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.
Mosquito Sexual Selection and Reproductive Control Programs
15921L. J. Cator, C. A. S. Wyer and L. C. Harrington, Trends in Parasitology, 2021-01-06 18:45:40.
Recent work has generated many key insights about specific aspects of mating behavior and physiology. Here, we synthesize these findings and classify swarming mosquito systems as polygynous. Male mating success is highly variable in swarms and evidence suggests that it is likely determined by both scramble competition between males and female choice. Incorporating this new understanding will improve both implementation and long-term stability of reproductive control tools.
Sterile Insect Technique: Principles and Practice in Area-Wide Integrated Pest Management (2nd ed.)
17495V. A. Dyck, J. Hendrichs and A. S. Robinson, CRC Press, 2021-01-06 15:33:05.
For several major insect pests, the environment-friendly sterile insect technique (SIT) is being applied as a component of area-wide integrated pest management (AW-IPM) programmes. This technology, using radiation to sterilize insects, was first developed in the USA, and is currently applied on six continents. For almost six decades it has been a major subject for research and development in the Joint FAO/IAEA Programme on Nuclear Techniques in Food and Agriculture, involving both research and the transfer of this technology to Member States so that they can benefit from improved plant, animal and human health, cleaner environments, increased production of plants and animals in agricultural systems, and accelerated economic development. The socio-economic impacts of AW-IPM programmes that integrate the SIT have confirmed the usefulness of this technology. Numerous publications related to the integration of the SIT in pest management programmes, arising from research, coordinated research projects, field projects, symposia, meetings, and training activities have already provided much information to researchers, pest-control practitioners, programme managers, plant protection and animal health officers, and policy makers. However, by bringing together and presenting in a generic fashion the principles, practice, and global application of the SIT, this book serves as a major reference source for all current and future users of the technology, and also serves as a textbook for academic courses on integrated pest management.
Conservation pest control with new technologies: public perceptions
15913E. A. MacDonald, M. B. Neff, E. Edwards, F. Medvecky and J. Balanovic, Journal of the Royal Society of New Zealand, 2021-01-04 13:45:38.
We conducted eleven focus groups in New Zealand to explore three questions about novel technologies (gene drive and two others for comparison of pest control tools): (1) what are the risks/benefits? (2) how do they compare to current methods? and (3) who should be represented on a panel that evaluates the tools and what factors should they consider?
Whole-genome resequencing reveals loci with allelic transmission ratio distortion in F1 chicken population
16106P. Ren, F. Deng, S. Chen, J. Ran, J. Li, L. Yin, Y. Wang, H. Yin, Q. Zhu and Y. Liu, Molecular Genetics and Genomics, 2021-01-02 15:31:28.
In this study, whole-genome resequencing technology was applied to reveal TRD loci in chicken by constructing a full-sib F1 hybrid population. Through the whole-genome resequencing data of two parents (30 ×) and 38 offspring (5 ×), we detected a total of 2850 TRD SNPs (p-adj < 0.05) located within 400 genes showing TRD, and all of them were unevenly distributed on macrochromosomes and microchromosomes. Our findings suggested that TRD in the chicken chromosome 16 might play an important role in chicken immunity and disease resistance and the MYH1F with significant TRD and allele-specific expression could play a key role in the fast muscle development. In addition, functional enrichment analyses revealed that many genes (e.g., TGFBR2, TGFBR3, NOTCH1, and NCOA1) with TRD were found in the significantly enriched biological process and InterPro terms in relation to embryonic lethality and germline selection. Our results suggested that TRD is considerably prevalent in the chicken genome and has functional implications.
RNA editing controls meiotic drive by a Neurospora Spore killer
24344N. A. Rhoades and T. M. Hammond, bioRxiv, 2020.12.30.424869. 2021-01-01 10:39:57.
Neurospora Sk-2 is a complex meiotic drive element that is transmitted to offspring through sexual reproduction in a biased manner. Sk-2’s biased transmission mechanism involves spore killing, and recent evidence has demonstrated that spore killing is triggered by a gene called rfk-1. However, a second gene, rsk, is also critically important for meiotic drive by spore killing because it allows offspring with an Sk-2 genotype to survive the toxic effects of rfk-1. Here, we present evidence demonstrating that rfk-1 encodes two protein variants: a 102 amino acid RFK-1A and a 130 amino acid RFK-1B, but only RFK-1B is toxic. We also show that expression of RFK-1B requires an early stop codon in rfk-1 mRNA to undergo adenosine-to-inosine (A-to-I) mRNA editing. Finally, we demonstrate that RFK-1B is toxic when expressed within vegetative tissue of Spore killer sensitive (SkS) strains, and that this vegetative toxicity can be overcome by co-expressing Sk-2’s version of RSK. Overall, our results demonstrate that Sk-2 uses RNA editing to control when its spore killer is produced, and that the primary killing and resistance functions of Sk-2 can be conferred upon an SkS strain by the transfer of only two genes.Competing Interest StatementThe authors have declared no competing interest.
Transgenic cotton and sterile insect releases synergize eradication of pink bollworm a century after it invaded the United States
15697B. E. Tabashnik, L. R. Liesner, P. C. Ellsworth, G. C. Unnithan, J. A. Fabrick, S. E. Naranjo, X. Li, T. J. Dennehy, L. Antilla, R. T. Staten and Y. Carrière, Proceedings of the National Academy of Sciences, 118:e2019115118. 2020-12-28 18:26:42.
The program included releases of billions of sterile pink bollworm moths from airplanes and planting of cotton engineered to produce insect-killing proteins from the bacterium Bacillus thuringiensis. Analysis of computer simulations and 21 y of field data from Arizona indicate these two tactics interacted synergistically to suppress the pest. By eradicating the pink bollworm, the program ended the damage it caused to cotton and the insecticide sprays used to control it, yielding economic, environmental, and social benefits.Invasive organisms pose a global threat and are exceptionally difficult to eradicate after they become abundant in their new habitats.
Genetic pest management and the background genetics of release strains
15695P. T. Leftwich, L. G. Spurgin, T. Harvey-Samuel, C. J. E. Thomas, L. C. Paladino, M. P. Edgington and L. Alphey, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190805. 2020-12-28 15:35:20.
We discuss issues around strain selection and the potential consequences of such introgression. We conclude that such introgression is probably harmless in almost all circumstances, and could, in theory, provide specific additional benefits to the release programme. We outline population monitoring approaches that could be used, going forward, to determine how background genetics may affect GPM. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.
Control of malaria-transmitting mosquitoes using gene drives
15693T. Nolan, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190803. 2020-12-28 15:31:23.
In this article, I will discuss the relative merits of this type of gene drive, as well as barriers to its technical development and to its deployment in the field as malaria control. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases'.
Genetic sexing strains for the population suppression of the mosquito vector Aedes aegypti
15691P. Koskinioti, A. A. Augustinos, D. O. Carvalho, M. Misbah-ul-Haq, G. Pillwax, L. D. d. l. Fuente, G. Salvador-Herranz, R. A. Herrero and K. Bourtzis, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190808. 2020-12-28 15:27:53.
Here, we report on the construction of two genetic sexing strains using red- and white-eye colour mutations as selectable markers. Quality control analysis showed that the Red-eye genetic sexing strains (GSS) is better and more genetically stable than the White-eye GSS. The introduction of an irradiation-induced inversion (Inv35) increases genetic stability and reduces the probability of female contamination of the male release batches. Bi-weekly releases of irradiated males of both the Red-eye GSS and the Red-eye GSS/Inv35 fully suppressed target laboratory cage populations within six and nine weeks, respectively
Wolbachia strain wAlbB maintains high density and dengue inhibition following introduction into a field population of Aedes aegypti
15689N. A. Ahmad, M.-V. Mancini, T. H. Ant, J. Martinez, G. M. R. Kamarul, W. A. Nazni, A. A. Hoffmann and S. P. Sinkins, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190809. 2020-12-28 15:06:28.
Here, wAlbB-carrying Ae. aegypti collected from the field 20 months after the cessation of releases showed no reduction in Wolbachia density or tissue distribution changes compared to a wAlbB laboratory colony. The wAlbB strain continued to induce complete unidirectional cytoplasmic incompatibility, showed perfect maternal transmission under laboratory conditions, and retained its capacity to inhibit dengue. Additionally, a field-collected wAlbB line was challenged with Malaysian dengue patient blood, and showed significant blocking of virus dissemination to the salivary glands.
Making gene drive biodegradable
15687J. Zapletal, N. Najmitabrizi, M. Erraguntla, M. A. Lawley, K. M. Myles and Z. N. Adelman, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190804. 2020-12-28 15:02:10.
Here, we consider the inclusion of self-elimination mechanisms into the design of homing-based gene drive transgenes. This approach not only caused the excision of the gene drive transgene, but also generates a transgene-free allele resistant to further action by the gene drive. Strikingly, our models suggest that this mechanism, acting at a modest rate (10%) as part of a single-component system, would be sufficient to cause the rapid reversion of even the most robust homing-based gene drive transgenes, without the need for further remediation.
Vector dynamics influence spatially imperfect genetic interventions against disease
16547M. K. Yuksel, C. H. Remien, B. Karki, J. J. Bull and S. M. Krone, Evolution, Medicine, and Public Health, 9:1-10. 2020-12-27 16:20:40.
In spatially structured populations, imperfect coverage of the vector will leave pockets in which the parasite may persist. Movement by humans may disrupt this local persistence and facilitate eradication when these pockets are small, spreading parasite reproduction outside unprotected areas and into areas that block its reproduction. Here, we consider the sensitivity of this process to biological details: do simple generalities emerge that may facilitate interventions?We develop formal mathematical models of this process similar to standard Ross–Macdonald models, but (i) specifying spatial structure of two patches, with vector transmission blocked in one patch but not in the other, (ii) allowing temporary human movement (travel instead of migration) and (iii) considering two different modes of mosquito biting.We find that there is no invariant effect of disrupting spatial structure with travel.
Application of the Relationship-Based Model to Engagement for Field Trials of Genetically Engineered Malaria Vectors
15898A. Kormos, G. C. Lanzaro, E. Bier, G. Dimopoulos, J. M. Marshall, J. Pinto, A. Aguiar dos Santos, A. Bacar, H. Sousa Pontes Sacramento Rompão and A. A. James, The American Journal of Tropical Medicine and Hygiene, 2020-12-21 14:17:29.
Although guidelines and recommendations for engagement for gene drives have recently been described, we argue here that communities and stakeholders should lead the planning, development, and implementation phases of engagement. The RBM provides a new approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs.
CRISPR/Cas9 knockout of female-biased genes AeAct-4 or myo-fem in Ae. aegypti results in a flightless phenotype in female, but not male mosquitoes
15617S. O’Leary and Z. N. Adelman, PLOS Neglected Tropical Diseases, 14:e0008971. 2020-12-18 16:05:35.
Author summary Ae. aegypti is the most important vector of arboviruses throughout the world, and new strategies are urgently needed to add to our existing arsenal of control methods to prevent or halt disease transmission. Importantly, only female Ae. aegypti mosquitoes transmit arboviruses due to their need for vertebrate blood to support egg production. Here, we identify several genes that are critical only for female mosquito flight; genetic ablation of each gene resulted in flightless females, but flying males. Importantly, the female flightless phenotype was completely penetrant (100%), and the use of sex-biased flight muscle proteins appeared to be conserved throughout mosquito evolution. These data could be used to support the development of novel genetic control approaches to reduce the number of biting females across a wide range of disease vector species.
Precise single base substitution in the shibire gene by CRISPR/Cas9-mediated homology directed repair in Bactrocera tryoni
16693A. Choo, E. Fung, I. Y. Chen, R. Saint, P. Crisp and S. W. Baxter, BMC Genetics, 21. 2020-12-18 15:58:10.
Here we introduce a known Drosophila melanogaster temperature sensitive embryonic lethal mutation into Bactrocera tryoni, a serious horticultural pest in Australia. A non-synonymous point mutation in the D. melanogaster gene shibire causes embryonic lethality at 29 degrees C and we successfully used CRISPR/Cas9 technology to recreate the orthologous shibire temperature sensitive-1 (shi(ts1)) mutation in B. tryoni. Genotypic analyses over three generations revealed that a high fitness cost was associated with the shi(ts1) mutant allele and shi(ts1) homozygotes were not viable at 21 degrees C, which is a more severe phenotype than that documented in D. melanogaster.ConclusionsWe have demonstrated the first successful use of CRISPR/Cas9 to introduce precise single base substitutions in an endogenous gene via homology-directed repair in an agricultural pest insect and this technology can be used to trial other conditional mutations for the ultimate aim of generating genetic sexing strains for SIT.
Gene Drive-Modified Organisms: Developing Practical Risk Assessment Guidance
15554Y. Devos, M. B. Bonsall, L. G. Firbank, J. Mumford, F. Nogué and E. A. Wimmer, Trends in Biotechnology, 2020-12-17 14:48:35.
Risk assessors, risk managers, developers, potential applicants, and other stakeholders at many levels discuss the need for new or further risk assessment guidance for deliberate environmental releases of gene drive-modified organisms. However, preparing useful and practical guidance entails challenges, to which we offer recommendations based on our experience drafting guidance.
A CRISPR endonuclease gene drive reveals two distinct mechanisms of inheritance bias
15480S. A. N. Verkuijl, E. González, J. X. D. Ang, M. Li, N. P. Kandul, M. Anderson, O. S. Akbari, M. Bonsall and L. Alphey, bioRxiv, 2020.12.15.421271. 2020-12-16 14:45:08.
In this study, we report the functioning of sds3, bgcn, and nup50 expressed Cas9 in an Aedes aegypti homing split drive system targeting the white gene. We report their inheritance biasing capability, propensity for maternal deposition, and zygotic/somatic expression. Additionally, by making use of the tight linkage of white to the sex-determining locus, we were able to elucidate mechanisms of inheritance bias. We find inheritance bias through homing in double heterozygous males, but find that a previous report of the same drive occurred through meiotic drive. We propose that other previously reported 'homing'design gene drives may in fact bias their inheritance through other mechanisms with important implications for gene drive design.Competing Interest StatementThe authors have declared no competing interest.
The Antiviral Small-Interfering RNA Pathway Induces Zika Virus Resistance in Transgenic Aedes aegypti
15482A. E. Williams, I. Sanchez-Vargas, W. R. Reid, J. Y. Lin, A. W. E. Franz and K. E. Olson, Viruses, 12:18. 2020-12-15 14:45:29.
We used CRISPR/Cas9 to re-target a previously characterized locus (Chr2:321382225) and engineered mosquitoes expressing an inverted repeat (IR) dsRNA against the NS3/4A region of the ZIKV genome. Small RNA analysis revealed that the IR effector triggered the mosquito's siRNA antiviral pathway in bloodfed females. Nearly complete (90%) inhibition of ZIKV replication was found in vivo in both midguts and carcasses at 7 or 14 days post-infection (dpi). Furthermore, significantly fewer transgenic mosquitoes contained ZIKV in their salivary glands (p = 0.001), which led to a reduction in the number of ZIKV-containing saliva samples as measured by transmission assay. Our work shows that Ae. aegypti innate immunity can be co-opted to engineer mosquitoes resistant to ZIKV.
Evading resistance to gene drives
15422R. Gomulkiewicz, M. L. Thies and J. J. Bull, bioRxiv, 2020.08.27.270611. 2020-12-12 15:44:15.
Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of moderate effect might cause only moderate population suppression, but multiple drives (perhaps delivered sequentially) would allow arbitrary levels of suppression. The most favorable case for evolution of resistance appears to be with suppression homing drives in which resistance is dominant and fully suppresses transmission distortion; partial suppression by resistance heterozygotes or recessive resistance are less prone to resistance evolution. Given that it is now possible to engineer CRISPR-based gene drives capable of circumventing allelic resistance, this design may allow for the engineering of suppression gene drives that are effectively resistance-proof.
Polyandry blocks gene drive in a wild house mouse population
15390A. Manser, B. Konig and A. K. Lindholm, Nature Communications, 11:8. 2020-12-11 14:12:22.
Here, we study the impact of polyandry on a well-known gene drive, called t haplotype, in an intensively monitored population of wild house mice. First, we show that house mice are highly polyandrous: 47% of 682 litters were sired by more than one male. Second, we find that drive-carrying males are particularly compromised in sperm competition, resulting in reduced reproductive success. As a result, drive frequency decreased during the 4.5 year observation period. Overall, we provide the first direct evidence that the spread of a gene drive is hampered by reproductive behaviour in a natural population.
Interdisciplinary development of a standardized introduction to gene drives for lay audiences
15381C. E. Schairer, C. Triplett, A. Buchman, O. S. Akbari and C. S. Bloss, BMC Medical Research Methodology, 20:15. 2020-12-10 15:09:37.
While there is wide consensus that the public should be consulted about emerging technology early in development, it is difficult to elicit public opinion about innovations unfamiliar to lay audiences. We sought public input on a program of research on genetic engineering to control mosquito vectors of disease that is led by scientists at the University of California and funded by the U.S. Defense Advanced Research Projects Agency (DARPA). In preparation for this effort, we developed a series of narrated slideshows to prompt responses to the development of gene drive mosquito control strategies among lay people. We describe the development and content of these slideshows and evaluate their ability to elicit discussions among focus group participants.
X-linked meiotic drive can boost population size and persistence
16876C. Mackintosh, A. Pomiankowski and M. F. Scott, Genetics, 217:11. 2020-12-10 14:26:46.
Here, we find general conditions for the spread and fixation of X-linked alleles. Our conditions show that the spread of X-linked alleles depends on sex-specific selection and transmission rather than the time spent in each sex. Applying this logic to meiotic drive, we show that polymorphism is heavily dependent on sperm competition induced both by female and male mating behavior and the degree of compensation to gamete loss in the ejaculate size of drive males. We extend these evolutionary models to investigate the demographic consequences of biased sex ratios. Our results suggest driving X-alleles that invade and reach polymorphism (or fix and do not bias segregation excessively) will boost population size and persistence time by increasing population productivity, demonstrating the potential for selfish genetic elements to move sex ratios closer to the population-level optimum. However, when the spread of drive causes strong sex-ratio bias, it can lead to populations with so few males that females remain unmated, cannot produce offspring, and go extinct. This outcome is exacerbated when the male mating rate is low. We suggest that researchers should consider the potential for ecologically beneficial side effects of selfish genetic elements, especially in light of proposals to use meiotic drive for biological control.
A patent review on strategies for biological control of mosquito vector
15377K. Parihar, M. Telang and A. Ovhal, World Journal of Microbiology and Biotechnology, 36:23. 2020-12-09 20:28:33.
This paper presents a comprehensive technology overview of patent documents disclosing biological agents for mosquito control. The patent analysis revealed that comparable number of patent documents were filed in two technology categories: non-recombinant agents and genetically modified (GM) agents. In the category of non-recombinant agents, toxic peptides from microbes and biological consortia seemed to be the earliest technology noted right from the year 1965 whereas the patent filings for suppression of mosquito population using genetic modification techniques have emerged from the year 2000 onwards. The United States of America is the leading patent filing jurisdiction followed by China and the Great Britain. Academic institutes have filed higher number of patent applications as compared to private companies. University of Florida was found to be the leading patent filing entity and its patents were focused on suppression of vector population using techniques such as release of insects with dominant lethal (RIDL) and RNA interference (RNAi).
Engineering a Culturable Serratia symbiotica Strain for Aphid Paratransgenesis
19389K. M. Elston, J. Perreau, G. P. Maeda, N. A. Moran and J. E. Barrick, Applied Environmental Microbiology, 87. 2020-12-06 17:18:42.
Aphids are global agricultural pests and important models for bacterial symbiosis. To date, none of the native symbionts of aphids have been genetically manipulated, which limits our understanding of how they interact with their hosts. Serratia symbiotica CWBI-2.3(T) is a culturable, gut-associated bacterium isolated from the black bean aphid. Closely related Serratia symbiotica strains are facultative aphid endosymbionts that are vertically transmitted from mother to offspring during embryogenesis. We demonstrate that CWBI-2.3(T) can be genetically engineered using a variety of techniques, plasmids, and gene expression parts. Then, we use fluorescent protein expression to track the dynamics with which CWBI-2.3(T) colonizes the guts of multiple aphid species, and we measure how this bacterium affects aphid fitness. Finally, we show that we can induce heterologous gene expression from engineered CWBI-2.3(T) in living aphids. These results inform the development of CWBI-2.3(T) for aphid paratransgenesis, which could be used to study aphid biology and enable future agricultural technologies.IMPORTANCE Insects have remarkably diverse and integral roles in global ecosystems. Many harbor symbiotic bacteria, but very few of these bacteria have been genetically engineered. Aphids are major agricultural pests and an important model system for the study of symbiosis. This work describes methods for engineering a culturable aphid symbiont, Serratia symbiotica CWBI-2.3(T) These approaches and genetic tools could be used in the future to implement new paradigms for the biological study and control of aphids.
Does RNAi-Based Technology Fit within EU Sustainability Goals?
C. N. T. Taning, B. Mezzetti, G. Kleter, G. Smagghe and E. Baraldi, Trends in Biotechnology, 2020-12-05 14:03:11.The Farm-to-Fork (F2F) strategyi, one of the pillars underneath the European Commission’s new Green Deal, aims to ensure a more sustainable and food-secure society. Its aims include a reduction in agrochemical inputs, such as pesticides, fertilizers, and antimicrobials, to achieve greater sustainability and health, and reduce loss of biodiversity while ensuring continued crop protection. It envisages various practices that promote lesser pesticide usage, such as integrated pest management (IPM), and the use of precision agriculture and artificial intelligence.
Targeting female flight for genetic control of mosquitoes
15310D. Navarro-Payá, I. Flis, M. A. E. Anderson, P. Hawes, M. Li, O. S. Akbari, S. Basu and L. Alphey, PLOS Neglected Tropical Diseases, 14:e0008876. 2020-12-03 20:11:01.
The yellow fever mosquito and the Southern house mosquito are important vectors of infectious diseases. Given their widespread presence across tropical and subtropical regions of the world and the increased risk of spread due to global warming there is a growing need for population control. Gene drives aim to spread a genetic element within target genes required for mosquito reproduction to disrupt their function and crash a population. Female-specific genes provide interesting candidates for population control since female mosquitoes determine the reproductive capacity of a population as well as being the actual vectors of disease. Here we describe a study on Actin-4 loss in both Aedes aegypti and Culex quinquefasciatus, where we observe female-specific disruption of flight ability and propose it as a candidate for genetic methods of population suppression.
Evaluating Gene Drive Approaches for Public Benefit
15296M. R. Santos, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:14:49.
Gene drive approaches—those which bias inheritance of a genetic element in a population of sexually reproducing organisms—have the potential to provide important public benefits. The spread of selected genetic elements in wild populations of organisms may help address certain challenges, such as transmission of vector-borne human and animal diseases and biodiversity loss due to invasive animals. Adapting various naturally occurring gene drive mechanisms to these aims is a long-standing research area, and recent advances in genetics have made engineering gene drive systems significantly more technically feasible. Gene drive approaches would act through changes in natural environments, thus robust methods to evaluate potential research and use are important.
Engineered Gene Drives and their Value in the Control of Vector-Borne Diseases, Weeds, Pests, and Invasive Species
15294K. Hefferon and R. Herring, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:10:55.
Genetic engineering has created potential for moving medical and agricultural research and application frontiers forward in unprecedented ways. Despite its accepted use as a powerful tool in medical research, genetic modification and genome editing technologies remain controversial in large-scale ecological intervention and open-field agriculture. Gene drive is a technology based on genome editing that enables a trait to be pushed through a given population at a greater than expected rate. While gene drives show enormous promise as a way to address a number of challenges, such as the reduction of populations of disease-spreading pests and invasive species, they also incite great social unease because of unknown risks. The following chapter describes the mechanics of gene drives and how they could be utilized to control vector-borne diseases, weeds, and crop pests and even protect populations of endangered species. Limitations and risks associated with gene drive technologies, such as containment strategies and potential resistance, are discussed. Finally, the social impacts of gene drives with respect to international governance and public acceptance are considered.
Engineered Gene Drives: Ecological, Environmental, and Societal Concerns
15292J. Kuzma, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:07:26.
This chapter overviews the types, purposes, and potential impacts of gene drive organisms (GDOs) and discusses challenges with foreseeing and assessing these impacts prior to their environmental release. It concludes with a few examples of risk analysis methods and governance systems that scholars have proposed to cope with the novelty of GDOs and uncertainties associated with their use. With GDOs poised for release in the near future, it is urgent that technologists, ecologists, social scientists, ethicists, stakeholders, and publics work together to grapple with the immense challenges associated with assessments of GDOs and the design of governance systems to ensure their responsible development and potential use.
Genetically Engineered Fish: Potential Impacts on Aquaculture, Biodiversity, and the Environment
15290R. A. Dunham and B. Su, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 17:03:48.
Studies on transgenic fish for the aquaculture industry have focused on improving growth rates, enhancing disease resistance, altering body composition, acting as biological factories for medical proteins, and even altering temperature tolerance and coloration. The future impact of transgenesis will likely be quite large. Growth hormone-transgenic salmon has been approved for human consumption and has been introduced to the market in Canada and soon to the USA. This is the first human consumption of approved transgenic meat. Transgene insertion has many pleiotropic effects. Several studies have projected the fitness of transgenic fish to be low, in general, compared to non-transgenic and wild fish; thus, their environmental risk is likely low and they would have minimal, if any, long-term impact on ecosystems or biodiversity. However, there have been no actual escapements; thus, only projections of risk are available based on small-scale experiments and the characteristics of transgenic fish compared to controls. An active area of research is repressible transgenic sterilization and sterilization using gene editing, both of which would allow application of transgenic fish with only short-term consequences for ecosystems in the worst-case scenario. Transgenic technology could also be potentially used to reduce or eliminate populations of nuisance species.
Invasive Species Control and Resolution of Wildlife Damage Conflicts: A Framework for Chemical and Genetically Based Management Methods
15286L. Clark, J. Eisemann, J. Godwin, K. E. Horak, K. Oh, J. O’Hare, A. Piaggio, K. Pepin and E. Ruell, GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 16:52:40.
Vertebrate wildlife damage management relates to developing and employing methods to mitigate against damage caused by wildlife in the areas of food production, property damage, and animal or human health and safety. Of the many management tools available
GMOs: Implications for Biodiversity Conservation and Ecological Processes
15283Chaurasia, Anurag , Hawksworth, David L., Pessoa de Miranda, Manoela., GMOs: Implications for Biodiversity Conservation and Ecological Processes, 2020-12-02 16:45:05.
This book covers a broad spectrum of topics related to GMOs and allied new gene-based technologies, biodiversity, and ecosystem processes, bringing together the contributions of researchers and regulators from around the world. The aim is to offer a clear view of the benefits and effects of genetically modified crops, insects, and other animals on the soil microbiome and ecological processes. Contributors examine issues related to the development of risk assessment procedures and regulations designed to maximize benefits while minimizing risks. Beyond the scientific challenges of GMOs, the book explores the broad and contentious terrain of ethical considerations. The contributors discuss such questions as the unintended, possibly unforeseen, consequences of releasing GMOs into ecosystems, and the likelihood that the full effects of GMOs could take years, even decades, of close monitoring to become evident. The importance of developing a precautionary approach is stressed.
Modelling the Wolbachia incompatible insect technique: strategies for effective mosquito population elimination
15281D. E. Pagendam, B. J. Trewin, N. Snoad, S. A. Ritchie, A. A. Hoffmann, K. M. Staunton, C. Paton and N. Beebe, BMC Biology, 18:13. 2020-12-02 16:29:23.
We introduce a simple Markov population process model for studying mosquito populations subjected to a Wolbachia-IIT programme which exhibit an unstable equilibrium threshold. The model is used to study, in silico, scenarios that are likely to yield a successful elimination result. Our results suggest that elimination is best achieved by releasing males at rates that adapt to the ever-decreasing wild population, thus reducing the risk of releasing Wolbachia-infected females while reducing costs.
Mosquito genomes are frequently invaded by transposable elements through horizontal transfer
15371E. S. de Melo and G. L. Wallau, PLOS Genetics, 16:e1008946. 2020-11-30 21:46:36.
We characterized the whole TE content of 24 mosquito genomes and investigated the TE inheritance mode uncovering hundreds of horizontal transfer events among these species and distantly related ones. We also identify a mosquito parasitic filarial worm, th
Strategic Approach, Advances, and Challenges in the Development and Application of the SIT for Area-Wide Control of Aedes albopictus Mosquitoes in Reunion Island
15267L. C. Gouagna, D. Damiens, C. F. Oliva, S. Boyer, G. Le Goff, C. Brengues, J.-S. Dehecq, J. Raude, F. Simard and D. Fontenille, Insects, 11:770. 2020-11-30 19:17:02.
Reply to: “Enhancement of Aedes aegypti susceptibility to dengue by Wolbachia is not supported”
15264C. Souto-Maior, J. G. King, L. M. Sartori, R. Maciel-de-Freitas and M. G. M. Gomes, Nature Communications, 11:6113. 2020-11-30 19:09:46.
Ant et al.4 claim that concerns with the data and broader analysis make our conclusions misleading. We herein respond to their comments by demonstrating the robustness of our results to different treatments of the data, and expand our arguments for replacing currently adopted methods by those introduced in our paper.
Enhancement of Aedes aegypti susceptibility to dengue by Wolbachia is not supported
15258T. H. Ant, M.-V. Mancini, J. Martinez and S. P. Sinkins, Nature Communications, 11:6111. 2020-11-30 18:48:33.
King et al.3 used DENV infection and transmission modelling to reinterpret experimental data from two previous studies4,5. The authors claimed that wMel Wolbachia increase the mean susceptibility of Ae. aegypti to DENV, contradicting various other studies6,7,8,9,10,11,12. Here, we raise concerns with the experimental approaches used to generate one of the primary datasets on which the modelling is based, and we discuss how these limitations could make some of the original conclusions misleading.
Toxin-Antidote Elements Across the Tree of Life
A. Burga, E. Ben-David and L. Kruglyak, Annual Review Genetics, 54:387-415. 2020-11-30 18:44:04.Toxin-antitoxin or toxin-antidote (TA) elements are genetic dyads that cheat the laws of inheritance to guarantee their transmission to the next generation. This seemingly simple genetic arrangement-a toxin linked to its antidote-is capable of quickly spreading and persisting in natural populations. TA elements were first discovered in bacterial plasmids in the 1980s and have recently been characterized in fungi, plants, and animals, where they underlie genetic incompatibilities and sterility in crosses between wild isolates. In this review, we provide a unified view of TA elements in both prokaryotic and eukaryotic organisms and highlight their similarities and differences at the evolutionary, genetic, and molecular levels.
Combined Effects of Mating Disruption, Insecticides, and the Sterile Insect Technique on Cydia pomonella in New Zealand
15958R. M. Horner, P. L. Lo, D. J. Rogers, J. T. S. Walker and D. M. Suckling, Insects, 11:23. 2020-11-27 18:11:55.
We aimed to supplement these tactics with the sterile insect technique (SIT) to further suppress the codling moth on orchards. SIT involves mass rearing and sterilizing codling moth and then releasing them onto orchards where they mate with wild insects resulting in no offspring. We released sterile insects onto seven orchards using unmanned aerial vehicles and ground releases. Six years of the program saw significant drops (90-99%) in wild moth populations. The SIT is an excellent tactic for reducing moth populations in export apple orchards.
Split drive killer-rescue provides a novel threshold-dependent gene drive
15254M. P. Edgington, T. Harvey-Samuel and L. Alphey, Scientific Reports, 10. 2020-11-25 18:32:01.
Population genetics mathematical models are developed here to demonstrate the threshold-dependent nature of the proposed system and its robustness to imperfect homing, incomplete penetrance of toxins and transgene fitness costs, each of which are of practical significance given that real-world components inevitably have such imperfections. We show that although end-joining repair mechanisms may cause the system to break down, under certain conditions, it should persist over time scales relevant for genetic control programs. The potential of such a system to provide localised population suppression via sex ratio distortion or female-specific lethality is also explored. Additionally, we investigate the effect on introduction thresholds of adding an extra CRISPR base element, showing that this may either increase or decrease dependent on parameter context
Transformation and slippage in co-production ambitions for global technology development: The case of gene drive
16634K. Ledingham and S. Hartley, Environmental Science & Policy, 116:78-85. 2020-11-24 17:41:43.
Co-production is an increasingly popular framework for knowledge generation, evaluation and decision making. Despite its potential to open up decisions and practices to the input of others, co-production regularly falls short of its transformative ambitions. Through documentary analysis, we investigate the meaning and dynamics of co-production as it stretches beyond the local into global research and technology spaces. We find that in the case of global gene drive, the meaning of co-production is extended in novel ways and underpinned by new possibilities for meaningful transformation. At the same time, we also identify a simultaneous resurfacing of reductive framings of collaboration. In the paper we present ‘slippage’ as a useful heuristic in helping to understand why co-production fails. We argue that if co-production in these new spaces is to achieve its transformative ambitions, there is a need to engage with new and entrenched knowledge hierarchies that contribute to this slippage.
Field Competitiveness of Aedes albopictus (Diptera: Culicidae) Irradiated Males in Pilot Sterile Insect Technique Trials in Northern Italy
16988R. Bellini, M. Carrieri, F. Balestrino, A. Puggioli, M. Malfacini and J. Bouyer, Journal of Medical Entomology, 58:807-813. 2020-11-20 14:50:15.
Vector-borne diseases account for 17% of infectious diseases, leading to more than one million deaths each year. Mosquitoes are responsible for 90% of the casualties and alternative control methods to insecticides are urgently needed, especially against Aedes vectors. Aedes albopictus is a particularly important species, causing major public health problems because it is a vector of several arboviruses and has a strong invasive behavior. Various genetic control methods have been proposed to be integrated into the management strategies of Aedes species, among which the sterile insect technique (SIT), which proved efficient against various insect pests and vectors. However, the ability of released irradiated sterile male mosquitoes to compete with their wild counterparts and induce sterility in wild females, which is critical to the success of this strategy, remained poorly defined. Here, we assessed the field competitiveness of Ae. albopictus irradiated male using data from eight release trials implemented in Northern Italy for 3 yr. Sterile males were capable of inducing a good level of sterility in the wild female population, however, with high variability in time and space. The field competitiveness of the released males was strongly negatively correlated with the ratio of sterile to wild males.This should be taken into consideration when designing future programs to suppress field populations of Aedes mosquitoes.
Sequence analysis in Bos taurus reveals pervasiveness of X–Y arms races in mammalian lineages
15219J. F. Hughes, H. Skaletsky, T. Pyntikova, N. Koutseva, T. Raudsepp, L. G. Brown, D. W. Bellott, T.-J. Cho, S. Dugan-Rocha, Z. Khan, C. Kremitzki, C. Fronick, T. A. Graves-Lindsay, L. Fulton, W. C. Warren, R. K. Wilson, E. Owens, J. E. Womack, W. J. Murphy, Genome Research, 2020-11-18 16:58:55.
Here, we provide evidence that suppression of X–Y crossing-over unleashed a second dynamic: selfish X–Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of Bos taurus (bull) and find it to be dominated by massive, lineage-specific amplification of testis-expressed gene families, making it the most gene-dense Y Chromosome sequenced to date. As in mice, an X-linked homolog of a bull Y-amplified gene has become testis-specific and amplified. This evolutionary convergence implies that lineage-specific X–Y coevolution through gene amplification, and the selfish forces underlying this phenomenon, were dominatingly powerful among diverse mammalian lineages. Together with Y gene decay, X–Y arms races molded mammalian sex chromosomes and influenced the course of mammalian evolution.
Engineering biological diversity: the international governance of synthetic biology, gene drives, and de-extinction for conservation
15251J. L. Reynolds, Current Opinion in Environmental Sustainability, 49:1-6. 2020-11-17 18:23:24.
In the face of insufficient progress in conserving and restoring biodiversity, the in situ use of advanced genetic modification, gene drives, and other biotechnologies for conservation purposes are being considered, researched, and developed. This paper introduces the methods, applications, environmental risks, and social challenges of ‘conservationist synthetic biology’; reviews existing governance, with an emphasis on international instruments, institutions, and processes; and offers observations of the politics of developing further governance. The most important multilateral environmental agreement is the Convention on Biological Diversity. Governance of such conservationist synthetic biology is vital but gaps remain. The further development of governance is a political process, and conservationist synthetic biology has a political landscape that is atypical for emerging technologies.
Assessment of a Novel Adult Mass-Rearing Cage for Aedes albopictus (Skuse) and Anopheles arabiensis (Patton).
15562H. Maïga, W. Mamai, N. S. Bimbilé Somda, T. Wallner, B. S. Poda, G. Salvador-Herranz, R. Argiles-Herrero, H. Yamada and J. Bouyer, Insects, 11:801. 2020-11-13 15:09:03.
Successful implementation of the sterile insect technique (SIT) against Aedes albopictus and Anopheles arabiensis relies on a continuous supply of sterile males. To meet this requirement, optimization of the mass-rearing techniques is needed. This study, therefore, aims to assess a new mass-rearing cage (MRC) in terms of egg production efficiency and egg hatch rate (quality). In addition, adult survival was evaluated based on a cage adult-index for Ae. albopictus. Moreover, the cage’s suitability for use in mass An. arabiensis egg production was compared to that of the FAO/IAEA Anopheles reference cage. In Ae. albopictus rearing, the new MRC produced 1,112,110 eggs per cage following six blood meals, with minimum loss of eggs in the egging water. Furthermore, the adult index gave a good proxy of daily mortality rates in Ae. albopictus. In An. arabiensis rearing, about 130,000 eggs per egg batch were collected both from the new and the reference MRC. These findings suggest that the new MRC prototype is efficient in terms of egg production and can be used for mass-rearing in SIT programs targeting Ae. albopictus as well as An. arabiensis. The adult index was also positively validated for the detection of unusual mortality rates in Ae. albopictus mass-rearing facilities. Overall, the new MRC has shown several advantages; however, further improvements are necessary to minimize escapes during the egg collection processes
Gene drives, species, and compassion for individuals in conservation biology
15072Y. Rohwer, Ethics, Policy and Environment, 2020-11-10 18:20:29.
In this paper I argue that these compassionate conservationists have a moral obligation to support the investigation and development of genetic modification technologies because of their potential to minimize suffering and eliminate killing in conservation. Furthermore, I will end the paper by suggesting that these genetic technologies can help avoid actions that could be damaging to one's moral character.
When Extinction is Warranted: Invasive Species, Suppression-Drives, and the Worst-Case Scenario
15050A. C. Thresher, Ethics, Policy and Environment, 2020-11-09 19:31:52.
The focus of this paper is on one such risk ? the danger of a suppression-drive escaping containment and wiping out the target species globally. Here, I argue that in most cases this risk is significant enough to warrant holding off on the technology. In some cases, however, we can bypass the precautionary principle by using a dominance approach that hinges on what I term the ?Worst-Case Clause?. This clause, in turn, provides us with a litmus test that can be fruitfully used to determine what species are viable targets for suppression-drives in the wild. Using this metric in concert with other considerations, I suggest that only three species are currently possible viable targets ? the European rabbit, ship rat, and Caribbean Tree Frog.
Modeling CRISPR gene drives for suppression of invasive rodents
15003S. E. Champer, N. Oakes, R. Sharma, P. García-Díaz, J. Champer and P. W. Messer, bioRxiv, 2020.11.05.369942. 2020-11-05 15:27:54.
Here, we develop a high-fidelity model of an island population of invasive rodents that includes three types of suppression gene drive systems. The individual-based model is spatially explicit and allows for overlapping generations and a fluctuating population size. Our model includes variables for drive fitness, efficiency, resistance allele formation rate, as well as a variety of ecological parameters.
A gene-drive rescue system for the modification of malaria mosquito populations
14901A. Adolfi, Nature Research Bioengineering Community, 2020-11-03 18:48:29.
Mosquito populations can now be reliably modified using 1) antimalarial molecules that block parasite development and 2) a CRISPR-based gene drive system that mediates their rapid spreading across the vector population.
A test for meiotic drive in hybrids between Australian and Timor zebra finches
15133U. Knief, W. Forstmeier, Y. Pei, J. Wolf and B. Kempenaers, Ecology and Evolution, 2020-11-03 16:16:43.
We did not find evidence for meiotic driver loci on specific chromosomes. However, we observed a weak overall transmission bias toward Timor alleles at centromeres in females (transmission probability of Australian alleles of 47%, nominal p = 6 ? 10?5). While this is in line with the centromere drive theory, it goes against the expectation that the subspecies with the larger effective population size (i.e., the Australian zebra finch) should have evolved the more potent meiotic drivers. We thus caution against interpreting our finding as definite evidence for centromeric drive. Yet, weak centromeric meiotic drivers may be more common than generally anticipated and we encourage further studies that are designed to detect also small effect meiotic drivers.

