.
Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the Spok gene family underlies the Psks. The combination of Spok genes at different chromosomal locations defines the spore killer types and creates a killing hierarchy within a population. We identify two novel Spok homologs located within a large (74–167 kbp) region (the Spok block) that resides in different chromosomal locations in different strains. We confirm that the SPOK protein performs both killing and resistance functions and show that these activities are dependent on distinct domains, a predicted nuclease and kinase domain. Genomic and phylogenetic analyses across ascomycetes suggest that the Spok genes disperse through cross-species transfer, and evolve by duplication and diversification within lineages.

A family of killers

7238
M. De Carvalho and S. E. Zanders,  eLife,  8:e49211. 2019-07-26 15:50:06.
Spok genes are meiotic drivers that increase their own chances of transmission by killing gametes that do not inherit them.

Assessment of a split homing based gene drive for efficient knockout of multiple genes

5915
Kandul, N. P., J. Liu, A. Buchman, V. M. Gantz, E. Bier and O. S. Akbari,  bioRxiv,  2019:706929. 2019-07-18 16:34:25.
Homing based gene drives (HGD) possess the potential to spread linked cargo genes into natural populations and are poised to revolutionize population control of animals. Given that host-encoded genes have been identified that are important for pathogen transmission, targeting these genes using guide RNAs as cargo genes linked to drives may provide a robust method to prevent transmission. However, effectiveness of the inclusion of additional guide RNAs that target separate host encoded genes has not been thoroughly explored. To test this approach, here we generated a split-HGD in Drosophila melanogaster that encoded a drive linked effector consisting of a second gRNA engineered to target a separate host encoded gene, which we term a gRNA-mediated effector (GME). This design enabled us to assess homing and knockout efficiencies of two target genes simultaneously, and also explore the timing and tissue specificity of Cas9 expression on cleavage/homing rates. We demonstrate that inclusion of a GME can result in high efficiency of disruption of its target gene during super-Mendelian propagation of split-HGD. However, maternal deposition and embryonic expression of Cas9 resulted in the generation of drive resistant alleles which can accumulate and limit the spread of such a drive. Alternative design principles are discussed that could mitigate the accumulation of resistance alleles while incorporating a GME.

Incompatible and sterile insect techniques combined eliminate mosquitoes

16263
X. Zheng, D. Zhang, Y. Li, C. Yang, Y. Wu, X. Liang, Y. Liang, X. Pan, L. Hu, Q. Sun, X. Wang, Y. Wei, J. Zhu, W. Qian, Z. Yan, A. G. Parker, J. R. L. Gilles, K. Bourtzis, J. Bouyer, M. Tang, B. Zheng, J. Yu, J. Liu, J. Zhuang, Z. Hu, M. Zhang, J.-T. Gon,  572,  56-61. 2019-07-17 16:15:33.
Here we show that combining incompatible and sterile insect techniques (IIT–SIT) enables near elimination of field populations of the world’s most invasive mosquito species, Aedes albopictus. Millions of factory-reared adult males with an artificial triple-Wolbachia infection were released, with prior pupal irradiation of the released mosquitoes to prevent unintentionally released triply infected females from successfully reproducing in the field. This successful field trial demonstrates the feasibility of area-wide application of combined IIT–SIT for mosquito vector control.

The potential of genomics for restoring ecosystems and biodiversity

13616
M. F. Breed, P. A. Harrison, C. Blyth, M. Byrne, V. Gaget, N. J. C. Gellie, S. V. C. Groom, R. Hodgson, J. G. Mills, T. A. A. Prowse, D. A. Steane and J. J. Mohr,  Nature Reviews Genetics,  20:615-628. 2019-07-12 13:13:41.
Existing and emerging genomics tools offer the potential to improve the odds of achieving these targets. These tools include population genomics that can improve seed sourcing, meta-omics that can improve assessment and monitoring of restoration outcomes, and genome editing that can generate novel genotypes for restoring challenging environments.

Sex-ratio meiotic drive shapes the evolution of the Y chromosome in Drosophila simulans

6174
Q. Helleu, C. Courret, D. Ogereau, K. L. Burnham, N. Chaminade, M. Chakir, S. Aulard and C. Montchamp-Moreau,  Molecular Biology and Evolution,  36:2668-2681. 2019-07-10 18:50:56.
The recent emergence and spread of X-linked segregation distorters-called "Paris" system-in the worldwide species Drosophila simulans has elicited the selection of drive-resistant Y chromosomes. Here, we investigate the evolutionary history of 386 Y chromosomes originating from 29 population samples collected over a period of 20 years, showing a wide continuum of phenotypes when tested against the Paris distorters, from high sensitivity to complete resistance (males sire similar to 95% to similar to 40% female progeny). Analyzing around 13 kb of Y-linked gene sequences in a representative subset of nine Y chromosomes, we identified only three polymorphic sites resulting in three haplotypes. Remarkably, one of the haplotypes is associated with resistance. This haplotype is fixed in all samples from Sub-Saharan Africa, the region of origin of the drivers. Exceptionally, with the spread of the drivers in Egypt and Morocco, we were able to record the replacement of the sensitive lineage by the resistant haplotype in real time, within only a few years. In addition, we performed in situ hybridization, using satellite DNA probes, on a subset of 21 Y chromosomes from six locations. In contrast to the low molecular polymorphism, this revealed extensive structural variation suggestive of rapid evolution, either neutral or adaptive. Moreover, our results show that intragenomic conflicts can drive astonishingly rapid replacement of Y chromosomes and suggest that the emergence of Paris segregation distorters in East Africa occurred less than half a century ago.

Interpopulation spread of a parasitic B chromosome is unlikely through males in the grasshopper Eyprepocnemis plorans

6166
M. I. Manrique-Poyato, J. Cabrero, M. D. López-León, F. Perfectti, R. Gómez and J. P. M. Camacho,  Heredity,  124:197-206. 2019-07-08 18:29:07.
The near-neutral model of B chromosome evolution predicts that population invasion is quite fast. To test this prediction, in 1994, we introduced males of the grasshopper Eyprepocnemis plorans from a B-carrying population into a B-lacking population and monitored the evolution of B-chromosome frequency up to 2013. We observed fluctuating very low B frequency across years but, remarkably, the B chromosome introduced (the B2 variant) was found up to 1996 only, whereas the B1 variant was present from 1996 onwards, presumably introduced by fishermen using E. plorans males as bait. Effective introgression of genetic material from the donor population was evidenced by the presence of a satellite DNA on autosome 9 (up to 1999) and the presence of one individual in 2006 showing an ISSR marker profile being highly similar to that found in the donor population. This indicated that the males introduced by us effectively mated with resident females, but donor genes rapidly decreased in frequency after this non-recurrent migration event. Taken together, our results indicated: (i) that the non-recurrent migration event had a slight, transient genetic effect on the recipient population, which was diluted in only a few generations; and (ii) that even with recurrent migration (forced by fishermen) the B chromosome failed to increase in frequency. Bearing in mind that B chromosomes in this species drive through females only, we hypothesize that B chromosomes most likely failed invasion in both migration events because the migrating sex shows no B-drive.

Synthetic Biology and the United Nations

7967
H.-E. Lai, C. Canavan, L. Cameron, S. Moore, M. Danchenko, T. Kuiken, Z. Sekeyová and P. S. Freemont,  Trends in Biotechnology,  37:1146-1151. 2019-06-27 14:42:54.
Synthetic biology is a rapidly emerging interdisciplinary field of science and engineering that aims to redesign living systems through reprogramming genetic information. The field has catalysed global debate among policymakers and publics. Here we describe how synthetic biology relates to these international deliberations, particularly the Convention on Biological Diversity (CBD).

Split-gene drive system provides flexible application for safe laboratory investigation and potential field deployment

13625
V. L. Del Amo, A. L. Bishop, H. M. Sánchez C, J. B. Bennett, X. Feng, J. M. Marshall, E. Bier and V. M. Gantz,  bioRxiv,  684597. 2019-06-27 13:35:03.
CRISPR-based gene drives spread through populations bypassing the dictates of Mendelian genetics, offering a population-engineering tool for tackling vector-borne diseases, managing crop pests, and helping island conservation efforts; unfortunately, current technologies raise safety concerns for unintended gene propagation. Herein, we address this by splitting the two drive components, Cas9 and gRNAs, into separate alleles to form a novel trans-complementing split–gene-drive (tGD) and demonstrate its ability to promote super-Mendelian inheritance of the separate transgenes.

Sex Sorting for Pest Control: It’s Raining Men!

17064
C. Lutrat, D. Giesbrecht, E. Marois, S. Whyard, T. Baldet and J. Bouyer,  Trends in Parasitology,  35:649-662. 2019-06-26 14:04:15.
In the pursuit of better pest- and vector-control strategies, attention returns to an old proven technology, the sterile insect technique (SIT) and related insect population-suppression methods. A major obstacle for any of these approaches that involves the release of sterile males is the separation of males from females during the mass rearing stage, in order to improve the cost-efficiency of these methods and to prevent the release of biting and disease-vectoring females. This review describes recent sex-sorting developments in dipteran flies with an emphasis on assessing the suitability of these methods for large-scale rearing of male vectors for mass release.

Biological control of pests and a social model of animal welfare

16284
A. Mankad, U. Kennedy and L. Carter,  Journal of Environmental Management,  247:313-322. 2019-06-25 17:21:12.
We consider the role of perceived humaneness or, more accurately, animal welfare as it relates to managing invasive species from a scientific and social perspective. In order to highlight and articulate particular nuances and standards across different pest control contexts, we use three case examples (feral cats, wild rabbits, and invasive cane toads) and explore where biological pest control and animal welfare interests intersect.

The association between mitochondrial genetic variation and reduced colony fitness in an invasive wasp

13731
J. Dobelmann, A. Alexander, J. W. Baty, N. J. Gemmell, M. A. M. Gruber, O. Quinn, T. Wenseleers and P. J. Lester,  Molecular Ecology,  28:3324-3338. 2019-06-24 19:25:29.
Despite the mitochondrion's long-recognized role in energy production, mitochondrial DNA (mtDNA) variation commonly found in natural populations was assumed to be effectively neutral. However, variation in mtDNA has now been increasingly linked to phenotypic variation in life history traits and fitness. We examined whether the relative fitness in native and invasive common wasp (Vespula vulgaris) populations in Belgium and New Zealand (NZ), respectively, can be linked to mtDNA variation.

A century of bias in genetics and evolution

6691
L. D. Hurst,  Heredity,  123:33-44. 2019-06-12 17:55:20.
Mendel proposed that the heritable material is particulate and that transmission of alleles is unbiased. An assumption of unbiased transmission was necessary to show how variation can be preserved in the absence of selection, so overturning an early objection to Darwinism. In the second half of the twentieth century, it was widely recognised that even strongly deleterious alleles can invade if they have strongly biased transmission (i.e. strong segregation distortion). The spread of alleles with distorted segregation can explain many curiosities. More recently, the selectionist-neutralist duopoly was broken by the realisation that biased gene conversion can explain phenomena such as mammalian isochore structures. An initial focus on unbiased transmission in 1919, has thus given way to an interest in biased transmission in 2019. A focus on very weak bias is now possible owing to technological advances, although technical biases may put a limit on resolving power. To understand the relevance of weak bias we could profit from having the concept of the effectively Mendelian allele, a companion to the effectively neutral allele. Understanding the implications of unbiased and biased transmission may, I suggest, be a good way to teach evolution so as to avoid psychological biases.

A synthetic male-specific sterilization system using the mammalian pro-apoptotic factor in a malaria vector mosquito

16645
D. S. Yamamoto, M. Sumitani, K. Kasashima, H. Sezutsu, H. Matsuoka and H. Kato,  Scientific Reports,  9:11. 2019-06-03 19:52:01.
We produced a transgenic mosquito line that expresses mouse Bax under the control of this testis-specific promoter. Transgenic mosquito males exhibited aberrant testes without functional sperm and complete sterility, whereas transgenic females maintained normal fecundity. Despite their abnormal testes, the transgenic males maintained normal function of male accessory glands and typical mating behaviour. As a result of mating with these males, females showed refractoriness to further mating. These results suggest that transgenic males induce female sterility via mating. The mosquito is one of the most important disease vectors, and the control of their population benefits global public health.

Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection on Islands: Workshop Report

11581
M. Farooque, S. K. Barnhill-Dilling, J. Shapiro and J. Delborne,  North Carolina State University,  2019-06-01 15:28:38.
The “Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection” workshop was held on the North Carolina State University campus in Raleigh, NC on March 7-8, 2019, aiming to convene a diverse group of stakeholders, scientists, funders, and leaders for an exploration of perspectives on the development of a gene drive mouse for restoring biodiversity on islands. Information collected at the workshop is presented in this report to inform upcoming decisions by the NCSU-Safe Genes research team about research, testing, and potential deployment of technologies (the Safe Genes program does not fund any environmental releases of gene drive modified organisms), as well as future engagement activities.

Gene Drives: A report on their science, applications, social aspects, ethics and regulations

6670
H. Dressel,  Critical Scientists Switzerland; European Network of Scientists for Social and Environmental Responsibility; Vereinigung Deutscher Wissenschaftler,  2019-05-17 18:00:50.
Engineered Gene Drives are a new form of genetic modification that provides the tools for permanently modifying or potentially even eradicating species or populations in the wild. Unlike the previous genetically modified organisms (GMOs), gene drive organisms (GDOs) are not meant to stay where they are released, but instead are designed and purpose-built to spread and to drive their modified genes far and wide into wild populations.

Gene drives and the international biodiversity regime

18784
F. Rabitz,  Review of European, Comparative & International Environmental Law,  2019-05-17 17:30:54.
Gene drives are genetic modifications designed for rapidly diffusing traits throughout a target population. They are currently being proposed as biological control agents to combat, for instance, invasive alien species and disease vectors. They also raise concerns regarding their potential adverse effects on biological diversity. This text assesses gene drive governance under the Convention on Biological Diversity (CBD) and its Cartagena Protocol on Biosafety. While gene drives are directly relevant for the objectives of both agreements, their regulatory frameworks have not kept up with the pace of technological change. The focus of this article is on the analysis of gaps and inconsistencies within both agreements. It highlights numerous elements of the CBD and the Cartagena Protocol that raise challenges for gene drive governance, such as matters related to regulatory scope, transboundary movements, precaution and invasive alien species.

Gene-drive-mediated extinction is thwarted by population structure and evolution of sib mating

11202
J. J. Bull, C. H. Remien and S. M. Krone,  Evolution Medicine and Public Health,  2019:66-81. 2019-05-11 14:03:57.
Genetic engineering combined with CRISPR technology has developed to the point that gene drives can, in theory, be engineered to cause extinction in countless species. Success of extinction programs now rests on the possibility of resistance evolution, which is largely unknown. Depending on the gene-drive technology, resistance may take many forms, from mutations in the nuclease target sequence (e.g. for CRISPR) to specific types of non-random population structures that limit the drive (that may block potentially any gene-drive technology).

Improving plant-resistance to insect-pests and pathogens: The new opportunities through targeted genome editing

6176
D. S. Bisht, V. Bhatia and R. Bhattacharya,  Seminars in Cell & Developmental Biology,  96:65-76. 2019-05-08 18:53:44.
The advantages of high input agriculture are fading away due to degenerating soil health and adverse effects of climate change. Safeguarding crop yields in the changing environment and dynamics of pest and pathogens, has posed new challenges to global agriculture. Thus, integration of new technologies in crop improvement has been imperative for achieving the breeding objectives in faster ways. Recently, enormous potential of genome editing through engineered nucleases has been demonstrated in plants. Continuous refinements of the genome editing tools have increased depth and breadth of their applications. So far, genome editing has been demonstrated in more than fifty plant species. These include model species like Arabidopsis, as well as important crops like rice, wheat, maize etc. Particularly, CRISPR/Cas9 based two component genome editing system has been facile with wider applicability. Potential of genome editing has unfurled enormous possibilities for engineering diverse agronomic traits including durable resistance against insect-pests and pathogens. Novel propositions of developing insect and pathogen resistant crops by genome editing include altering the effector-target interaction, knocking out of host-susceptibility genes, engineering synthetic immune receptor eliciting broad spectrum resistance, uncoupling of antagonistic action of defense hormones etc. Alternatively, modification of insect genomes has been used either to create gene drive or to counteract resistance to various insecticides. The distinct advantage of genome editing system is that it can knock out specific target region in the genome without leaving the unwanted vector backbone. In this article, we have reviewed the novel opportunities offered by the genome editing technologies for developing insect and pathogen resistant crop-types, their future prospects and anticipated challenges.

Identification of fk-1;, a Meiotic Driver Undergoing RNA Editing in Neurospora

15131
N. A. Rhoades, A. M. Harvey, D. A. Samarajeewa, J. Svedberg, A. Yusifov, A. Abusharekh, P. Manitchotpisit, D. W. Brown, K. J. Sharp, D. G. Rehard, J. Peters, X. Ostolaza-Maldonado, J. Stephenson, P. K. T. Shiu, H. Johannesson and T. M. Hammond,  Genetics,  212:93. 2019-05-03 16:12:34.
These findings indicate that unedited and edited rfk-1 transcripts exist and that these transcripts could have different roles with respect to the mechanism of meiotic drive by spore killing. Regardless of RNA editing, spore killing only succeeds if rfk-1 transcripts avoid silencing caused by a genome defense process called meiotic silencing by unpaired DNA (MSUD). We show that rfk-1’s MSUD avoidance mechanism is linked to the genomic landscape surrounding the rfk-1 gene, which is located near the Sk-2 border on the right arm of chromosome III. In addition to demonstrating that the location of rfk-1 is critical to spore-killing success, our results add to accumulating evidence that MSUD helps protect Neurospora genomes from complex meiotic drive elements.

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