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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The sterile male release approach as a method to control invasive amphibian populations: a preliminary study on Lithobates catesbeianus
13727S. Descamps and A. De Vocht, Management of Biological Invasions, 8:361-370. 2017-09-14 18:55:55.
Widespread populations of the invasive species Lithobates catesbeianus (American bullfrog) are present in different parts of the world and are difficult to control. This study investigated the possibility to sterilize male individuals of this species in order to use the sterile male release technique in controlling these invasive populations.
Using CRISPR-based gene drive for agriculture pest control
13621V. Courtier-Orgogozo, B. Morizot and C. Boëte, EMBO Reports, 18:1481. 2017-09-01 13:15:07.
The authors respond to comments to their publication 10.15252/embr.201744205
The optimal implementation of the Trojan Y chromosome eradication strategy of invasive species
11510M. R. Kelly and X. Y. Wang, Journal of Biological Systems, 25:399-418. 2017-08-02 15:25:17.
Invasive aquatic species continue to be a persistent problem around the world. The Trojan Y Chromosome (TYC) eradication strategy has recently been developed to help fight the problem in aquatic systems by targeting only the invasive species, sparing native marine stock. It involves rearing genetically modified samples of the invasive species and introducing them into the environment to alter the sex ratio of the invasive population. The paper is devoted to finding the optimal implementation of the TYC eradication strategy of an invasive species as well as a modified, potentially more cost-effective strategy. The modified TYC strategy (MTYC) eliminates one round of exposure to sex hormones compared to the TYC strategy. After introducing both strategies, the optimal control problems for each are formulated. The two strategies are compared through numerical simulations. Our results illustrate that the MTYC strategy, with lower implementation costs, is a better strategy option when trying to minimize the overall effective cost in most scenarios.
Illinois study advances possibility of genetic control for major agricultural weeds
11589L. Quinn, ACES News, 2017-07-17 15:35:43.
Waterhemp and Palmer amaranth, two aggressive weeds that threaten the food supply in North America, are increasingly hard to kill with commercially available herbicides. A novel approach known as genetic control could one day reduce the need for these chemicals. Now, scientists are one step closer.
Current vector control challenges in the fight against malaria
16269G. Benelli and J. C. Beier, Acta Tropica, 174:91-96. 2017-07-07 16:47:31.
The majority of National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs). These methods reduce malaria incidence but generally have little impact on malaria prevalence. In addition to outdoor transmission, growing levels of insecticide resistance in targeted vectors threaten the efficacy of LLINs and IRS.
The IAEA and Food – Tsetse Fly Eradication – Senegal
25659International Atomic Energy Agency, IAEA/FAO, 2017-06-21 14:02:20.
Senegal has successfully integrated the Sterile Insect Technique into its tsetse fly control project in the Niayes region. This nuclear technique suppresses or even eradicates insect pest by using radiation to sterilize primarily males. The disease that tsetse flies transmit can kill livestock or make them sick.
Trends in the development of mammalian pest control technology in New Zealand
13735C. T. Eason, L. Shapiro, S. Ogilvie, C. King and M. Clout, New Zealand Journal of Zoology, 44:267-304. 2017-06-19 19:31:49.
The use of new toxins with advantages in specific settings should be complemented by improvements in resetting trap technology, barrier approaches, and novel biocontrol and genetic concepts. Sodium fluoroacetate (1080) and other important tools have been retained; we have the ingredients for transformational change, and new tools are emerging from a research and development pipeline. However, there has been limited practical experience with emerging technologies compared with traditional or 1080 baits.
A maternal-effect selfish genetic element in Caenorhabditis elegans
14450E. Ben-David, A. Burga and L. Kruglyak, Science, 356:1051. 2017-06-09 17:13:17.
We discovered a selfish element causing embryonic lethality in crosses between wild strains of the nematode Caenorhabditis elegans.
Poisons, antidotes, and selfish genes
14448N. Phadnis, Science, 356:1013. 2017-06-09 16:55:51.
On page1051 of this issue, BenDavid et al . (3) chase down a serendipitous observation of an anomaly in genetic crosses to unmask a toxin-antidote type of selfish system in worms.
Agricultural pest control with CRISPR-based gene drive: time for public debate
13636V. Courtier-Orgogozo, B. Morizot and C. Boëte, EMBO Reports, 18:878-880. 2017-06-01 14:19:16.
Gene drive technology to control disease vectors or pests has great potential for addressing humanitarian and public health problems. Its application for pest control in agriculture, however, raises important environmental, social and ethical issues.
A Wolbachia deubiquitylating enzyme induces cytoplasmic incompatibility
5932Beckmann, J. F., J. A. Ronau and M. Hochstrasser, Nature Microbiology, 2:17007. 2017-03-01 17:45:04.
Wolbachia are obligate intracellular bacteria1 that infect arthropods, including approximately two-thirds of insect species2. Wolbachia manipulate insect reproduction by enhancing their inheritance through the female germline. The most common alteration is cytoplasmic incompatibility (CI)3–5, where eggs from uninfected females fail to develop when fertilized by sperm from Wolbachia-infected males. By contrast, if female and male partners are both infected, embryos are viable. CI is a gene-drive mechanism impacting population structure6 and causing reproductive isolation7, but its molecular mechanism has remained unknown. We show that a Wolbachia deubiquitylating enzyme (DUB) induces CI. The CI-inducing DUB, CidB, cleaves ubiquitin from substrates and is encoded in a two-gene operon, and the other protein, CidA, binds CidB. Binding is strongest between cognate partners in cidA-cidB homologues. In transgenic Drosophila, the cidA-cidB operon mimics CI when sperm introduce it into eggs, and a catalytically inactive DUB does not induce sterility. Toxicity is recapitulated in yeast by CidB alone; this requires DUB activity but is rescued by coexpressed CidA. A paralogous operon involves a putative nuclease (CinB) rather than a DUB. Analogous binding, toxicity and rescue in yeast were observed. These results identify a CI mechanism involving interacting proteins that are secreted into germline cells by Wolbachia, and suggest new methods for insect control.
Daisyfield gene drive systems harness repeated genomic elements as a generational clock to limit spread
13623J. Min, C. Noble, D. Najjar and K. M. Esvelt, bioRxiv, 104877. 2017-02-06 13:30:21.
Here we describe a novel form of gene drive based on the introduction of multiple copies of an engineered ‘daisy’ sequence into repeated elements of the genome. Each introduced copy encodes guide RNAs that target one or more engineered loci carrying the CRISPR nuclease gene and the desired traits. When organisms encoding a drive system are released into the environment, each generation of mating with wild-type organisms will reduce the average number of the guide RNA elements per ‘daisyfield’ organism by half, serving as a generational clock
Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates
4063Prowse, TAAC, Phillip; Ross, Joshua V.; Pfitzner, Chandran; Wittmann, Talia A.; Thomas, Paul, Proceedings of the Royal Society B: Biological Sciences, 284:20170799. 2017-01-21 00:00:00.
Self-replicating gene drives that can spread deleterious alleles through animal populations have been promoted as a much needed but controversial ‘silver bullet’ for controlling invasive alien species. Homing-based drives comprise an endonuclease and a guide RNA (gRNA) that are replicated during meiosis via homologous recombination. However, their efficacy for controlling wild populations is threatened by inherent polymorphic resistance and the creation of resistance alleles via non-homologous end-joining (NHEJ)-mediated DNA repair. We used stochastic individual-based models to identify realistic gene-drive strategies capable of eradicating vertebrate pest populations (mice, rats and rabbits) on islands. One popular strategy, a sex-reversing drive that converts heterozygous females into sterile males, failed to spread and required the ongoing deployment of gene-drive carriers to achieve eradication. Under alternative strategies, multiplexed gRNAs could overcome inherent polymorphic resistance and were required for eradication success even when the probability of NHEJ was low. Strategies causing homozygotic embryonic non-viability or homozygotic female sterility produced high probabilities of eradication and were robust to NHEJ-mediated deletion of the DNA sequence between multiplexed endonuclease recognition sites. The latter two strategies also purged the gene drive when eradication failed, therefore posing lower long-term risk should animals escape beyond target islands. Multiplexing gRNAs will be necessary if this technology is to be useful for insular extirpation attempts; however, precise knowledge of homing rates will be required to design low-risk gene drives with high probabilities of eradication success.
How driving endonuclease genes can be used to combat pests and disease vectors
4043Godfray, HCJN, A.; Burt, A., BMC Biology, 15:81. 2017-01-21 00:00:00.
Driving endonuclease genes (DEGs) spread through a population by a non-Mendelian mechanism. In a heterozygote, the protein encoded by a DEG causes a double-strand break in the homologous chromosome opposite to where its gene is inserted and when the break is repaired using the homologue as a template the DEG heterozygote is converted to a homozygote. Some DEGs occur naturally while several classes of endonucleases can be engineered to spread in this way, with CRISPR-Cas9 based systems being particularly flexible. There is great interest in using driving endonuclease genes to impose a genetic load on insects that vector diseases or are economic pests to reduce their population density, or to introduce a beneficial gene such as one that might interrupt disease transmission. This paper reviews both the population genetics and population dynamics of DEGs. It summarises the theory that guides the design of DEG constructs intended to perform different functions. It also reviews the studies that have explored the likelihood of resistance to DEG phenotypes arising, and how this risk may be reduced. The review is intended for a general audience and mathematical details are kept to a minimum.
Is it time for synthetic biodiversity conservation?
4062Piaggio, AJS, G.; Seddon, P. J.; Alphey, L.; Bennett, E. L.; Carlson, R. H.; Friedman, R. M.; Kanavy, D.; Phelan, R.; Redford, K. H.; Rosales, M.; Slobodian, L.; Wheeler, K., Trends in Ecology & Evolution, 32:97-107. 2017-01-20 00:00:00.
Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology.
Precaution: Open gene drive research
4042Esvelt, KM, Science, 355:589-590. 2017-01-20 00:00:00.
IN THEIR POLICY Forum “Precaution and governance of emerging technologies” (11 November 2016, p. 710), G. E. Kaebnick and colleagues convincingly assert that precaution is consistent with support for science. However, they overlook one way to improve safety while hastening discovery: Make research open.
Ethical implications of fighting malaria with CRISPR/Cas9
4061Patrão Neves, MD, Christiane, BMJ Global Health, 2:e000396. 2017-01-19 00:00:00.
Genome editing is a new, cheap and versatile technique which has great promise to combat vector-borne diseases. The current ethical debate worldwide is mainly concentrating on the dangers of germline intervention and less so on the potential for fighting vector-borne diseases. ; Gene drive technology has been significantly boosted by the CRISPR/Cas9 gene editing tool which may be able to combat malaria by targeting specific stretches of vector DNA and editing genomes at precise locations, working like a molecular scissors. However, CRISPR/Cas9 is currently not a ‘silver bullet’ and needs further research and consideration of the ethical aspects and consequences of its use.; In September 2016, the UNESCO Chair of Bioethics at the Medical University of Vienna convened a meeting entitled ‘Fighting Malaria with CRISPR/ Cas9: Ethical Implications’, which gathered together infectious disease experts with a focus on malaria, entomologists and ethicists to discuss the advantages and disadvantages of genome editing applied to mosquitoes to fight malaria. ; Although there was no formal consensus, some general conclusions were reached, in particular that any ethical debate needs to involve African stakeholders living in malaria areas and to consider future generations and the environment. The precautionary principle should be taken into account in any discussion, as should be the human cost of doing nothing.
Principles for gene drive research
4041Emerson, CJ, Stephanie; Littler, Katherine; Randazzo, Filippo, Science, 358:1135. 2017-01-19 00:00:00.
The recent outbreak of Zika virus in the Americas renewed attention on the importance of vector-control strategies to fight the many vector-borne diseases that continue to inflict suffering around the world. In 2015, there were ?212 million infections and a death every minute from malaria alone (1). Gene drive technology is being explored as a potentially durable and cost-effective strategy for controlling the transmission of deadly and debilitating vector-borne diseases that affect millions of people worldwide, such as Zika virus and malaria. Additionally, its suitability is being evaluated for various potential applications in conservation biology, including a highly specific and humane method for eliminating invasive species from sensitive ecosystems (2, 3).
Conditions for success of engineered underdominance gene drive systems
4040Edgington, MPA, L. S., Journal of Theoretical Biology, 430:128-140. 2017-01-18 00:00:00.
Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually suppressing lethals. In such a system two genetic constructs are introduced, each possessing a lethal element and a suppressor of the lethal at the other locus. Specifically, we formulate and analyse a population genetics model of this system to assess when different combinations of release strategies (i.e. single or multiple releases of both sexes or males only) and genetic systems (i.e. bisex lethal or female-specific lethal elements and different strengths of suppressors) will give population replacement or fail to do so. We anticipate that results presented here will inform the future design of engineered underdominance gene drive systems as well as providing a point of reference regarding release strategies for those looking to test such a system. Our discussion is framed in the context of genetic control of insect vectors of disease. One of several serious threats in this context are Aedes aegypti mosquitoes as they are the primary vectors of dengue viruses. However, results are also applicable to Ae. aegypti as vectors of Zika, yellow fever and chikungunya viruses and also to the control of a number of other insect species and thereby of insect-vectored pathogens.
wtf genes are prolific dual poison-antidote meiotic drivers
4060Nuckolls, NLN, M. A. B.; Eickbush, M. T.; Young, J. M.; Lange, J. J.; Yu, J. S.; Smith, G. R.; Jaspersen, S. L.; Malik, H. S.; Zanders, S. E., eLife, 6:e26033. 2017-01-18 00:00:00.
Meiotic drivers are selfish genes that bias their transmission into gametes, defying Mendelian inheritance. Despite the significant impact of these genomic parasites on evolution and infertility, few meiotic drive loci have been identified or mechanistically characterized. Here, we demonstrate a complex landscape of meiotic drive genes on chromosome 3 of the fission yeasts Schizosaccharomyces kambucha and S. pombe. We identify S. kambucha wtf4 as one of these genes that acts to kill gametes (known as spores in yeast) that do not inherit the gene from heterozygotes. wtf4 utilizes dual, overlapping transcripts to encode both a gamete-killing poison and an antidote to the poison. To enact drive, all gametes are poisoned, whereas only those that inherit wtf4 are rescued by the antidote. Our work suggests that the wtf multigene family proliferated due to meiotic drive and highlights the power of selfish genes to shape genomes, even while imposing tremendous costs to fertility.
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