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.
Integral gene drives for population replacement
3930Nash, AU, Giulia Mignini; Beaghton, Andrea K.; Hoermann, Astrid; Papathanos, Philippos Aris; Christophides, George K.; Windbichler, Nikolai, Biology Open, 8:bio037762. 2019-01-08 00:00:00.
A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. We have evaluated theoretically the concept of integral gene drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including drive and anti-pathogen effector elements directly embedded within endogenous genes – an arrangement that in theory allows targeting functionally conserved coding sequences without disrupting their function. Autonomous and non-autonomous IGD strains could be generated, optimized, regulated and imported independently. We performed quantitative modeling comparing IGDs with classical replacement drives and show that selection for the function of the hijacked host gene can significantly reduce the establishment of resistant alleles in the population, while drive occurring at multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target site variation. IGD thus has potential as a more durable and flexible population replacement strategy.
Large-cage assessment of a transgenic sex-ratio distortion strain on populations of an African malaria vector
3910Facchinelli, LN, A.; Collins, C.; Menichelli, M.; Persampieri, T.; Bucci, A.; Spaccapelo, R.; Crisanti, A.; Benedict, M., Parasites & Vectors, 12:70. 2019-01-08 00:00:00.
Novel transgenic mosquito control methods require progressively more realistic evaluation. The goal of this study was to determine the effect of a transgene that causes a male-bias sex ratio on Anopheles gambiae target populations in large insectary cages. Life history characteristics of Anopheles gambiae wild type and Ag(PMB)1 (aka (gfp)124L-2) transgenic mosquitoes, whose progeny are 95% male, were measured in order to parameterize predictive population models. Ag(PMB)1 males were then introduced at two ratios into large insectary cages containing target wild type populations with stable age distributions and densities. The predicted proportion of females and those observed in the large cages were compared. A related model was then used to predict effects of male releases on wild mosquitoes in a west African village. The frequency of transgenic mosquitoes in target populations reached an average of 0.44 +/- 0.02 and 0.56 +/- 0.02 after 6 weeks in the 1:1 and in the 3:1 release ratio treatments (transgenic male:wild male) respectively. Transgenic males caused sex-ratio distortion of 73% and 80% males in the 1:1 and 3:1 treatments, respectively. The number of eggs laid in the transgenic treatments declined as the experiment progressed, with a steeper decline in the 3:1 than in the 1:1 releases. The results of the experiment are partially consistent with predictions of the model; effect size and variability did not conform to the model in two out of three trials, effect size was over-estimated by the model and variability was greater than anticipated, possibly because of sampling effects in restocking. The model estimating the effects of hypothetical releases on the mosquito population of a West African village demonstrated that releases could significantly reduce the number of females in the wild population. The interval of releases is not expected to have a strong effect. The biological data produced to parameterize the model, the model itself, and the results of the experiments are components of a system to evaluate and predict the performance of transgenic mosquitoes. Together these suggest that the Ag(PMB)1 strain has the potential to be useful for reversible population suppression while this novel field develops.
Problem formulation for gene drive mosquitoes designed to reduce malaria transmission in Africa: results from four regional consultations 2016–2018
3950Teem, JLA, Aggrey; Glover, Barbara; Ouedraogo, Jeremy; Makinde, Diran; Roberts, Andrew, Malaria Journal, 18:347. 2019-01-08 00:00:00.
Gene drive mosquitoes have been proposed as a possible means to reduce the transmission of malaria in Africa. Because this technology has no prior use-history at this time, environmental risk assessments for gene drive mosquitoes will benefit from problem formulation—an organized and ordered process to identify protection goals and potential pathways to harm to the environment, or animal or human health. Recognizing this need, the New Partnership for Africa’s Development (NEPAD), with support from African and international partners, organized four regional consultative workshops in Africa to initiate this process.
The Release of Genetically Engineered Mosquitoes in Burkina Faso: Bioeconomy of Science, Public Engagement and Trust in Medicine
3890Beisel, UG, J. K., African Studies Review, 62:164-173. 2019-01-08 00:00:00.
Malaria, which is transmitted by mosquitoes, continues to be responsible for a significant number of disease episodes and childhood deaths on the African continent. A variety of mosquito control strategies are currently inplace, but since case numbers are rising again, and drug and insecticide tolerance slow down progress made, there has been a push for innovative strategies. In August 2018, the National Biosafety Agency of Burkina Faso granted approval for the release of a maximum of 10,000 male Anopheles mosquitoes in experimental trials conducted by the multi-country consortium Target Malaria. These mosquitoes are rendered infertile through genetic modification, namely through “re-programming” of endonucleases that “cut through essential genes,” in this case, genes for fertility (Target Malaria 2019). The idea is that through the sterilization of male mosquitoes, the population of malaria-transmitting mosquitoes will be reduced, thereby decreasing the overall number of malaria infections.
Conserving New Zealand’s native fauna: a review of tools being developed for the Predator Free 2050 programme
3929Murphy, ECR, J. C.; Broome, K. G.; Ryan, G. J.; Dowding, J. E., Journal of Ornithology, 160:883-892. 2019-01-07 00:00:00.
The endemic fauna of New Zealand evolved in the absence of mammalian predators and the introduction of the latter has been devastating. There have been numerous avian extinctions and 80% of the extant native avian taxa are currently threatened or at risk of extinction. Declines continue, and a fundamental change in predator management is required. In 2016 came the announcement of the ambitious Predator Free 2050 (PF 2050) programme, which aims to eradicate rats, mustelids, and Brushtail Possums from New Zealand by 2050. This paper reviews some of the many techniques being discussed or developed to implement the programme. Existing techniques are being refined and new tools are being developed. Research on new toxins, including those with potentially higher species specificity, is under way, and novel baits and toxin-delivery devices are being developed. Existing trap designs are being refined, and new self-resetting traps capable of multiple kills have been developed. Research is also under way on new lures and repellents. Eradications may be achieved in stages, and barriers (both natural and artificial) will be needed to protect areas already cleared. Current techniques will probably be inadequate to effect nationwide eradications, and new tools (possibly based on genetic technologies) will probably be required. Regulatory hurdles will need to be overcome, and community consultation and support (social licence) will be required throughout the programme. The use of some new technologies may be contentious, and not every new idea will necessarily be adopted. Technical, social, and organisational challenges exist, and national and international collaboration will be required for PF 2050 to succeed.
Making a murderer: The evolutionary framing of hybrid gamete-killers
3949Sweigart, ALB, Yaniv; Fishman, Lila, Trends in Genetics, 35:245-252. 2019-01-07 00:00:00.
Recent molecular investigations of hybrid incompatibilities have revealed fascinating patterns of genetic interactions that have been interpreted as the remnants of a history of selfish evolution. Instead of framing hybrid incompatibilities in light of genetic conflict, we advocate assuming their innocence. Researchers must build a strong theory for each case, supported by population genetic evidence, such that the role of conflict in the evolution of a hybrid incompatibility can be proven beyond reasonable doubt. This will require careful investigation of the evolutionary history of these incompatibilities, a reckoning of how the reproductive biology of study organisms impacts on the likelihood of genetic conflict, and molecular evidence of the rapid selfish spread of these alleles.
Modeling the mutation and reversal of engineered underdominance gene drives
3909Edgington, MPA, Luke S., Journal of Theoretical Biology, 479:14-21. 2019-01-07 00:00:00.
A range of gene drive systems have been proposed that are predicted to increase their frequency and that of associated desirable genetic material even if they confer a fitness cost on individuals carrying them. Engineered underdominance (UD) is such a system and, in one version, is based on the introduction of two independently segregating transgenic constructs each carrying a lethal gene, a suppressor for the lethal at the other locus and a desirable genetic “cargo”. Under this system individuals carrying at least one copy of each construct (or no copies of either) are viable whilst those that possess just one of the transgenic constructs are non-viable. Previous theoretical work has explored various properties of these systems, concluding that they should persist indefinitely in absence of resistance or mutation. Here we study a population genetics model of UD gene drive that relaxes past assumptions by allowing for loss-of-function mutations in each introduced gene. We demonstrate that mutations are likely to cause UD systems to break down, eventually resulting in the elimination of introduced transgenes. We then go on to investigate the potential of releasing “free suppressor” carrying individuals as a new method for reversing UD gene drives and compare this to the release of wild-types; the only previously proposed reversal strategy for UD. This reveals that while free suppressor carrying individuals may represent an inexpensive reversal strategy due to extremely small release requirements, they are not able to return a fully wild-type population as rapidly as the release of wild-types.
The toxin–antidote model of cytoplasmic incompatibility: Genetics and evolutionary implications
3889Beckmann, JFB, Manon; Chen, Hongli; Hochstrasser, Mark; Poinsot, Denis; Merçot, Hervé; Weill, Mylène; Sicard, Mathieu; Charlat, Sylvain, Trends in Genetics, 35:175-185. 2019-01-07 00:00:00.
Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of these and constitutes a promising weapon against vector-borne diseases. After decades of theoretical and experimental struggle, major recent advances have been made toward a molecular understanding of this phenomenon. As pieces of the puzzle come together, from yeast and Drosophila fly transgenesis to CI diversity patterns in natural mosquito populations, it becomes clearer than ever that the CI induction and rescue stem from a toxin–antidote (TA) system. Further, the tight association of the CI genes with prophages provides clues to the possible evolutionary origin of this phenomenon and the levels of selection at play.
Gene drive for population genetic control: non-functional resistance and parental effects
3888Beaghton, AKH, Andrew; Nolan, Tony; Crisanti, Andrea; Burt, Austin, Proceedings of the Royal Society B: Biological Sciences, 286:20191586. 2019-01-06 00:00:00.
Gene drive is a natural process of biased inheritance that, in principle, could be used to control pest and vector populations. As with any form of pest control, attention should be paid to the possibility of resistance evolving. For nuclease-based gene drive aimed at suppressing a population, resistance could arise by changes in the target sequence that maintain function, and various strategies have been proposed to reduce the likelihood that such alleles arise. Even if these strategies are successful, it is almost inevitable that alleles will arise at the target site that are resistant to the drive but do not restore function, and the impact of such sequences on the dynamics of control has been little studied. We use population genetic modelling of a strategy targeting a female fertility gene to demonstrate that such alleles may be expected to accumulate, and thereby reduce the reproductive load on the population, if nuclease expression per se causes substantial heterozygote fitness effects or if parental (especially paternal) deposition of nuclease either reduces offspring fitness or affects the genotype of their germline. All these phenomena have been observed in synthetic drive constructs. It will, therefore, be important to allow for non-functional resistance alleles in predicting the dynamics of constructs in cage populations and the impacts of any field release.
Governing extinction in the era of gene editing
3928Monast, JJ, North Carolina Law Review, 97:1329-1358. 2019-01-06 00:00:00.
CRISPR-Cas9 genome-editing technology (“CRISPR”) offers a potential solution for some of the world’s critical conservation challenges. Scientists are harnessing CRISPR to expand genetic diversity of endangered species, control invasive species, or enhance species’ resiliency to a changing climate. Recreating extinct species is now realistic, as is engineering entirely new species. CRISPR also creates opportunities to address vector-borne infectious diseases such as malaria, dengue fever, and Zika using gene drive techniques that can spread genetic alterations through populations. ; While CRISPR is a powerful tool to address public health and conservation goals, it could allow scientists to bypass longstanding value choices underlying national and international conservation efforts and foster permanent ecosystem impacts before public policy can react. This Article argues that, while current conservation laws do not directly address many of the specific questions that arise with CRISPR, the Endangered Species Act (“ESA”) establishes a framework that can, and should, guide the use of gene editing. The proposal calls for: (1) a presumption against the release of genetically modified organisms that could cause species extinction, (2) exemptions for specific public health and environmental goals, and (3) updates to the ESA to clarify oversight of gene editing.
Locally Fixed Alleles: A method to localize gene drive to island populations
3948Sudweeks, JH, Brandon; Blondel, Dimitri V.; Campbell, Karl J.; Dhole, Sumit; Eisemann, John D.; Edwards, Owain; Godwin, John; Howald, Gregg R.; Oh, Kevin P.; Piaggio, Antoinette J.; Prowse, Thomas A. A.; Ross, Joshua V.; Saah, J. Royden; Shiels, Aaron B.; Thomas, Paul Q.; Threadgill, David W.; Vella, Michael R.; Gould, Fred; Lloyd, Alun L., Scientific Reports, 9:15821. 2019-01-06 00:00:00.
Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to alleles at multiple genomic loci becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.
Using problem formulation for fit-for-purpose pre-market environmental risk assessments of regulated stressors
3908Devos, YC, W.; Devlin, R. H.; Ippolito, A.; Leggatt, R. A.; Romeis, J.; Shaw, R.; Svendsen, C.; Topping, C. J., EFSA Journal, 17:e170708. 2019-01-06 00:00:00.
Pre-market/prospective environmental risk assessments (ERAs) contribute to risk analyses performed to facilitate decisions about the market introduction of regulated stressors. Robust ERAs begin with an explicit problem formulation, which involves among other steps: (1) formally devising plausible pathways to harm that describe how the deployment of a regulated stressor could be harmful; (2) formulating risk hypotheses about the likelihood and severity of such events; (3) identifying the information that will be useful to test the risk hypotheses; and (4) developing a plan to acquire new data for hypothesis testing should tests with existing information be insufficient for decision-making. Here, we apply problem formulation to the assessment of possible adverse effects of RNA interference-based insecticidal genetically modified (GM) plants, GM growth hormone coho salmon, gene drive-modified mosquitoes and classical biological weed control agents on non-target organisms in a prospective manner, and of neonicotinoid insecticides on bees in a retrospective manner. In addition, specific considerations for the problem formulation for the ERA of nanomaterials and for landscape-scale population-level ERAs are given. We argue that applying problem formulation to ERA maximises the usefulness of ERA studies for decision-making, through an iterative process, because: (1) harm is defined explicitly from the start; (2) the construction of risk hypotheses is guided by policy rather than an exhaustive attempt to address any possible differences; (3) existing information is used effectively; (4) new data are collected with a clear purpose; (5) risk is characterised against well-defined criteria of hypothesis corroboration or falsification; and (6) risk assessment conclusions can be communicated clearly. However, problem formulation is still often hindered by the absence of clear policy goals and decision-making criteria (e.g. definition of protection goals and what constitutes harm) that are needed to guide the interpretation of scientific information. We therefore advocate further dialogue between risk assessors and risk managers to clarify how ERAs can address policy goals and decision-making criteria. Ideally, this dialogue should take place for all classes of regulated stressors, as this can promote alignment and consistency on the desired level of protection and maximum tolerable impacts across regulated stressors. (C) 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.
Controlling invasive rodents via synthetic gene drive and the role of polyandry
3927Manser, AC, S. J.; Sutter, A.; Blondel, D. V.; Serr, M.; Godwin, J.; Price, T. A. R., Proceedings of the Royal Society B-Biological Sciences, 286:9. 2019-01-05 00:00:00.
House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male's sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three-to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design.
Gene drives in plants: opportunities and challenges for weed control and engineered resilience
3887Barrett, LGL, Mathieu; Kumaran, Nagalingam; Glassop, Donna; Raghu, S.; Gardiner, Donald M., Proceedings of the Royal Society B: Biological Sciences, 286:9. 2019-01-05 00:00:00.
Plant species, populations and communities are under threat from climate change, invasive pathogens, weeds and habitat fragmentation. Despite considerable research effort invested in genome engineering for crop improvement, the development of genetic tools for the management of wild plant populations has rarely been given detailed consideration. Gene drive systems that allow direct genetic management of plant populations via the spread of fitness-altering genetic modifications could be of great utility. However, despite the rapid development of synthetic tools and their enormous promise, little explicit consideration has been given to their application in plants and, to date, they remain untested. This article considers the potential utility of gene drives for the management of wild plant populations, and examines the factors that might influence the design, spread and efficacy of synthetic drives. To gain insight into optimal ways to design and deploy synthetic drive systems, we investigate the diversity of mechanisms underlying natural gene drives and their dynamics within plant populations and species. We also review potential approaches for engineering gene drives and discuss their potential application to plant genomes. We highlight the importance of considering the impact of plant life-history and genetic architecture on the dynamics of drive, investigate the potential for different types of resistance evolution, and touch on the ethical, regulatory and social challenges ahead.
Gene driving the farm: who decides, who owns, and who benefits?
3907Montenegro de Wit, M, Agroecology and Sustainable Food Systems, 43:1054-1074. 2019-01-05 00:00:00.
This commentary essay explores the social and ecological implications of gene-driving agriculture.
Genetic manipulation of sex ratio in mammals: the Reaper comes for Mickey
3947Smanski, MJZ, David, EMBO reports, 20:e48577. 2019-01-05 00:00:00.
In most animals, sexual reproduction results in a 1:1 ratio of females to males. For several sectors of agriculture, for example, milk or egg production, only a single sex is needed. Biasing the sex ratio so that only offspring of the desired sex are produced has the potential to increase breeding efficiency. In this issue of EMBO Reports, Yosef et al [1] demonstrate a genetic approach to bias the sex ratio in mice by specifically disrupting essential genes in male embryos. Their approach is an important first step toward generating sex-ratio biasing applications for agriculture
Construction of an efficient genomic editing system with CRISPR/Cas9 in the vector mosquito Aedes albopictus
3926Liu, TY, W. Q.; Xie, Y. G.; Liu, P. W.; Xie, L. H.; Lin, F.; Li, C. Y.; Gu, J. B.; Wu, K.; Yan, G. Y.; Chen, X. G., Insect Science, 26:1045-1054. 2019-01-04 00:00:00.
Aedes (Stegomyia) albopictus, also known as the Asian tiger mosquito, is a mosquito which originated in Asia. In recent years, it has become increasingly rampant throughout the world. This mosquito can transmit several arboviruses, including dengue, Zika and chikungunya viruses, and is considered a public health threat. Despite the urgent need of genome engineering to analyze specific gene functions, progress in genetical manipulation of Ae. albopictus has been slow due to a lack of efficient methods and genetic markers. In the present study, we established targeted disruptions in two genes, kynurenine hydroxylase (kh) and dopachrome conversion enzyme (yellow), to analyze the feasibility of generating visible phenotypes with genome editing by the clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated protein 9 (Cas9) system in Ae. albopictus. Following Cas9 single guide RNA ribonucleoprotein injection into the posterior end of pre-blastoderm embryos, 30%-50% of fertile survivors produced alleles that failed to complement existing kh and yellow mutations. Complete eye and body pigmentation defects were readily observed in G1 pupae and adults, indicating successful generation of highly heritable mutations. We conclude that the CRISPR/Cas9-mediated gene editing system can be used in Ae. albopictus and that it can be adopted as an efficient tool for genome-scale analysis and biological study.
Sustainability as a framework for considering gene drive mice for invasive rodent eradication
3886Barnhill-Dilling, SKS, M.; Blondel, D. V.; Godwin, J., Sustainability, 11:1334. 2019-01-04 00:00:00.
Gene drives represent a dynamic and controversial set of technologies with applications that range from mosquito control to the conservation of biological diversity on islands. Currently, gene drives are being developed in mice that may one day serve as an important tool for reducing invasive rodent pests, a key threat to island biodiversity and economies. Gene drives in mice are still in development in laboratories, and wild release of modified mice is likely a distant reality. However, technological changes outpace the existing capacity of regulatory frameworks, and thus require integrated governance frameworks. We suggest sustainability-which gives equal consideration to the environment, economy, and society-as one framework for addressing complexity and uncertainty in the governance of emerging gene drive technologies for invasive species management. We explore the impacts of rodent gene drives on island environments, including potential conservation and restoration of island biodiversity. We outline considerations for rodent gene drives on island economies, including impacts on agricultural and tourism losses, and reductions in biosecurity costs. Finally, we address the social dimension as an essential space for deliberation that will be integral to evaluating the potential deployment of gene drive rodents on islands.
Targeting female reproduction in insects with biorational insecticides for pest management: a critical review with suggestions for future research
3946Smagghe, GZ, M.; Retnakaran, A., Current Opinion in Insect Science, 31:65-69. 2019-01-04 00:00:00.
Of the different approaches to pest control, use of juvenile hormone analogs (e.g. methoprene), molting hormone (20-hydroxyecdysone) analogs (e.g. tebufenozide) and chitin synthesis inhibitors (e.g. diflubenzuron) has dominated this field. Since they adversely interfere with the normal growth and development in one way or another, they have been collectively called as 'insect growth regulators' or IGRs. A lesser known fact is that they all have deleterious effects on reproduction as well as act as ovicides. The raison d'etre for this review is to summarize what we have learnt during the last 3-4 decades in the use of these IGRs, how they affect insect reproduction and how we can apply this knowledge to control pest insects. Finally, we present, information on the state of the art use of molecular technologies such as RNAi and CRISPR/Cas9 applications for pest management targeting insect reproduction.
The ethics of genome editing in non-human animals: a systematic review of reasons reported in the academic literature
3906de Graeff, NJ, K. R.; Johnston, J.; Hartley, S.; Bredenoord, A. L., Philosophical Transactions of the Royal Society B-Biological Sciences, 374:1-25. 2019-01-04 00:00:00.
In recent years, new genome editing technologies have emerged that can edit the genome of non-human animals with progressively increasing efficiency. Despite ongoing academic debate about the ethical implications of these technologies, no comprehensive overview of this debate exists. To address this gap in the literature, we conducted a systematic review of the reasons reported in the academic literature for and against the development and use of genome editing technologies in animals. Most included articles were written by academics from the biomedical or animal sciences. The reported reasons related to seven themes: human health, efficiency, risks and uncertainty, animal welfare, animal dignity, environmental considerations and public acceptability. Our findings illuminate several key considerations about the academic debate, including a low disciplinary diversity in the contributing academics, a scarcity of systematic comparisons of potential consequences of using these technologies, an underrepresentation of animal interests, and a disjunction between the public and academic debate on this topic. As such, this article can be considered a call for a broad range of academics to get increasingly involved in the discussion about genome editing, to incorporate animal interests and systematic comparisons, and to further discuss the aims and methods of public involvement. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'.
Gene conversion generates evolutionary novelty that fuels genetic conflicts
3905Daugherty, MDZ, Sarah E., Current Opinion in Genetics & Development, 58-59:49-54. 2019-01-03 00:00:00.
Genetic conflicts arise when the evolutionary interests of two genetic elements are not aligned. Conflicts between genomes (e.g. pathogen versus host) or within the same genome (e.g. internal parasitic DNA sequences versus the rest of the host genome) can both foster ‘molecular arms races’, in which genes on both sides of the conflict rapidly evolve due to bouts of adaptation and counter-adaptation. Importantly, a source of genetic novelty is needed to fuel these arms races. In this review, we highlight gene conversion as a major force in generating the novel alleles on which selection can act. Using examples from both intergenomic and intragenomic conflicts, we feature the mechanisms by which gene conversion facilitates the rapid evolution of genes in conflict.
Informed consent and community engagement in open field research: lessons for gene drive science
3945Singh, JA, BMC Medical Ethics, 20:54. 2019-01-03 00:00:00.
The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene drive constructs to reduce or suppress mosquito populations to levels that do not support disease transmission. Despite this prospect, social resistance to genetically modified organisms remains high. Gene drive open field research thus raises important questions regarding what is owed to those who may not consent to such research, or those could be affected by the proposed research, but whose consent is not solicited. The precise circumstances under which informed consent must be obtained, and from whom, requires careful consideration. Furthermore, appropriate engagement processes should be central to any introduction of genetically modified mosquitos in proposed target settings.
Next-generation CRISPR-based gene drive supports genetic editing with selective precision
3885Anonymous, International Sugar Journal, 121:411-412. 2019-01-03 00:00:00.
New CRISPR-based gene drives and broader active genetics technologies are revolutionizing the way scientists engineer the transfer of specific traits from one generation to another.
Two minutes to midnight-what international law can do about genome editing
3925Lee, TL, Asian Journal of Wto & International Health Law and Policy, 14:227-265. 2019-01-03 00:00:00.
With its ability to transform the ecosystem, gene drives, a powerful genome-editing technology, poses nuanced regulatory challenges. In particular, as gene drives can override the normal rule of inheritance, where the impacts of gene-drive modified organisms on the environment could be irreversible, leading to a permanent population change. Moreover, as these gene-drive modified organisms are designed to spread to large populations, they can also penetrate national and geographic borders, with global implications. Insofar as gene drive applications could be both potentially beneficial as well as hazardous to the world, this article seeks to explore ways in which international law could provide a useful platform to engage the relevant stakeholders in general, and encourage responsible science in specific.
Alternative strategies for mosquito-borne arbovirus control
3884Achee, NLG, J. P.; Vatandoost, H.; Seixas, G.; Pinto, J.; Ching-Ng, L.; Martins, A. J.; Juntarajumnong, W.; Corbel, V.; Gouagna, C.; David, J. P.; Logan, J. G.; Orsborne, J.; Marois, E.; Devine, G. J.; Vontas, J., PLOS Neglected Tropical Diseases, 13:e0006822. 2019-01-02 00:00:00.
Mosquito-borne virusessuch as Zika, chikungunya, dengue fever, and yellow fever, among othersare of global importance. Although vaccine development for prevention of mosquito-borne arbovirus infections has been a focus, mitigation strategies continue to rely on vector control. However, vector control has failed to prevent recent epidemics and arrest expanding geographic distribution of key arboviruses, such as dengue. As a consequence, there has been increasing necessity to further optimize current strategies within integrated approaches and advance development of alternative, innovative strategies for the control of mosquito-borne arboviruses. Methods and findings This review, intended as a general overview, is one of a series being generated by the Worldwide Insecticide resistance Network (WIN). The alternative strategies discussed reflect those that are currently under evaluation for public health value by the World Health Organization (WHO) and represent strategies of focus by globally recognized public health stakeholders as potential insecticide resistance (IR)-mitigating strategies. Conditions where these alternative strategies could offer greatest public health value in consideration of mitigating IR will be dependent on the anticipated mechanism of action. Arguably, the most pressing need for endorsement of the strategies described here will be the epidemiological evidence of a public health impact. Conclusions As the burden of mosquito-borne arboviruses, predominately those transmitted by Aedes aegypti and A. albopictus, continues to grow at a global scale, new vector-control tools and integrated strategies will be required to meet public health demands. Decisions regarding implementation of alternative strategies will depend on key ecoepidemiological parameters that each is intended to optimally impact toward driving down arbovirus transmission. Author summary International public health workers are challenged by the burden of arthropod-borne viral diseases, to include mosquito-borne arboviruses transmitted by Aedes aegypti and A. albopictus due in part to lack of sustainable vector control and insecticide resistance (IR), as well as the inability to scale up and sustain existing interventions for prevention of urban epidemics. As a consequence, there has been increasing interest to advance the development of alternative methods. This review provides a general overview of alternative vector-control strategies under development for the control of arbovirus mosquito vectors and highlights how each could offer innovative public health value. Considerations to regulations, acceptance, and sustainability are also provided.
Biocontrol in Australia: Can a carp herpesvirus (CyHV-3) deliver safe and effective ecological restoration?
3924Kopf, RKB, M.; Finlayson, C. M.; Hodges, K.; Humphries, P.; King, A.; Kingsford, R. T.; Marshall, J.; McGinness, H. M.; Thresher, R.; Vanderplasschen, A., Biological Invasions, 21:1857-1870. 2019-01-02 00:00:00.
The Australian Government is considering Cyprinid herpesvirus 3 (CyHV-3) for biocontrol of invasive common carp (Cyprinus carpio L.). We review the evidence-base for its potential ecological risks, benefits and effectiveness. Lower carp abundance may boost native fish biomass and improve water clarity, but there is little evidence available to suggest that the virus, alone or used in combination with other methods, can deliver effective or safe biocontrol. Further, the virus may already be present in Australia. Overseas, the virus has caused sporadic and localized mortalities of carp in lakes and rivers, but has generally had no long-term measurable effect on wild carp or native fish populations. The temperature range of disease (18-28 degrees C), unknown co-factors causing outbreaks, and predictable re-colonization and recruitment boom of immune and virus-resistant carp, following a biocontrol release, remain formidable and unmitigated barriers to success. CyHV-3 infection trials on Australian biota have unexplained high mortality rates of recreationally-important and threatened fishes, and the role of asymptomatic carriers remains uncertain. Finally, Australia has national and international obligations to ensure that there are no perverse outcomes from biocontrol actions. Despite political pressure, there is no environmental justification to rush the release of this virus. To achieve the Government goals of restoring native biodiversity we advocate that key uncertainties, risks and efficacy barriers first need to be addressed. It is only then that viral biocontrol could be considered a viable tool to complement broader ecological restoration strategies for Australia's waterways.
Evaluating the Probability of CRISPR-based Gene Drive Contaminating Another Species
3904Courtier-Orgogozo, VD, Antoine; Gouyon, Pierre-Henri; Boëte, Christophe, bioRxiv, 776609:27. 2019-01-02 00:00:00.
The probability D that a given CRISPR-based gene drive element contaminates another, non-target species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: D = (hyb+transf).express.cut.flank.immune.nonextinct withhyb = probability of hybridization between the target species and a non-target speciestransf = probability of horizontal transfer of a piece of DNA containing the gene drive cassette from the target species to a non-target species (with no hybridization)express = probability that the Cas9 and guide RNA genes are expressedcut = probability that the CRISPR-guide RNA recognizes and cuts at a DNA site in the new hostflank = probability that the gene drive cassette inserts at the cut siteimmune = probability that the immune system does not reject Cas9-expressing cellsnonextinct = probability of invasion of the drive within the population We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans. We conclude from current data that the probability of a gene drive cassette to contaminate another species is not insignificant. We propose strategies to reduce this risk and call for more work on estimating all the parameters of the formula.CRISPRClustered Regularly Interspaced Short Palindromic RepeatsDRAQUEDrive Risk Assessment Quantitative EstimateHGThorizontal gene transferHTThorizontal transfer of transposable elementTEtransposable element
Two-By-One model of cytoplasmic incompatibility: Synthetic recapitulation by transgenic expression of cifA and cifB in Drosophila
3944Shropshire, JDB, S. R., PLOS Genetics, 15:e1008221. 2019-01-02 00:00:00.
Wolbachia are maternally inherited bacteria that infect arthropod species worldwide and are deployed in vector control to curb arboviral spread using cytoplasmic incompatibility (CI). CI kills embryos when an infected male mates with an uninfected female, but the lethality is rescued if the female and her embryos are likewise infected. Two phage WO genes, cifA(wMel) and cifB(wMel) from the wMel Wolbachia deployed in vector control, transgenically recapitulate variably penetrant CI, and one of the same genes, cifA(wMel), rescues wild type CI. The proposed Two-by-One genetic model predicts that CI and rescue can be recapitulated by transgenic expression alone and that dual cifA(wMel) and cifB(wMel) expression can recapitulate strong CI. Here, we use hatch rate and gene expression analyses in transgenic Drosophila melanogaster to demonstrate that CI and rescue can be synthetically recapitulated in full, and strong, transgenic CI comparable to wild type CI is achievable. These data explicitly validate the Two-by-One model in wMel-infected D. melanogaster, establish a robust system for transgenic studies of CI in a model system, and represent the first case of completely engineering male and female animal reproduction to depend upon bacteriophage gene products. Author summary Releases of Wolbachia-infected mosquitos are underway worldwide because Wolbachia block replication of Zika and Dengue viruses and spread themselves maternally through arthropod populations via cytoplasmic incompatibility (CI). The CI drive system depends on a Wolbachia-induced sperm modification that results in embryonic lethality when an infected male mates with an uninfected female, but this lethality is rescued when the female and her embryos are likewise infected. We recently reported that the phage WO genes, cifA and cifB, cause the sperm modification and cifA rescues the embryonic lethality caused by the wMel Wolbachia strain deployed in vector control. These reports motivated proposal of the Two-by-One model of CI whereby two genes cause lethality and one gene rescues it. Here we provide unequivocal support for the model in the Wolbachia strain used in vector control via synthetic methods that recapitulate CI and rescue in the absence of a Wolbachia infections. Our results reveal the set of phage WO genes responsible for this powerful genetic drive system, act as a proof-of-concept that these genes alone can induce gene drive like crossing patterns, and establish methodologies and hypotheses for future studies of CI in Drosophila. We discuss the implications of the Two-by-One model towards functional mechanisms of CI, the emergence of incompatibility between Wolbachia strains, vector control applications, and CI gene nomenclature.
An introduction to the proceedings of the environmental release of engineered pests: Building an international governance framewor
5646Brown, Z. S., L. Carter and F. Gould, BMC Proceedings, 12:10. 2018-12-17 17:44:54.
In October 2016, a two-day meeting of 65 academic, government and industry professionals was held at North Carolina State University for early-stage discussions about the international governance of gene drives: potentially powerful new technologies that can be used for the control of pests, invasive species and disease vectors. Presenters at the meeting prepared seven manuscripts elaborating on the ideas raised. This BMC Proceedings issue presents the collection of these peer-reviewed manuscripts.
Towards inclusive social appraisal: risk, participation and democracy in governance of synthetic biology
5642Stirling, A., K. R. Hayes and J. Delborne, BMC Proceedings, 12:15. 2018-12-17 17:05:25.
Frameworks that govern the development and application of novel products, such as the products of synthetic biology, should involve all those who are interested or potentially affected by the products. The governance arrangements for novel products should also provide a democratic mechanism that allows affected parties to express their opinions on the direction that innovation does or does not take. In this paper we examine rationales, obstacles and opportunities for public participation in governance of novel synthetic biology products. Our analysis addresses issues such as uncertainties, the considering of alternative innovations, and broader social and environmental implications. The crucial issues in play go beyond safety alone, to include contending social values around diverse notions of benefit and harm. The paper highlights the need for more inclusive social appraisal mechanisms to inform governance of Synthetic Biology and alternative products, and discusses a few practical methods to help achieve this goal.
Public engagement pathways for emerging GM insect technologies
5640Burgess, M. M., J. D. Mumford and J. V. Lavery, BMC Proceedings, 12(Suppl 8):12. 2018-12-17 17:02:52.
Policy and management related to the release of organisms generated by emerging biotechnologies for pest management should be informed through public engagement. Regulatory decisions can be conceptually distinguished into the development of frameworks, the assessment of the release of a specific modified organism, and implementation decisions such as location and timing. Although these decisions are often intertwined in practice, the negotiation takes place at different stages of technology development and suggests different roles for public engagement. Some approaches to public engagement are more appropriate for different purposes and situations, and it is not always obvious how to go about matching the approach to the purpose. In addition to the diverse technologies involved in generating modified organisms, there are diverse publics with particular interests and different kinds of knowledge. Institutional interests range from commercial development to public regulation and future uptake. Contextual features, such as agency mandates, may limit or structure the extent and approach to public engagement. Different convening groups (government agencies, public interest groups, academics, businesses) and the kind of decision that is being considered determine what kind of input is needed and how the engaging groups will be constituted. This paper considers how the context of the release of genetically modified insects for pest control requires expanding approaches to the design of the public engagement.
GM insect pests under the Brazilian regulatory framework: development and perspectives
5638Andrade, P. P., M. A. da Silva Ferreira, M. S. Muniz and A. de Casto Lira-Neto, BMC Proceedings, 12:15. 2018-12-17 17:00:23.
The emergence of new technologies for genetic modification has broadened the range of possible new products. The regulations of many countries that could benefit from these new products may not be prepared to assess risks and enable science-based decision-making. This is especially acute in the case of genetically modified insects with potential use in public health and agriculture. Modifications of the regulatory framework, sometimes necessary to allow a proper risk assessment of products from new technologies, are strongly influenced by political decisions derived from the balance of power and interest among stakeholders. This article discusses the genesis of the Brazilian regulatory framework, its applicability for the risk assessment of genetically modified insects and the scenarios that have shaped the two biosafety laws that established the basis for the use of modern biotechnology in the country. It is concluded that, for the adoption of the new technologies, it is important to carefully navigate the political tensions by seeking the engagement and empowerment of stakeholders supporting science-based decision-making in order to gather the necessary support for adoption of risk assessment as the basis for final decisions, allowing the use of new technologies.
Regulation of emerging gene technologies in India
5636Ahuja, V., BMC Proceedings, 12:14. 2018-12-17 16:57:35.
In India, genetically modified organisms (GMOs) and the products thereof are regulated under the “Rules for the manufacture, use, import, export & storage of hazardous microorganisms, genetically engineered organisms or cells, 1989” (referred to as Rules, 1989) notified under the Environment (Protection) Act, 1986. These Rules are implemented by the Ministry of Environment, Forest and Climate Change, Department of Biotechnology and State Governments though six competent authorities. The Rules, 1989 are supported by series of guidelines on contained research, biologics, confined field trials, food safety assessment, environmental risk assessment etc.
Gene drive research: Why it matters
The Royal Society, Royal Society Statement, 2018-11-18 19:59:59.Gene drives are systems that bias the inheritance of a particular DNA sequence. Many such systems occur naturally and scientists are now investigating the potential to develop new ones using synthetic biology techniques. Synthetic gene drives are being developed for a range of purposes that would benefit humanity, but it is not possible at this stage to know whether the benefits outweigh the risks. Further research will help to reduce uncertainties and characterise potential risks and benefits. It is important that any research that does proceed is appropriately governed and combined with public debate. The Royal Society therefore recommends that the UN Convention on Biological Diversity avoid the adoption of any position that would support an international moratorium on gene drive research, including experimental field trials.
Ecological effects on underdominance threshold drives for vector control
16267D. Khamis, C. El Mouden, K. Kura and M. B. Bonsall, Journal of Theoretical Biology, 456:1-15. 2018-11-07 16:39:27.
Here, ecological and epidemiological dynamics are coupled to a model of mosquito genetics to investigate theoretically the impact of different types of underdominance gene drive on disease prevalence. We model systems with two engineered alleles carried either on the same pair of chromosomes at the same locus or homozygously on different pairs at different loci, genetic lethality that affects both sexes or only females, and bi-sex or male-only releases.
Population Consequences of Releasing Sex-Reversed Fish: Applications and Concerns
11500C. Wederkind, Sex Control in Aquaculture, Chp 8:179-188. 2018-11-02 20:38:44.
Sex differentiation is generally more labile in gonochoristic fish than it is, for example, in birds and mammals. Environmentally induced sex reversal is, therefore, often possible, and creates genotype‐phenotype mismatches that can be useful in population management. Interestingly, sex chromosomes of fish are typically not significantly decayed (i.e., all types of offspring of sex‐reversed individuals may be viable, including YY and WW individuals that can then often be sex reversed again). Releasing sex‐reversed fish, or releasing untreated YY and WW offspring of sex‐reversed fish, into natural populations can, therefore, affect the sex ratio of the population in the following generations and, hence, affect population growth.
Sex Control in Aquaculture: Concept to Practice
11497H.P. Wang and Z.G. Shen, Sex Control in Aquaculture, 2018-11-02 20:26:50.
Understanding sex determining (SD) mechanisms and related concepts in a wide range of fish species is critical for sex control and large‐scale monosex production in aquaculture, in which monosex culture is superior to mixed‐sex culture. Establishment of phenotypic sex is triggered by SD factor(s), modulated by complex molecular networks, and influenced by environmental conditions, steroid hormones, and endocrine disrupting chemicals. Temperature‐dependent sex determination (TSD) presents in fish, and the feature has been applied to monosex production in several fish species, since many downstream aspects of TSD are shared with genotypic sex determination (GSD). Although SD genes have been identified in some fish, the complex molecular networks involved in sex differentiation remain unclear. Large‐scale monosex production could be achieved in the third generation with sex‐linked markers (SLMs), and in the fourth generation with no available SLMs in fish with a XY or ZW SD mode. There is a great potential for producing large‐scale breeding systems for females in much less time if gynogenesis and sex reversal of XX‐females are combined. In addition, atypical genotypes (YY and WW) have the potential to serve as a biological tools to control invasive species in natural waters. In this chapter, we briefly review the concepts and practices of sex control in fish and aquaculture, based on the achievements during the past two decades.
Yes we can! Exciting progress and prospects for controlling invasives on islands and beyond
7964D. Simberloff, B. Keitt, D. Will, N. Holmes, E. Pickett and P. Genovesi, Western North American Naturalist, 78:942-958. 2018-10-22 14:34:34.
Eradication and maintenance management of island invasive species have long histories, and incremental improvements of existing technologies plus occasional novel approaches have led to more challenging targets and increased success rates in certain categories. Many nonnative mammals have been eradicated from islands, as have several nonnative birds, insects, and plants. Hundreds of rat populations have been eliminated, with a success rate over 80%, and islands over 10,000 ha are now feasible targets. Mouse eradication has proven more challenging, but aerial broadcast of anticoagulant toxins has led to increased success. Carnivore eradication-especially of feral housecats and foxes-has been frequently attempted with a recent success rate over 90%. Eradication of herbivores-primarily goats, rabbits, wild boar, and boar/pig hybrids-has been attempted almost 200 times, with a success rate over 90%. Trends in mammal eradication include more frequent attempts and higher success rates on larger islands and inhabited islands, as well as attempts targeting multiple invasive species. Documented conservation gains from island mammal eradications are numerous. For insects, about two-thirds of some 50 island attempts have succeeded, and most targeted agricultural pests. No summary statistics exist on island plant eradications, but several small infestations have been eradicated. Several insect and plant island invaders have been maintained at low densities by biological control, and plants have been controlled short of eradication by herbicides, often combined with physical or mechanical means. Failures in both eradication and maintenance management on islands often result from insufficient long-term commitment of resources. Excitement and controversy abound over the prospect that new techniques relying on molecular genetic tools-especially RNA-guided gene drives-may permit eradication or maintenance management of nonnative invaders in situations that have previously appeared extremely difficult or infeasible. Island populations of invertebrates, small mammals, and some plants are particularly propitious targets.
Multiple loci of small effect confer wide variability in efficiency and resistance rate of CRISPR gene drive
11267J. Champer, Z. Wen, A. Luthra, R. Reeves, J. Chung, C. Liu, Y. L. Lee, J. Liu, E. Yang, P. W. Messer and A. G. Clark, bioRxiv, 447615. 2018-10-19 19:06:27.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. CRISPR homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Such alleles cannot be converted to drive alleles, which would halt the spread of a drive through a population. To investigate the effects of natural genetic variation on resistance formation, we developed a CRISPR homing gene drive in Drosophila melanogaster and crossed it into the genetically diverse Drosophila Genetic Reference Panel (DGRP) lines, measuring several performance parameters. Most strikingly, resistance allele formation post-fertilization in the early embryo ranged from 7% to 79% among lines and averaged 42±18%. We performed a Genome-Wide Association Study (GWAS) using our results in the DGRP lines and found that the resistance and conversion rates were polygenic, with several genetic polymorphisms showing relatively weak association. RNAi knockdown of several of these genes confirmed their effect, but their small effect sizes implies that their manipulation will yield only modest improvements to the efficacy of gene drives.
Invasion Success and Management Strategies for Social Vespula Wasps
13740P. J. Lester and J. R. Beggs, Annual Review of Entomology, 64:51-71. 2018-09-26 19:38:03.
Three species of Vespula have become invasive in Australia, Hawai'i, New Zealand, and North and South America and continue to spread. Economically, their main negative effect is associated with pollination and the apicultural industry. Climate change is likely to exacerbate their impacts in many regions. Although investigated extensively, no effective biological control agents have yet been found. Emerging technologies such as gene drives are under consideration.
A spatially discrete, integral projection model and its application to invasive carp
11503R. A. Erickson, E. A. Eager, P. M. Kocovsky, D. C. Glover, J. L. Kallis and K. R. Long, Ecological Modelling, 387:163-171. 2018-09-21 20:46:26.
Natural resource managers and ecologists often desire an understanding of spatial dynamics such as migration, dispersion, and meta-population dynamics. Network-node models can capture these salient features. Additionally, the state-variable used with many species may be appropriately modeled as a continuous variable (e.g., length) and management activities sometimes can only target individuals of certain sizes. Integral projection models (IPMs) can capture this life history characteristic and allow for the examination of size-specific management. We combined an IPM with a network-node model to capture both of these salient features. We then demonstrated how this model could be used to understand and manage populations of invasive species focusing on grass carp as an example. Grass carp disrupt ecosystems outside of their native range and have spread around much of the world, including North America. The impacts of grass carp include adversely changing aquatic plant communities, which in turn affect a wide range of endpoints ranging from water quality to waterfowl recruitment. We specifically examined two theoretical systems using parameters from the literature. First, we modeled a lake with two tributaries and examined how modified sterile males could be used as a control tool. We found that modified sterile males may be a feasible control tool to limit population growth. Second, we modeled a series of river pools and examined how harvest and deterrents could be used to decrease the risk of expanding grass carp's range within a river system. Within this system, we also compared the impacts of size specific harvest and uniform harvest across all sizes. We found that targeting the largest, spawning populations may be more important than targeting the populations close to the invasion front for reducing the risk of spreading grass carp. We also demonstrate that size of harvested fish was important for controlling populations.
Pest demography critically determines the viability of synthetic gene drives for population control
11505K. E. Wilkins, T. A. A. Prowse, P. Cassey, P. Q. Thomas and J. V. Ross, Mathematical Biosciences, 305:160-169. 2018-09-13 20:48:39.
Synthetic gene drives offer a novel solution for the control of invasive alien species. CRISPR-based gene drives can positively bias their own inheritance, and comprise a DNA sequence that is replicated by homologous recombination. Since gene drives can be positioned to silence fertility or developmental genes, they could be used for population suppression. However, the production of resistant alleles following self-replication errors threatens the technology's viability for pest eradication in real-world applications. Further, a robust assessment of how pest demography impacts the expected progression of gene drives through populations is currently lacking. We used a deterministic, two-sex, birth-death model to investigate how demographic assumptions affect the efficiency of suppression drives for controlling invasive rodents on islands, for two different gene-drive strategies. We show that mass-action reproduction results in overly optimistic eradication outcomes when compared to the more realistic assumption of polygynous breeding. When polygyny was assumed, both gene-strategies failed due to the evolution of resistance unless a reproductive Allee effect (reduced reproductive rates at low population density) was also included; although model outcomes were highly sensitive to the strength of this effect. Increasing the size of the initial gene-drive introduction (up to 10% of carrying capacity) had little impact on population outcomes. Understanding the demography of a population targeted for eradication is critical before the viability of gene-drive suppression can be adequately assessed.
A sustainable synthetic biology approach for the control of the invasive golden mussel (Limnoperna fortunei)
19204M. F. Rebelo, L. F. Afonso, J. A. Americo, L. da Silva, J. L. B. Neto, F. Dondero and Q. Zhang, PeerJ Preprints, 6:e27164v3. 2018-09-12 14:52:07.
The recent development of the CRISPR-Cas9-based gene drive has created the conditions to seriously consider this technology to solve one of the major environmental challenges in biodiversity conservation i.e. the control of invasive species. There is no efficient control method for golden mussel infestation available so far. Here we discuss the technical and economic feasibility of using a synthetic biology based approach to fight and control the invasive mussel Limnoperna fortunei in South American rivers and reservoirs.
Sex determination in Neotropical fish: Implications ranging from aquaculture technology to ecological assessment
11495J. I. Fernandino and R. S. Hattori, General and Comparative Endocrinology, 273:172-183. 2018-07-07 20:24:06.
The high biodiversity of fish in the Neotropical region contrasts with scarce or biased studies on the mechanisms involved in the sex determination in members of this fauna. In this review, we attempted to compile the information available on determination, differentiation, and manipulation of sex for Neotropical species, with special focus on silversides and other two speciose groups, known as characins (Characiformes) and catfishes (Siluriformes). Currently, there is plenty of information available on chromosomal sex determination systems, which includes both male and female heterogamety with many variations, and sex chromosomes evolution at the macro chromosomal level. However, there is hitherto a blank in information at micro, gene/molecule levels and in research related to the effects of environmental cues on sex determination; most of reported studies are limited to silversides and guppies. In view of such a high diversity, it is critically necessary to establish key model species for relevant Neotropical fish taxa and also multi-disciplinary research groups in order to uncover the main patterns and trends that dictate the mechanisms of sex determination and gonadal differentiation in this icthyofauna. By increasing our knowledge on sex determination/differentiation with the identification of sex chromosome-linked markers or sex-determining genes, characterization of the onset timing of morphological gonadal differentiation, and determination of the environmental-hormonal labile period of gonadal sex determination in reference species, it will be possible to use those information as guidelines for application in other related groups. Overall, the strategic advance in this research field will be crucial for the development of biotechnological tools for aquaculture industry and for conservation of fish fauna from the Neotropical Region.
Global report on insecticide resistance in malaria vectors: 2010-2016.
12683WHO, World Health Organization, 2018-05-01 18:13:11.
Insecticide-based vector control is a cornerstone in the fight against malaria. Selection of vector-control interventions should take into account the resistance status of local mosquito vectors along with other factors associated with intervention deployment and use such as availability, cost and cost -effectiveness as well as population acceptance or compliance. Strategic insecticide resistance monitoring is therefore essential to inform evidence-based vector control.
Genetics-based methods for agricultural insect pest management
18687N. Alphey and M. B. Bonsall, Agricultural and Forest Entomology, 20:131-140. 2018-05-01 13:30:37.
Abstract The sterile insect technique is an area-wide pest control method that reduces agricultural pest populations by releasing mass-reared sterile insects, which then compete for mates with wild insects. Contemporary genetics-based technologies use insects that are homozygous for a repressible dominant lethal genetic construct rather than being sterilized by irradiation. Engineered strains of agricultural pest species, including moths such as the diamondback moth Plutella xylostella and fruit flies such as the Mediterranean fruit fly Ceratitis capitata, have been developed with lethality that only operates on females. Transgenic crops expressing insecticidal toxins are widely used; the economic benefits of these crops would be lost if toxin resistance spread through the pest population. The primary resistance management method is a high-dose/refuge strategy, requiring toxin-free crops as refuges near the insecticidal crops, as well as toxin doses sufficiently high to kill wild-type insects and insects heterozygous for a resistance allele. Mass-release of toxin-sensitive engineered males (carrying female-lethal genes), as well as suppressing populations, could substantially delay or reverse the spread of resistance. These transgenic insect technologies could form an effective resistance management strategy. We outline some policy considerations for taking genetic insect control systems through to field implementation.
One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogaster
5926Shropshire, J. D., J. On, E. M. Layton, H. Zhou and S. R. Bordenstein, Proceedings of the National Academy of Sciences, 115:4987. 2018-04-23 16:58:30.
The World Health Organization recommended pilot deployment of Wolbachia-infected mosquitoes to curb viral transmission to humans. Releases of mosquitoes are underway worldwide because Wolbachia can block replication of these pathogenic viruses and deterministically spread by a drive system termed cytoplasmic incompatibility (CI). Despite extensive research, the underlying genetic basis of CI remains only half-solved. We recently reported that two prophage WO genes recapitulate the modification component of CI in a released strain for vector control. Here we show that one of these genes underpins rescue of CI. Together, our results reveal the complete genetic basis of this selfish trait and pave the way for future studies exploring WO prophage genes as adjuncts or alternatives to current control efforts.Wolbachia are maternally inherited, intracellular bacteria at the forefront of vector control efforts to curb arbovirus transmission. In international field trials, the cytoplasmic incompatibility (CI) drive system of wMel Wolbachia is deployed to replace target vector populations, whereby a Wolbachia-induced modification of the sperm genome kills embryos. However, Wolbachia in the embryo rescue the sperm genome impairment, and therefore CI results in a strong fitness advantage for infected females that transmit the bacteria to offspring. The two genes responsible for the wMel-induced sperm modification of CI, cifA and cifB, were recently identified in the eukaryotic association module of prophage WO, but the genetic basis of rescue is unresolved. Here we use transgenic and cytological approaches to demonstrate that maternal cifA expression independently rescues CI and nullifies embryonic death caused by wMel Wolbachia in Drosophila melanogaster. Discovery of cifA as the rescue gene and previously one of two CI induction genes establishes a “Two-by-One” model that underpins the genetic basis of CI. Results highlight the central role of prophage WO in shaping Wolbachia phenotypes that are significant to arthropod evolution and vector control.
The ethical implications of population suppression and the irreversibility of gene drives
14167J. Kim, International Journal of Life Sciences Research, 2018-04-01 14:11:25.
This paper aims to examine the current situation by presenting important ethical arguments that include Chardin’s principle of irreversibility and Weiss’ beliefs on intergenerational equity, ideals upheld by the United Nations
Transgenic Mosquitoes – Fact or Fiction?
5907Wilke, A. B. B., J. C. Beier and G. Benelli, Trends in Parasitology, 34:456-465. 2018-03-08 16:14:34.
echnologies for controlling mosquito vectors based on genetic manipulation and the release of genetically modified mosquitoes (GMMs) are gaining ground. However, concrete epidemiological evidence of their effectiveness, sustainability, and impact on the environment and nontarget species is lacking; no reliable ecological evidence on the potential interactions among GMMs, target populations, and other mosquito species populations exists; and no GMM technology has yet been approved by the WHO Vector Control Advisory Group. Our opinion is that, although GMMs may be considered a promising control tool, more studies are needed to assess their true effectiveness, risks, and benefits. Overall, several lines of evidence must be provided before GMM-based control strategies can be used under the integrated vector management framework.
Population modification of Anopheline species to control malaria transmission
6694R. Carballar-Lejarazú and A. A. James, Pathogens and Global Health, 111:424-435. 2018-02-01 17:58:10.
Vector control strategies based on population modification of Anopheline mosquitoes may have a significant role in the malaria eradication agenda. They could consolidate elimination gains by providing barriers to the reintroduction of parasites and competent vectors, and allow resources to be allocated to new control sites while maintaining treated areas free of malaria. Synthetic biological approaches are being used to generate transgenic mosquitoes for population modification. Proofs-of-principle exist for mosquito transgenesis, the construction of anti-parasite effector genes and gene-drive systems for rapidly introgressing beneficial genes into wild populations. Key challenges now are to develop field-ready strains of mosquitoes that incorporate features that maximize safety and efficacy, and specify pathways from discovery to development. We propose three pathways and a framework for target product profiles that maximize safety and efficacy while meeting the demands of the complexity of malaria transmission, and the regulatory and social diversity of potential end-users and stakeholders.
