Scholarly Literature
This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives). The latest are shown here.
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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.
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