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.
Fighting malaria with genetically modified mosquitoes
13609E. Nakkazi, BMJ, 370:m2172. 2020-08-04 12:53:14.
Could a bold project to genetically engineer mosquitoes curb the scourge of malaria in Africa? Finding out will require careful science—and public acceptance, writes Esther Nakkazi
Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi
13593A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, E. A. Bulger, A. Ramaiah, J. B. Bennett, G. Terradas, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James, bioRxiv, 2020.08.02.233056. 2020-08-02 12:59:26.
We developed the first recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion.
Extensive Recombination Suppression and Epistatic Selection Causes Chromosome-Wide Differentiation of a Selfish Sex Chromosome in Drosophila pseudoobscura
14296Z. L. Fuller, S. A. Koury, C. J. Leonard, R. E. Young, K. Ikegami, J. Westlake, S. Richards, S. W. Schaeffer and N. Phadnis, Genetics, 216:205. 2020-07-30 14:22:50.
Here, we conduct a multifaceted study of the multiply inverted Drosophila pseudoobscura SR chromosome to understand the evolutionary history, genetic architecture, and present-day dynamics that shape this enigmatic selfish chromosome.
A One-Sided Competition Mathematical Model for the Sterile Insect Technique
14287A. Ben Dhahbi, Y. Chargui, S. M. Boulaaras and S. Ben Khalifa, Complexity, 2020:12. 2020-07-30 13:59:01.
We study a simple mathematical model describing the dynamics of a wild-type pest insects population experiencing competition from sterile insects (one-sided competition).
Chemical controllable gene drive in Drosophila
13773D. Chae, J. Lee, N. Lee, K. Park, S. J. Moon and H. H. Kim, ACS Synthetic Biology, in press. 2020-07-30 12:48:10.
Here, we report a chemical-induced control of gene drive. We prepared a CRISPR-based gene drive system that can be removed by a site-specific recombinase, Rippase, the expression of which is induced by the chemical RU486 in fruit flies. Exposure of fruit flies to RU486 resulted in 7-12% removal of gene drive elements at each generation, leading to a significant reduction in gene drive-fly propagation.
Nix alone is sufficient to convert female Aedes aegypti into fertile males and myo-sex is needed for male flight
13780A. Aryan, M. A. E. Anderson, J. K. Biedler, Y. M. Qi, J. M. Overcash, A. N. Naumenko, M. V. Sharakhova, C. H. Mao, Z. N. Adelman and Z. J. Tu, Proceedings of the National Academy of Sciences of the United States of America, 117:17702-17709. 2020-07-28 13:17:04.
Here, we report the generation of multiple transgenic lines that express Nix under the control of its own promoter. Genetic and molecular analyses of these lines provided insights unattainable from previous transient experiments. We show that the Nix transgene alone, in the absence of the M-locus, was sufficient to convert females into males with all male-specific sexually dimorphic features and male-like gene expression.
The Biochemistry of Cytoplasmic Incompatibility Caused by Endosymbiotic Bacteria
18757H. Chen, M. Zhang and M. Hochstrasser, Genes, 11. 2020-07-25 14:17:05.
Many species of arthropods carry maternally inherited bacterial endosymbionts that can influence host sexual reproduction to benefit the bacterium. The most well-known of such reproductive parasites is Wolbachia pipientis. Wolbachia are obligate intracellular α-proteobacteria found in nearly half of all arthropod species. This success has been attributed in part to their ability to manipulate host reproduction to favor infected females. Cytoplasmic incompatibility (CI), a phenomenon wherein Wolbachia infection renders males sterile when they mate with uninfected females, but not infected females (the rescue mating), appears to be the most common. CI provides a reproductive advantage to infected females in the presence of a threshold level of infected males. The molecular mechanisms of CI and other reproductive manipulations, such as male killing, parthenogenesis, and feminization, have remained mysterious for many decades. It had been proposed by Werren more than two decades ago that CI is caused by a Wolbachia-mediated sperm modification and that rescue is achieved by a Wolbachia-encoded rescue factor in the infected egg. In the past few years, new research has highlighted a set of syntenic Wolbachia gene pairs encoding CI-inducing factors (Cifs) as the key players for the induction of CI and its rescue. Within each Cif pair, the protein encoded by the upstream gene is denoted A and the downstream gene B. To date, two types of Cifs have been characterized based on the enzymatic activity identified in the B protein of each protein pair; one type encodes a deubiquitylase (thus named CI-inducing deubiquitylase or cid), and a second type encodes a nuclease (named CI-inducing nuclease or cin). The CidA and CinA proteins bind tightly and specifically to their respective CidB and CinB partners. In transgenic Drosophila melanogaster, the expression of either the Cid or Cin protein pair in the male germline induces CI and the expression of the cognate A protein in females is sufficient for rescue. With the identity of the Wolbachia CI induction and rescue factors now known, research in the field has turned to directed studies on the molecular mechanisms of CI, which we review here.
The potential for a CRISPR gene drive to eradicate or suppress globally invasive social wasps
13486P. J. Lester, M. Bulgarella, J. W. Baty, P. K. Dearden, J. Guhlin and J. M. Kean, Scientific Reports, 10:12398. 2020-07-24 17:41:41.
P. J. Lester, M. Bulgarella, J. W. Baty, P. K. Dearden, J. Guhlin and J. M. Kean (2020). Scientific Reports. doi: 10.1038/s41598-020-69259-6 Gene drives have potential for widespread and cost-efficient pest control, but are highly controversial. We examined a potential gene drive targeting spermatogenesis to control the invasive common wasp (Vespula vulgaris) in New Zealand.
Providing a policy framework for responsible gene drive research: an analysis of the existing governance landscape and priority areas for further research
13231D. Thizy, I. Coche and J. de Vries, Wellcome Open Research, 2020-07-20 12:19:36.
D. Thizy, I. Coche and J. de Vries (2020). Wellcome Open Research. doi: 10.12688/wellcomeopenres.16023.1 In this manuscript, we review the existing regulatory landscape around gene drive research and map areas of convergence and divergence, as well as gaps in relation to guidelines for community engagement in gene drive research.
Socrates Untenured: Ethics, Experts, and the Public in the Synthetic Age
13182C. Preston, ISSUES in Science and Technology, 2020-07-14 17:44:20.
C. Preston (2020). Three tools have transformed biotechnology over the past decade and a half. Gene reading has made it possible to quickly sequence the genome of any living creature. Gene synthesis has made it possible to construct DNA sequences in the lab from constituent chemicals. Gene editing has made it possible to place those sections into an existing DNA sequence at any point a technician chooses.
Genome Editing 2020: Ethics and Human Rights in Germline Editing in Humans and Gene Drives in Mosquitoes
13198G. J. Annas, American Journal of Law and Medicine, 46:143-165. 2020-07-12 18:17:19.
G. J. Annas (2020). American Journal of Law and Medicine. doi: 10.1177/0098858820933492. I begin with a discussion of so far disastrously unsuccessful attempts to regulate germline editing in humans, including a summary of the first application of germline genome editing in humans and its aftermath. I then turn to a discussion of setting ethical standards for a genomic technology that has not yet been deployed in nature—gene drives. Finally, I end by suggesting that human rights can and should be directly applicable to defining the ethics of genomic research.
On Nonlinear Pest/Vector Control via the Sterile Insect Technique: Impact of Residual Fertility
14291M. S. Aronna and Y. Dumont, Bulletin of Mathematical Biology, 82:29. 2020-07-09 14:09:49.
We consider a minimalist model for the Sterile Insect Technique (SIT), assuming that residual fertility can occur in the sterile male population.
2-Locus Cleave and Rescue; selfish elements harness a recombination rate-dependent generational clock for self limiting gene drive
13150G. Oberhofer, T. Ivy and B. A. Hay, bioRxiv, 2020-07-09 14:03:42.
Self-limiting gene drive allows control over the spread and fate of linked traits. Cleave and Rescue (ClvR) elements create self-sustaining drive and comprise a DNA sequence-modifying enzyme (Cas9-gRNAs, Cleaver) that disrupts an essential gene, and a tightly linked, uncleavable version of the essential gene (Rescue). ClvR spreads by creating conditions in which those without it die because they lack essential gene function. We show that when ClvR is implemented in a 2-locus format, with key elements – Rescue (and Cargo), and Cas9 and/or gRNAs – located at different genomic positions, spread of the Rescue is self-limiting. Drive strength and duration are determined by a recombination rate-dependent generational clock, providing an important point of control for different ecological and regulatory contexts. We implement 2-locus ClvR in Drosophila. Rescue spreads to high frequency in a Cas9-dependent manner, while the frequency of Cas9 decreases, demonstrating transient drive and loss of future drive potential.
Maternal effect killing by a supergene controlling ant social organization
12741A. Avril, J. Purcell, S. Béniguel and M. Chapuisat, Proceedings of the National Academy of Sciences, 2020-07-07 13:29:50.
Supergenes are clusters of linked loci producing complex alternative phenotypes. In a series of experiments, we demonstrate that a supergene controlling ant social organization distorts Mendel’s laws to enhance its transmission to adult offspring. One supergene haplotype is specific to multiple-queen colonies. This haplotype kills half of the offspring from heterozygous mothers—all eggs that do not inherit the haplotype fail to hatch. Hence, the haplotype associated with multiple-queen colonies is a selfish genetic element favoring its transmission to the detriment of the alternate haplotype associated with single-queen colonies. Selfish gene drive by a large group of linked genes impacts the social organization of ant colonies, which illustrates the intricate multilevel effects of supergenes.Supergenes underlie striking polymorphisms in nature, yet the evolutionary mechanisms by which they arise and persist remain enigmatic. These clusters of linked loci can spread in populations because they captured coadapted alleles or by selfishly distorting the laws of Mendelian inheritance. Here, we show that the supergene haplotype associated with multiple-queen colonies in Alpine silver ants is a maternal effect killer. All eggs from heterozygous queens failed to hatch when they did not inherit this haplotype. Hence, the haplotype specific to multiple-queen colonies is a selfish genetic element that enhances its own transmission by causing developmental arrest of progeny that do not carry it. At the population level, such transmission ratio distortion favors the spread of multiple-queen colonies, to the detriment of the alternative haplotype associated with single-queen colonies. Hence, selfish gene drive by one haplotype will impact the evolutionary dynamics of alternative forms of colony social organization. This killer hidden in a social supergene shows that large nonrecombining genomic regions are prone to cause multifarious effects across levels of biological organization.
Artificial Selection Finds New Hypotheses for the Mechanism of Wolbachia-Mediated Dengue Blocking in Mosquitoes
13600S. A. Ford, I. Albert, S. L. Allen, S. F. Chenoweth, M. Jones, C. Koh, A. Sebastian, L. T. Sigle and E. A. McGraw, Frontiers in Microbiology, 11:1456. 2020-07-07 13:18:12.
We recently used experimental evolution to reveal that Wolbachia-mediated dengue blocking could be selected upon in the A. aegypti host and showed evidence that strong levels of blocking could be maintained by natural selection. In this study, we investigate the genetic variation associated with blocking and use these analyses to generate testable hypotheses surrounding the mechanism of Wolbachia-mediated dengue blocking.
Small-Molecule Control of Super-Mendelian Inheritance in Gene Drives
12711V. López Del Amo, B. S. Leger, K. J. Cox, S. Gill, A. L. Bishop, G. D. Scanlon, J. A. Walker, V. M. Gantz and A. Choudhary, Cell Reports, 31:107841. 2020-06-30 20:53:02.
Summary Synthetic CRISPR-based gene-drive systems have tremendous potential in public health and agriculture, such as for fighting vector-borne diseases or suppressing crop pest populations. These elements can rapidly spread in a population by breaching the inheritance limit of 50% dictated by Mendel’s law of gene segregation, making them a promising tool for population engineering. However, current technologies lack control over their propagation capacity, and there are important concerns about potential unchecked spreading. Here, we describe a gene-drive system in Drosophila that generates an analog inheritance output that can be tightly and conditionally controlled to between 50% and 100%. This technology uses a modified SpCas9 that responds to a synthetic, orally available small molecule, fine-tuning the inheritance probability. This system opens a new avenue to feasibility studies for spatial and temporal control of gene drives using small molecules.
Invasion and maintenance of spore killers in populations of ascomycete fungi
15129I. Martinossi-Allibert, C. Veller, S. L. Ament-Velásquez, A. A. Vogan, C. Rueffler and H. Johannesson, bioRxiv, 2020.04.06.026989. 2020-06-30 16:08:48.
We show how ploidy level, rate of selfing, and efficiency of spore killing affect the invasion probability of a driving allele and the conditions for its stable coexistence with the non-driving allele. Our model can be adapted to different fungal life-cycles, and is applied here to two well-studied genera of filamentous ascomycetes known to harbor spore killing elements, Podospora and Neurospora. We discuss our results in the light of recent empirical findings for these two systems.Competing Interest StatementThe authors have declared no competing interest.
Role of gene drives in malaria elimination strategy: modeling impact and cost-effectiveness in the Democratic Republic of the Congo
12729N. Metchanun, C. Borgemeister, J. von Braun, M. Nikolov, P. Selvaraj and J. Gerardin, medRxiv, 2020-06-29 13:15:39.
The tremendous burden of malaria has led to renewed efforts on malaria elimination and the development of novel tools for application where existing tools fall short. Gene drive mosquitoes, where transgenes and their associated phenotypes are efficiently propagated to future generations, are under development to suppress vector populations or render vectors incapable of malaria transmission. However, the role of gene drives in an integrated elimination strategy is underexplored. Using a spatially explicit agent-based model of malaria transmission in the Democratic Republic of the Congo, we describe the impact of integrating a population suppression driving-Y gene drive into malaria elimination strategies. We find that as long as the driving-Y construct is extremely effective, releases of gene drive mosquitoes can eliminate malaria, and we identify a cost ceiling for gene drive to be cost-effective relative to existing tools. Vector control via gene drive is worth considering as a supplemental intervention when the construct parameters and costs are suitable.
Can natural gene drives be part of future fungal pathogen control strategies in plants?
12564D. M. Gardiner, A. Rusu, L. Barrett, G. C. Hunter and K. Kazan, New Phtologist, 2020-06-28 19:10:13.
Globally, fungal pathogens cause enormous crop losses and current control practices are not always effective, economical or environmentally sustainable. Tools enabling genetic management of wild pathogen populations could potentially solve many problems associated with plant diseases. A natural gene drive from a heterologous species can be used in the globally important cereal pathogen, Fusarium graminearum, to remove pathogenic traits from contained populations of the fungus. The gene drive element became fixed in a freely crossing populations in only three generations. Repeat induced point mutation (RIP), a natural genome defence mechanism in fungi that causes C to T mutations during meiosis in highly similar sequences, may be useful to recall the gene drive following release, should a failsafe mechanism be required. We propose that gene drive technology is a potential tool to control plant pathogens once its efficacy is demonstrated under natural settings.
Translating gene drive science to promote linguistic diversity in community and stakeholder engagement
12560C. Cheung, S. Gamez, R. Carballar-Lejarazú, V. Ferman, V. N. Vásquez, G. Terradas, J. Ishikawa, C. E. Schairer, E. Bier, J. M. Marshall, A. A. James, O. S. Akbari and C. S. Bloss, Global Public Health, 2020-06-26 18:55:10.
Information about genetic engineering (GE) for vector control in the United States is disseminated primarily in English, though non-English speakers are equally, and in some geographic regions even more affected by such technologies. Non-English-speaking publics should have equal access to such information, which is especially critical when the technology in question may impact whole communities. We convened an interdisciplinary workgroup to translate previously developed narrated slideshows on gene drive mosquitoes from English into Spanish, reviewing each iteration for scientific accuracy and accessibility to laypeople. Using the finalised stimuli, we conducted five online, chat-based focus groups with Spanish-speaking adults from California. Overall, participants expressed interest in the topic and were able to summarise the information presented in their own words. Importantly, participants asked for clarification and expressed scepticism about the information presented, indicating critical engagement with the material. Through collaboration with Spanish-speaking scientists engaged in the development of GE methods of vector control, we translated highly technical scientific information into Spanish that successfully engaged Spanish-speaking participants in conversations about this topic. In this manuscript, we document the feasibility of consulting Spanish-speaking publics about a complex emerging technology by drawing on the linguistic diversity of the scientific teams developing the technology.
Development of zygotic and germline gene drives in mice
12531C. Pfitzner, J. N. Hughes, M. A. White, M. Scherer, S. G. Piltz and P. Q. Thomas, bioRxiv, 2020-06-21 15:15:40.
Here we investigated the efficiency of CRISPR/Cas9-based gene drives in Mus musculus by constructing "split drive" systems with Cas9 under the control of zygotic (CAG) or germline (Vasa) promoters.
Analysis of a Strong Suppressor of Segregation Distorter inDrosophila melanogaster
14264R. G. Temin, Genetics, 215:1085-1105. 2020-06-19 14:59:33.
These studies highlight the polygenic nature of distortion and its dependence on a constellation of positive and negative modifiers, provide insight into the stability of Mendelian transmission in natural populations even when a drive system arises, and pave the way for molecular characterization ofSu(SD)whose identity should reveal new information about the mechanism of distortion.
Genetic breakdown of a Tet-off conditional lethality system for insect population control
13152Y. Zhao, M. F. Schetelig and A. M. Handler, Nature Communications, 11:3095. 2020-06-18 14:12:25.
Genetically modified conditional lethal strains have been created to improve the control of insect pest populations damaging to human health and agriculture. However, understanding the potential for the genetic breakdown of lethality systems by rare spontaneous mutations, or selection for inherent suppressors, is critical since field release studies are in progress. This knowledge gap was addressed in a Drosophila tetracycline-suppressible embryonic lethality system by analyzing the frequency and structure of primary-site spontaneous mutations and second-site suppressors resulting in heritable survivors from 1.2 million zygotes. Here we report that F1 survivors due to primary-site deletions and indels occur at a 5.8 × 10−6 frequency, while survival due to second-site maternal-effect suppressors occur at a ~10−5 frequency. Survivors due to inherent lethal effector suppressors could result in a resistant field population, and we suggest that this risk may be mitigated by the use of dual redundant, albeit functionally unrelated, lethality systems.
Detecting the population dynamics of an autosomal sex ratio distorter transgene in malaria vector mosquitoes
13607P. Pollegioni, A. R. North, T. Persampieri, A. Bucci, R. L. Minuz, D. A. Groneberg, T. Nolan, P. A. Papathanos, A. Crisanti and R. Muller, Journal of Applied Ecology, 11. 2020-06-18 12:44:16.
A sex-distorting autosomal transgene has been developed recently in G3 mosquitoes, a laboratory strain of the malaria vectorAnopheles gambiaes.l. Following the World Health Organization guidance framework for the testing of GM mosquitoes, we assessed the dynamics of this transgene in large cages using a joint experimental modelling approach. We performed a 4-month experiment in large, indoor cages to study the population genetics of the transgene.
Field performance of sterile male mosquitoes released from an uncrewed aerial vehicle
12708J. Bouyer, N. J. Culbert, A. H. Dicko, M. G. Pacheco, J. Virginio, M. C. Pedrosa, L. Garziera, A. T. M. Pinto, A. Klaptocz, J. Germann, T. Wallner, G. Salvador-Herranz, R. A. Herrero, H. Yamada, F. Balestrino and M. J. B. Vreysen, Science Robotics, 5:10. 2020-06-15 20:48:48.
Genetic control methods of mosquito vectors of malaria, dengue, yellow fever, and Zika are becoming increasingly popular due to the limitations of other techniques such as the use of insecticides. The sterile insect technique is an effective genetic control method to manage insect populations. However, it is crucial to release sterile mosquitoes by air to ensure homogeneous coverage, especially in large areas. Here, we report a fully automated adult mosquito release system operated from an uncrewed aerial vehicle or drone. Our system, developed and tested in Brazil, enabled a homogeneous dispersal of sterile male Aedes aegypti while maintaining their quality, leading to a homogeneous sterile-to-wild male ratio due to their aggregation in the same sites. Our results indicate that the released sterile males were able to compete with the wild males in mating with the wild females; thus, the sterile males were able to induce sterility in the native female population. The use of drones to implement the sterile insect technique will lead to improvements in areal coverage and savings in operational costs due to the requirement of fewer release sites and field staff.
The need for new vector control approaches targeting outdoor biting anopheline malaria vector communities
12808S. Sougoufara, E. C. Ottih and F. Tripet, Parasites & Vectors, 13:15. 2020-06-10 19:48:24.
Since the implementation of Roll Back Malaria, the widespread use of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) is thought to have played a major part in the decrease in mortality and morbidity achieved in malaria-endemic regions. In the past decade, resistance to major classes of insecticides recommended for public health has spread across many malaria vector populations. Increasingly, malaria vectors are also showing changes in vector behaviour in response to current indoor chemical vector control interventions. Changes in the time of biting and proportion of indoor biting of major vectors, as well as changes in the species composition of mosquito communities threaten the progress made to control malaria transmission. Outdoor biting mosquito populations contribute to malaria transmission in many parts of sub-Saharan Africa and pose new challenges as they cannot be reliably monitored or controlled using conventional tools. Here, we review existing and novel approaches that may be used to target outdoor communities of malaria vectors. We conclude that scalable tools designed specifically for the control and monitoring of outdoor biting and resting malaria vectors with increasingly complex and dynamic responses to intensifying malaria control interventions are urgently needed. These are crucial for integrated vector management programmes designed to challenge current and future vector populations.
Gene Drive: Can this be the Future of Agricultural Pest Management?
13156P. Mondal, U. Mohapatra and M. Ganguly, International Journal of Current Microbiology and Applied Sciences, 9. 2020-06-10 14:25:16.
A world free of hunger may be possible when the agricultural production exceeds the global demand for the food. In the era of increasing population, the need for increased food production can be attainable by managing the destructive pests of the agricultural and horticultural crops. The detrimental effects of the pesticides and the attitudes of society towards transgenic crops indicate the researchers to catch out Gene Drive as the substitute method for former methods of crop pest management. In this context, the present narration describes how the self-sustaining CRISPR-based gene drive technology will be the leading technique in the near future for agriculture pest management.
Conservation implications of disease control
12540J. C. Buck, S. B. Weinstein, G. Titcomb and H. S. Young, Frontiers in Ecology and the Environment, 6. 2020-06-08 15:44:22.
Infectious diseases have indelibly altered human history and, in doing so, have shaped the ecology and conservation of the natural world. Attempts to control diseases often result in adverse environmental impacts, including habitat degradation and unintended outcomes such as effects on non-target species. However, in instances where the most effective strategy is to physically avoid specific species or habitats, disease can also provide critical de facto conservation benefits to organisms and ecosystems. Increasingly, new genome-editing technologies offer the potential to eradicate long-term health scourges, which disproportionately affect people in developing countries. It will be critical to incorporate an understanding of the ecological consequences of disease control - including those mediated by changes in human behavior - into management strategies, and to do so without propagating environmental injustice. In this way, scientists, resource managers, and health practitioners can help to ensure that gains for human health do not result in losses for the natural world.
Meiotic drive
12538A. N. Srinivasa and S. E. Zanders, Current Biology, 30:R627-R629. 2020-06-08 15:35:32.
What is meiotic drive? Diploid organisms, like you, have two copies of each autosomal chromosome, one from each parent. Sometimes organisms are heterozygous at a given region, meaning they carry different copies (or alleles) of the DNA sequence on the two homologous chromosomes. Generally, the alternative alleles at a given site have an equal chance of being transmitted into the next generation by way of gametes (like sperm or eggs). A man with XY sex chromosomes, for example, will generate an equal number of X-bearing and Y-bearing sperm. This will lead him to father male and female offspring with equal probability. This Mendelian allele transmission constitutes one of the foundational laws of genetics. Meiotic drivers are alleles that break this law and force their transmission into more than half or sometimes even all of the progeny.
Motivations and expectations driving community participation in entomological research projects: Target Malaria as a case study in Bana, Western Burkina Faso
12435N. Barry, P. Toé, L. Pare Toe, J. Lezaun, M. Drabo, R. K. Dabiré and A. Diabate, Malaria Journal, 19:199. 2020-06-05 20:15:19.
Most field entomology research projects require active participation by local community members. Since 2012, Target Malaria, a not-for-profit research consortium, has been working with residents in the village of Bana, in Western Burkina Faso, in various studies involving mosquito collections, releases and recaptures. The long-term goal of this work is to develop innovative solutions to combat malaria in Africa with the help of mosquito modification technologies. Since the start of the project, Bana residents have played an important role in research activities, yet the motivations and expectations that drive their participation remain under-investigated. This study examines the factors that motivate some members of the local community to contribute to the implementation of Target Malaria’s activities, and, more broadly, explores the reasons that animate citizen participation in entomological research work in malaria-endemic regions.
Gene drives: benefits, risks, and possible applications
12414A. Deplazes-Zemp, U. Grossniklaus, F. Lefort, P. Müller, J. Romeis, A. Rüegsegger, N. Schoenenberger and E. Spehn, Swiss Academies Factsheets, 15. 2020-06-05 19:48:13.
Gene drives are genetic elements that skew the pattern of inheritance of a given characteristic in sexually reproducing organisms. They can be used to spread a characteristic that can alter or even reduce the numbers of individuals in wild populations of a certain species. As they spread by being inherited from one generation to the next, they could persist in populations long-term. The spreading property of gene drives could be a source of great potential in areas as diverse as the control of disease vectors, invasive species, agricultural pests and predators of endangered species. However, the same property may make containment challenging and therefore may also pose novel environmental risks. The evaluation, distribution of risks and benefits and the fact that gene drives may be seen as a particularly profound interference with nature raises further novel ethical considerations.
CRISPR/Cas9 gene drive technology to control transmission of vector-borne parasitic infections
12386M. Nateghi Rostami, Parasite Immunology, preprint:e12762. 2020-06-04 18:10:02.
Gene drive is the process of copying of an endonuclease-containing cassette that leads to increased frequency of inheritance of the desired traits in a targeted population. CRISPR/Cas9 technology is advancing genetic manipulation of insects in the field of gene drive experiments. The CRISPR/Cas9 drive could be engineered for genetic manipulation of parasites and/or vectors for disease control. A number of promising CRISPR/Cas9-based gene drive strategies that interfere with parasite development or impairs the reproductive capability of the insect vector, have been proposed in the laboratory for blocking transmission of malaria and leishmaniasis. Still several technical and ethical challenges remain to be addressed, none appear insuperable in this field.
Can CRISPR gene drive work in pest and beneficial haplodiploid species?
12389J. Li, O. Aidlin Harari, A.-L. Doss, L. L. Walling, P. W. Atkinson, S. Morin and B. E. Tabashnik, Evolutionary Applications, 2020-06-03 18:14:33.
Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known about CRISPR gene drive in haplodiploids, despite their immense global impacts as pollinators, pests, natural enemies of pests, and invasive species in native habitats. Here we analyze mathematical models demonstrating that, in principle, CRISPR homing gene drive can work in haplodiploids, as well as at sex-linked loci in diploids. However, relative to diploids, conditions favoring the spread of alleles deleterious to haplodiploid pests by CRISPR gene drive are narrower, the spread is slower, and resistance to the drive evolves faster. By contrast, the spread of alleles that impose little fitness cost or boost fitness was not greatly hindered in haplodiploids relative to diploids. Therefore, altering traits to minimize damage caused by harmful haplodiploids, such as interfering with transmission of plant pathogens, may be more likely to succeed than control efforts based on introducing traits that reduce pest fitness. Enhancing fitness of beneficial haplodiploids with CRISPR gene drive is also promising.
Islands as Laboratories: Indigenous Knowledge and Gene Drives in the Pacific
12391R. I. Taitingfong, Human Biology, 91:179-188. 2020-06-01 18:19:55.
This article argues that the genetic engineering technology known as gene drive must be evaluated in the context of the historic and ongoing impacts of settler colonialism and military experimentation on indigenous lands and peoples. After defining gene drive and previewing some of the key ethical issues related to its use, the author compares the language used to justify Cold War–era nuclear testing in the Pacific with contemporary scholarship framing islands as ideal test sites for gene drive–modified organisms. In both cases, perceptions of islands as remote and isolated are mobilized to warrant their treatment as sites of experimentation for emerging technologies. Though gene drive may offer valuable interventions into issues affecting island communities (e.g., vector-borne disease and invasive species management), proposals to conduct the first open trials of gene drive on islands are complicit in a long history of injustice that has treated islands (and their residents) as dispensable to the risks and unintended consequences associated with experimentation. This article contends that ethical gene drive research cannot be achieved without the inclusion of indigenous peoples as key stakeholders and provides three recommendations to guide community engagement involving indigenous communities: centering indigenous self-determination, replacing the deficit model of engagement with a truly participatory model, and integrating indigenous knowledge and values in the research and decision-making processes related to gene drive.
A Protamine Knockdown Mimics the Function of Sd in Drosophila melanogaster
12536L. F. Gingell and J. R. McLean, G3-Genes Genomes Genetics, 10:2111-2115. 2020-06-01 15:29:52.
Segregation Distorter (SD) is an autosomal meiotic drive system found worldwide in natural populations of Drosophila melanogaster. This gene complex induces the preferential and nearly exclusive transmission of the SD chromosome in SD/SD+ males. This selfish propagation occurs through the interplay of the Sd locus, its enhancers and the Rsp(s) locus during spermatid development. The key distorter locus, Sd, encodes a truncated but enzymatically active RanGAP (RanGTPase-activating protein), a key nuclear transport factor in the Ran signaling pathway. When encoded by Sd, RanGAP is mislocalized to the nucleus interior, which then traps Ran inside the nucleus and disrupts nuclear import. As a result of this aberrant nuclear transport, a process known as the histone-to-protamine transition that is required for proper spermatid condensation fails to occur in SD/SD+ males. In this process, sperm-specific protamine proteins enter the spermatid nucleus and replace the formerly chromatin-complexed histones. Previously, we have shown that mutations affecting nuclear import and export can enhance distortion in an SD background, thus verifying that a defect in nuclear transport is responsible for the unequal transmission of chromosomes. Herein, we show that specifically reducing protamines induces distortion in an SD background, verifying that protamines are transported via the RanGAP/GEF pathway and indicating that E(SD) plays a significant and unique role in the process of distortion
Engineered Gene Drives for Pest Management
25478G. Miglani, Biotechnology for Plant Disease Diagnosis and Management, 2020-06-01 09:06:32.
Genes in sexually reproducing organisms normally have, on average, a 50% chance of being inherited, but some genes have a higher chance of being inherited. These genes can increase in relative frequency in a population even if they reduce the odds that each organism will reproduce. Aided by technological advances, scientists are investigating how populations might be altered by adding, disrupting, or editing genes or suppressed by propagating traits that reduce reproductive capacity. Due to the discovery of gene-drive systems in insects and with the development of gene-drive technology using engineered site-specific nucleases, the last couple of years have seen a profound rise in excitement about the many possible uses of gene drive systems (GDSs). GDSs are capable of altering the traits of wild populations and associated ecosystems. A gene drive biases the transmission of a particular allele of a gene such that it is inherited at a greater frequency than by random assortment. A consequence of gene drives is an increased frequency of specific genetic elements or alleles and their accelerated spread throughout populations over successive generations. Here we will first describe the discovery, characteristics, types and mechanisms of GDSs. Next we will deal with development of gene-drive technology and its applications with special reference to their use in pest management and progresses that have so far been made to apply gene-drive systems in this area of research followed by limitations, safety and regulatory aspects of this technology. Finally, we will take up some key questions and future prospects of this important but still under-refinement technology.
Bioengineering horizon scan 2020
12449L. Kemp, L. Adam, C. R. Boehm, R. Breitling, R. Casagrande, M. Dando, A. Djikeng, N. G. Evans, R. Hammond, K. Hills, L. A. Holt, T. Kuiken, A. Markotić, P. Millett, J. A. Napier, C. Nelson, S. S. ÓhÉigeartaigh, A. Osbourn, M. J. Palmer, N. J. Patron, E. P, eLife, 9:e54489. 2020-05-29 20:28:54.
Horizon scanning is intended to identify the opportunities and threats associated with technological, regulatory and social change. In 2017 some of the present authors conducted a horizon scan for bioengineering (Wintle et al., 2017). Here we report the results of a new horizon scan that is based on inputs from a larger and more international group of 38 participants. The final list of 20 issues includes topics spanning from the political (the regulation of genomic data, increased philanthropic funding and malicious uses of neurochemicals) to the environmental (crops for changing climates and agricultural gene drives). The early identification of such issues is relevant to researchers, policy-makers and the wider public.
Simulation models from: Can CRISPER-mediated gene drive work in pest and beneficial haplodiploid species?
11968J. Li and B. Tabashnik, Dryad, 2020-05-26 18:17:03.
Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known about CRISPR gene drive in haplodiploids, despite their immense global impacts as pollinators, pests, natural enemies of pests, and invasive species in native habitats. Here we analyze mathematical models demonstrating that, in principle, CRISPR homing gene drive can work in haplodiploids, as well as at sex-linked loci in diploids. However, relative to diploids, conditions favoring the spread of alleles deleterious to haplodiploid pests by CRISPR gene drive are narrower, the spread is slower, and resistance to the drive evolves faster. By contrast, the spread of alleles that impose little fitness cost or boost fitness was not greatly hindered in haplodiploids relative to diploids. Therefore, altering traits to minimize damage caused by harmful haplodiploids, such as interfering with transmission of plant pathogens, may be more likely to succeed than control efforts based on introducing traits that reduce pest fitness. Enhancing fitness of beneficial haplodiploids with CRISPR gene drive is also promising.
Genetic Biocontrol for Invasive Species
11964J. L. Teem, L. Alphey, S. Descamps, M. P. Edgington, O. Edwards, N. Gemmell, T. Harvey-Samuel, R. L. Melnick, K. P. Oh, A. J. Piaggio, J. R. Saah, D. Schill, P. Thomas, T. Smith and A. Roberts, Frontiers in Bioengineering and Biotechnology, 8:452. 2020-05-25 18:12:26.
Invasive species are increasingly affecting agriculture, food, fisheries, and forestry resources throughout the world. As a result of global trade, invasive species are often introduced into new environments where they become established and cause harm to human health, agriculture, and the environment. Prevention of new introductions is a high priority for addressing the harm caused by invasive species, but unfortunately efforts to prevent new introductions do not address the economic harm that is presently manifested where invasive species have already become established. Genetic biocontrol can be defined as the release of organisms with genetic methods designed to disrupt the reproduction of invasive populations. While these methods offer the potential to control or even eradicate invasive species, there is a need to ensure that genetic biocontrol methods can be deployed in a way that minimizes potential harm to the environment. This review provides an overview of the state of genetic biocontrol, focusing on several approaches that were the subject of presentations at the Genetic Biocontrol for Invasive Species Workshop in Tarragona, Spain, March 31st, 2019, a workshop sponsored by the OECD’s Co-operative Research Program on Biological Resource Management for Sustainable Agricultural Systems. The review considers four different approaches to genetic biocontrol for invasive species; sterile-release, YY Males, Trojan Female Technique, and gene drive. The different approaches will be compared with respect to the efficiency each affords as a genetic biocontrol tool, the practical utility and cost/benefits associated with implementation of the approach, and the regulatory considerations that will need to be addressed for each. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its Member countries.
RNAi: Applications in Vertebrate Pest Management
14854K. E. Horak, Trends in Biotechnology, 38:1200-1202. 2020-05-25 17:42:08.
the development of novel control technologies must be focused on species specificity and low environmental impact. Sequence-specific gene silencing via RNAi holds promise for effective management of pest wildlife.
The Y Chromosome as a Battleground for Intragenomic Conflict
11962D. Bachtrog, Trends in Genetics, 2020-05-21 18:10:11.
Recurrent sex chromosome drive can have profound ecological, evolutionary, and cellular impacts and account for unique features of sex chromosomes.
Gene Drives: Pursuing opportunities, minimizing risk
11966K. L. Warmbrod, A. Kobokovich, R. West, G. Ray, M. Trotochaud and M. Montague, Center for Health Security, 2020-05-18 18:14:50.
This study analyzed the current state of gene drive technologies, the ways in which they might be deployed in the field, and the state of regulatory policy governing their development.
Le forçage génétique (gène drive) et ses applications
18210V. Courtier-Orgogozo, Bulletin de l'Académie Vétérinaire de France, 172:94-98. 2020-05-18 15:11:30.
Gene drive is a new genetic engineering technology that has been developed over the past five years and that allows genetic modifications to spread rapidly in natural populations. Potential applications are numerous, for public health issues, agriculture and conservation biology. This article presents the current developments in this biotechnology, as well as the issues and risks associated with it.
Recessive Z-linked lethals and the retention of haplotype diversity in a captive butterfly population
11972I. J. Saccheri, S. Whiteford, C. J. Yung and A. E. van't Hof, Heredity, 2020-05-13 18:21:56.
Sex chromosomes are predicted to harbour elevated levels of sexually antagonistic variation due to asymmetries in the heritability of recessive traits in the homogametic versus heterogametic sex.
Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations
11548H. M. Sánchez C, J. B. Bennett, S. L. Wu, G. Rašić, O. S. Akbari and J. M. Marshall, BMC Biology, 18:50. 2020-05-12 14:50:48.
Here, we model hypothetical releases of two recently engineered threshold-dependent gene drive systems—reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL—to explore their ability to be confined and remediated.
A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae
11463A. Simoni, A. M. Hammond, A. K. Beaghton, R. Galizi, C. Taxiarchi, K. Kyrou, D. Meacci, M. Gribble, G. Morselli, A. Burt, T. Nolan and A. Crisanti, Nature Biotechnology, 2020-05-11 15:15:55.
We report a male-biased sex-distorter gene drive (SDGD) in the human malaria vector Anopheles gambiae.
Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement
11465A. Hoermann, S. Tapanelli, P. Capriotti, E. K. G. Masters, T. Habtewold, G. K. Christophides and N. Windbichler, bioRxiv, 2020-05-10 15:19:12.
Here we explore how minimal genetic modifications of endogenous mosquito genes can convert them directly into non-autonomous gene drives without disrupting their expression.
Gene drive dynamics in natural populations: The importance of density-dependence, space and sex
11453S. Dhole, A. L. Lloyd and F. Gould, arXiv, arXiv:2005.01838. 2020-05-07 18:26:02.
Here we review how different forms of density-dependence, spatial heterogeneity and mating behaviors can impact the spread of self-sustaining gene drives. We highlight specific aspects of gene drive dynamics and the target populations that need further research.
Beyond limits – the pitfalls of global gene drives for environmental risk assessment in the European Union
11458M. Dolezel, C. Lüthi and H. Gaugitsch, BioRisk, 15:1-29. 2020-05-04 14:58:37.
We evaluate the novel features of GDOs and outline the resulting challenges for the environmental risk assessment.
The development of complex and controversial innovations. Genetically modified mosquitoes for malaria eradication
11431V. Cisnetto and J. Barlow, Research Policy, 49:103917. 2020-05-04 13:32:20.
e use a longitudinal process approach and qualitative system dynamics modelling to study the development of genetically modified (GM) mosquitoes for malaria eradication in an African country.
