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.
Different mechanisms of X-ray irradiation-induced male and female sterility in Aedes aegypti
28570Zhang, H., Trueman, E., Hou, X. et al., BMC Biology, 21. 2023-11-29 14:14:21.
Aedes aegypti (Ae. aegypti) is the major vector that transmits many diseases including dengue, Zika, and filariasis in tropical and subtropical regions. Due to the growing resistance to chemical-based insecticides, biological control methods have become an emerging direction to control mosquito populations. The sterile insect technique (SIT) deploys high doses of ionizing radiation to sterilize male mosquitoes before the release. The Wolbachia-based population suppression method of the incompatible insect technique (IIT) involves the release of Wolbachia-infected males to sterilize uninfected field females. Due to the lack of perfect sex separation tools, a low percentage of female contamination is detected in the male population. To prevent the unintentional release of these Wolbachia-infected females which might result in population replacement, a low dose of X-ray irradiation is deployed to sterilize any female escapees. However, it remains unclear whether these irradiation-induced male and female sterilizations share common mechanisms.
Efficient sex separation by exploiting differential alternative splicing of a dominant marker in Aedes aegypti
28568Shih-Che Weng, Igor Antoshechkin, Eric Marois, Omar S. Akbari, PLoS Genetics, 2023-11-29 14:02:53.
Only female mosquitoes consume blood giving them the opportunity to transmit deadly human pathogens. Therefore, it is critical to remove females before conducting releases for genetic biocontrol interventions. Here we describe a robust sex-sorting approach termed SEPARATOR (Sexing Element Produced by Alternative RNA-splicing of A Transgenic Observable Reporter) that exploits sex-specific alternative splicing of an innocuous reporter to ensure exclusive dominant male-specific expression. Using SEPARATOR, we demonstrate reliable sex selection from early larval and pupal stages in Aedes aegypti, and use a Complex Object Parametric Analyzer and Sorter (COPAS) to demonstrate scalable high-throughput sex-selection of first instar larvae. Additionally, we use this approach to sequence the transcriptomes of early larval males and females and find several genes that are sex-specifically expressed. SEPARATOR can simplify mass production of males for release programs and is designed to be cross-species portable and should be instrumental for genetic biocontrol interventions.
Advances and challenges in synthetic biology for mosquito control
28545Shih-Che Weng, Reem A. Masri, Omar S. Akbari, Trends in Parasitology, 2023-11-28 11:40:23.
Mosquito-borne illnesses represent a significant global health peril, resulting in approximately one million fatalities annually. West Nile, dengue, Zika, and malaria are continuously expanding their global reach, driven by factors that escalate mosquito populations and pathogen transmission. Innovative control measures are imperative to combat these catastrophic ailments. Conventional approaches, such as eliminating breeding sites and using insecticides, have been helpful, but they face challenges such as insecticide resistance and environmental harm. Given the mounting severity of mosquito-borne diseases, there is promise in exploring innovative approaches using synthetic biology to bolster mosquitoes' resistance to pathogens, or even eliminate the mosquito vectors, as a means of control. This review outlines current strategies, future goals, and the importance of gene editing for global health defenses against mosquito-borne diseases.
Repeat mediated excision of gene drive elements for restoring wild-type populations
28543Pratima R Chennuri, Josef Zapletal, Raquel D Monfardini, Martial Loth Ndeffo-Mbah, Zach N Adelman, Kevin M Myles, bioRxiv, 2023-11-28 11:32:14.
We demonstrate here that single strand annealing (SSA) repair can be co-opted for the precise autocatalytic excision of a drive element. Although SSA is not the predominant form of DNA repair in eukaryotic organisms, we increased the likelihood of its use by engineering direct repeats at sites flanking the drive allele, and then introducing a double-strand DNA break (DSB) at a second endonuclease target site encoded within the drive allele. We have termed this technology Repeat Mediated Excision of a Drive Element (ReMEDE). Incorporation of ReMEDE into the previously described mutagenic chain reaction (MCR) gene drive, targeting the yellow gene of Drosophila melanogaster, replaced drive alleles with wild-type alleles demonstrating proof-of-principle. Although the ReMEDE system requires further research and development, the technology has a number of attractive features as a gene drive mitigation strategy, chief among these the potential to restore a wild-type population without releasing additional transgenic organisms or large-scale environmental engineering efforts.
Effects of different diets on Aedes aegypti adults: improving rearing techniques for sterile insect technique
28541Aynoanne Leandro Barbosa , Glayciane Costa Gois , Verenna Barros dos Santos , Aline Taiane de Macedo Pinto , Bianca Pires de Castro Andrade , Lucas Barbosa de Souza , Fernanda Hohana Almeida e Sá , Jair Fernandes Virginio and Mário Adriano Ávila Queiroz, Bulletin of Entomological Research, 2023-11-28 11:17:21.
The aim was to evaluate the effect of different energy diets available in adulthood on the longevity, dispersal capacity and sexual performance of Aedes aegypti produced under a mass-rearing system. To evaluate the effects of diets in relation to the survival of the adult male insects of Ae. aegypti, six treatments were used: sucrose at a concentration of 10%, as a positive control (sack10); starvation, as a negative control (starvation); sucrose at a concentration of 20% associated with 1 g/l of ascorbic acid (sac20vitC); wild honey in a concentration of 10% (honey10); demerara sugar in a 10% concentration (demerara10); and sucrose at a concentration of 20% associated with 1 g/l of ascorbic acid and 0.5 g/l of amino acid proline (sac20vitCPr). Each treatment had 16 cages containing 50 adult males. For the tests of flight ability and propensity to copulation, five treatments were used (saca10; sac20vitC; mel10; demerara10; and sac20vitCPr), with males each for flight ability and females copulated by a single male for copulation propensity. The diet composed of sucrose at a concentration of 20% associated with ascorbic acid, as an antioxidant, improved the survival, flight ability and propensity to copulate in Ae. aegypti males under mass-rearing conditions, and may be useful to enhance the performance of sterile males, thus improving the success of sterile insect technique programmes.
Utility of surveillance data for planning for dengue elimination in Yogyakarta, Indonesia: a scenario-tree modelling approach
28536Melanie Bannister-Tyrrell, Alison Hillman, Citra Indrian, Riris Andono Ahmad, Adi Utarini, Cameron P Simmons, Katherine L Anders, Evan Sergeant, BMJ Global Health, 8. 2023-11-28 10:54:45.
Field trials and modelling studies suggest that elimination of dengue transmission may be possible through widespread release of Aedes aegypti mosquitoes infected with the insect bacterium Wolbachia pipientis (wMel strain), in conjunction with routine dengue control activities. This study aimed to develop a modelling framework to guide planning for the potential elimination of locally acquired dengue in Yogyakarta, a city of almost 400 000 people in Java, Indonesia. A scenario-tree modelling approach was used to estimate the sensitivity of the dengue surveillance system (including routine hospital-based reporting and primary-care-based enhanced surveillance), and time required to demonstrate elimination of locally acquired dengue in Yogyakarta city, assuming the detected incidence of dengue decreases to zero in the future. Age and gender were included as risk factors for dengue, and detection nodes included the probability of seeking care, probability of sample collection and testing, diagnostic test sensitivity and probability of case notification. Parameter distributions were derived from health system data or estimated by expert opinion. Alternative simulations were defined based on changes to key parameter values, separately and in combination. For the default simulation, median surveillance system sensitivity was 0.131 (95% PI 0.111 to 0.152) per month. Median confidence in dengue elimination reached 80% after a minimum of 13 months of zero detected dengue cases and 90% confidence after 25 months, across different scenarios. The alternative simulations investigated produced relatively small changes in median system sensitivity and time to elimination. This study suggests that with a combination of hospital-based surveillance and enhanced clinic-based surveillance for dengue, an acceptable level of confidence (80% probability) in the elimination of locally acquired dengue can be reached within 2 years. Increasing the surveillance system sensitivity could shorten the time to first ascertainment of elimination of dengue and increase the level of confidence in elimination.
Gene drives for the extinction of wild metapopulations
28504Jason W. Olejarz, Martin A. Nowak, Journal of Theoretical Biology, 2023-11-27 10:57:31.
Population-suppressing gene drives may be capable of extinguishing wild populations, with proposed applications in conservation, agriculture, and public health. However, unintended and potentially disastrous consequences of release of drive-engineered individuals are extremely difficult to predict. We propose a model for the dynamics of a sex ratio-biasing drive, and using simulations, we show that failure of the suppression drive is often a natural outcome due to stochastic and spatial effects. We further demonstrate rock–paper–scissors dynamics among wild-type, drive-infected, and extinct populations that can persist for arbitrarily long times. Gene drive-mediated extinction of wild populations entails critical complications that lurk far beyond the reach of laboratory-based studies. Our findings help in addressing these challenges.
A toxin-antidote system contributes to interspecific reproductive isolation in rice
Shimin You, Zhigang Zhao, Xiaowen Yu, Shanshan Zhu, Jian Wang, Dekun Lei, Jiawu Zhou, Jing Li, Haiyuan Chen, Yanjia Xiao, Weiwei Chen, Qiming Wang, Jiayu Lu, Keyi Chen, Chunlei Zhou, Xin Zhang, Zhijun Cheng, Xiuping Guo, Yulong Ren, Xiaoming Zheng, Shijia, Nature Communications, 14. 2023-11-18 09:43:22.Breakdown of reproductive isolation facilitates flow of useful trait genes into crop plants from their wild relatives. Hybrid sterility, a major form of reproductive isolation exists between cultivated rice (Oryza sativa) and wild rice (O. meridionalis, Mer). Here, we report the cloning of qHMS1, a quantitative trait locus controlling hybrid male sterility between these two species. Like qHMS7, another locus we cloned previously, qHMS1 encodes a toxin-antidote system, but differs in the encoded proteins, their evolutionary origin, and action time point during pollen development. In plants heterozygous at qHMS1, ~ 50% of pollens carrying qHMS1-D (an allele from cultivated rice) are selectively killed. In plants heterozygous at both qHMS1 and qHMS7, ~ 75% pollens without co-presence of qHMS1-Mer and qHMS7-D are selectively killed, indicating that the antidotes function in a toxin-dependent manner. Our results indicate that different toxin-antidote systems provide stacked reproductive isolation for maintaining species identity and shed light on breakdown of hybrid male sterility.
Aedes aegypti microbiome composition covaries with the density of Wolbachia infection
28495Jane Pascar, Henry Middleton & Steve Dorus, Microbiome, 11. 2023-11-17 12:21:31.
Wolbachia is a widespread bacterial endosymbiont that can inhibit vector competency when stably transinfected into the mosquito, Aedes aegypti, a primary vector of the dengue virus (DENV) and other arboviruses. Although a complete mechanistic understanding of pathogen blocking is lacking, it is likely to involve host immunity induction and resource competition between Wolbachia and DENV, both of which may be impacted by microbiome composition. The potential impact of Wolbachia transinfection on host fitness is also of importance given the widespread release of mosquitos infected with the Drosophila melanogaster strain of Wolbachia (wMel) in wild populations. Here, population-level genomic data from Ae. aegypti was surveyed to establish the relationship between the density of wMel infection and the composition of the host microbiome.
Meiotic drive, postzygotic isolation, and the Snowball Effect
28418Robert L. Unckless, bioRxiv, 2023-11-14 12:43:39.
As populations diverge, they accumulate incompatibilities which reduce gene flow and facilitate the formation of new species. Simple models suggest that the genes that cause Dobzhansky-Muller incompatibilities should accumulate at least as fast as the square of the number of substitutions between taxa, the so-called snowball effect. We show, however, that in the special but possibly common case in which hybrid sterility is due primarily to cryptic meiotic (gametic) drive, the number of genes that cause postzygotic isolation may increase nearly linearly with the number of substitutions between species.
Transformative Novel Technologies and Global Environmental Governance
28377F. Rabitz, Cambridge University Press, 2023-11-13 09:55:21.
Transformative Novel Technologies are potential gamechangers for confronting climate change, biodiversity loss, and many other elements of the global environmental crisis, allowing us to achieve a more sustainable future. The contemporary and future international governance of these technologies has crucial implications for managing the global transition towards sustainability. This book is the first to present a comprehensive assessment of the impact of these technologies on international politics. The author examines the responses of international institutions to the emergence of these technologies, focusing on three broad domains: biotechnology, climate engineering, and mineral extraction in areas beyond national jurisdiction (the ocean floor or near-Earth asteroids). This book is aimed at a non-specialist, academic audience with interest in the international and environmental politics of sustainability and technology. This title is part of the Flip it Open Programme and may also be available Open Access. Check our website - Cambridge Core - for details.
The suppression of a selfish genetic element increases a male’s mating success in a fly
28422Sophie Lyth, Andrea J. Betancourt, Tom A. R. Price, Rudi L. Verspoor, Ecology and Evolution, 2023-11-12 13:33:47.
X chromosome meiotic drive (XCMD) kills Y-bearing sperm during spermatogenesis, leading to the biased transmission of the selfish X chromosome. Despite this strong transmission, some natural XCMD systems remain at low and stable frequencies, rather than rapidly spreading through populations. The reason may be that male carriers can have reduced fitness, as they lose half of their sperm, only produce daughters, and may carry deleterious alleles associated with XCMD. Thus, females may benefit from avoiding mating with male carriers, yielding a further reduction in fitness. Genetic suppressors of XCMD, which block the killing of Y sperm and restore fair Mendelian inheritance, are also common and could prevent the spread of XCMD. However, whether suppressed males are as fit as a wild-type male remains an open question, as the effect that genetic suppressors may have on a male's mating success is rarely considered. Here, we investigate the mating ability of XCMD males and suppressed XCMD males in comparison to wild-type males in the fruit fly Drosophila subobscura, where drive remains at a stable frequency of 20% in wild populations where it occurs. We use both competitive and non-competitive mating trials to evaluate male mating success in this system. We found no evidence that unsuppressed XCMD males were discriminated against. Remarkably, however, their suppressed XCMD counterparts had a higher male mating success compared to wild-type controls. Unsuppressed XCMD males suffered 12% lower offspring production in comparison to wild-type males. This cost appears too weak to counter the transmission advantage of XCMD, and thus the factors preventing the spread of XCMD remain unclear.
Gene Drive Mosquitoes from Islamic Perspective: A Preliminary Discussion
28385N. M. Isa, Global Journal Al-Thaqafah, 13. 2023-11-11 10:14:15.
Gene drive mosquitoes could spread desired trait, such as female infertility within a wild population at a rate higher than the normal inheritance rate and could eventually wipe out the population. Consequently, this makes gene drive mosquitoes one of the promising approaches in controlling mosquito-borne diseases, such as malaria and dengue. Despite its potentials, the development of gene drive mosquitoes has raised ethical concerns, mainly on the issues of safety and efficacy, as well as tampering with nature. Little research has been conducted to explore religious perspectives on this new advancement. This article aims to fill that gap by exploring the ethics of gene drive mosquitoes from Islamic perspectives. This article outlines three aspects, namely the purposes, the potential benefits and harms, and the need of the technology that should be considered when discussing whether gene drive mosquitoes should be allowed from Islamic perspectives. © (2023), (Universiti Sultan Azlan Shah). All Rights Reserved.
Generating and testing reagents for CRISPR/Cas9 based homologous recombination and gene drive in Tribolium
28363C. M. Hannah, J. H. Kennedy, M. Megan, E. Z. Gabriel, W. Michael and Z. Andrew, bioRxiv, 2023.11.07.566100. 2023-11-08 09:45:24.
CRISPR/Cas9 gene drive systems are possible in a few insects and ever expanding. Nonetheless, success in one species and techniques developed for it are not necessarily applicable to other species. As such, the development and expansion of gene drive systems is dependent upon direct experimentation. A critical aspect and potentially limiting factor of gene drive is the ability to induce Cas9-dependent homologous recombination. Here we report our attempts to induce Cas9-dependent homologous recombination and subsequent gene drive in Tribolium castaneum. Utilizing constructs containing one or two target gRNAs in combination with Cas9 under two different promoters and corresponding homology arms, we found a high incidence of CRISPR/Cas9 induced mutations but a complete lack of evidence of homologous recombination and genetic drive. Even though the generated constructs provide new resources for CRISPR/Cas9 modification of the Tribolium genome, our results suggest that Tribolium genome may be refractory towards Cas9-induced homologous recombination and additional modifications will be necessary to increase the potential for homologous recombination.Competing Interest StatementThe authors have declared no competing interest.
Symbiotic Wolbachia in mosquitoes and its role in reducing the transmission of mosquito-borne diseases: updates and prospects
28311A. Minwuyelet, G. P. Petronio, D. Yewhalaw, A. Sciarretta, I. Magnifico, D. Nicolosi, R. Di Marco and G. Atenafu, Frontiers in Microbiology, 14. 2023-11-08 08:20:47.
Mosquito-borne diseases such as malaria, dengue fever, West Nile virus, chikungunya, Zika fever, and filariasis have the greatest health and economic impact. These mosquito-borne diseases are a major cause of morbidity and mortality in tropical and sub-tropical areas. Due to the lack of effective vector containment strategies, the prevalence and severity of these diseases are increasing in endemic regions. Nowadays, mosquito infection by the endosymbiotic Wolbachia represents a promising new bio-control strategy. Wild-infected mosquitoes had been developing cytoplasmic incompatibility (CI), phenotypic alterations, and nutrition competition with pathogens. These reduce adult vector lifespan, interfere with reproduction, inhibit other pathogen growth in the vector, and increase insecticide susceptibility of the vector. Wild, uninfected mosquitoes can also establish stable infections through trans-infection and have the advantage of adaptability through pathogen defense, thereby selectively infecting uninfected mosquitoes and spreading to the entire population. This review aimed to evaluate the role of the Wolbachia symbiont with the mosquitoes (Aedes, Anopheles, and Culex) in reducing mosquito-borne diseases. Global databases such as PubMed, Web of Sciences, Scopus, and pro-Quest were accessed to search for potentially relevant articles. We used keywords: Wolbachia, Anopheles, Aedes, Culex, and mosquito were used alone or in combination during the literature search. Data were extracted from 56 articles’ texts, figures, and tables of the included article.
Male-killing virus in a noctuid moth Spodoptera litura
28367K. Nagamine, Y. Kanno, K. Sahara, T. Fujimoto, A. Yoshido, Y. Ishikawa, M. Terao, D. Kageyama and Y. Shintani, Proceedings of the National Academy of Sciences, 120:e2312124120. 2023-11-06 09:56:12.
A female-biased sex ratio is considered advantageous for the cytoplasmic elements that inhabit sexually reproducing organisms. There are numerous examples of bacterial symbionts in the arthropod cytoplasm that bias the host sex ratio toward females through various means, including feminization and male killing. Recently, maternally inherited RNA viruses belonging to the family Partitiviridae were found to cause male killing in moths and flies, but it was unknown whether male-killing viruses were restricted to Partitiviridae or could be found in other taxa. Here, we provide compelling evidence that a maternally inherited RNA virus, Spodoptera litura male-killing virus (SlMKV), selectively kills male embryos of the tobacco caterpillar Spodoptera litura, resulting in all-female broods. SlMKV injected into uninfected S. litura can also be inherited maternally and causes male killing. SlMKV has five genomic segments encoding seven open reading frames, has no homolog of known male-killing genes, and belongs to an unclassified group of arthropod-specific viruses closely related to Tolivirales. When transinfected into larvae, both male and female recipients allow SlMKV to proliferate, but only males die at the pupal stage. The viral RNA levels in embryonic and pupal male killing suggest that the mechanism of male killing involves the constitutive expression of viral products that are specifically lethal to males, rather than the male-specific expression of viral products. Our results, together with recent findings on male-killing partiti-like viruses, suggest that diverse viruses in arthropods tend to acquire male killing independently and that such viruses may be important components of intragenomic conflict in arthropods.
Current Status of the Main Olive Pests: Useful Integrated Pest Management Strategies and Genetic Tools
28380E. Lantero, B. Matallanas and C. Callejas, Applied Sciences, 13. 2023-11-06 09:55:38.
Mediterranean olive cultivation faces challenges in the global environmental change context. Pests and diseases caused by arthropods such as Bactrocera oleae, Prays oleae, and certain vectors of Xylella fastidiosa are expected to increase and spread in part due to this global scenario. The control of these arthropods has relied on synthetic pesticides, the misuse of which has led to pest population resistance and concerns about their negative impacts on biodiversity and global health. Integrated pest management (IPM) methods have emerged through the careful consideration of all available control techniques and the subsequent integration of appropriate measures that discourage the development of pest populations. This paper reviews the IPM guidelines for olive cultivation, prioritizing the use of biological control methods, and the integration of genetics and biotechnology, which bring precision, efficacy, and safety. It evidences the importance of genetic analysis in pest populations, pesticide resistance and in the contributions of predators to pest control. Advances in formulations and delivery systems for pesticides such as Bacillus thuringiensis, plant-incorporated protectants, improved SIT techniques, and the specific efficacy of biologicals pesticides are covered. Finally, this paper explores promising tools such as RNAi and gene drive while recognizing the ethical, environmental, and regulatory challenges associated with their use. Shortly, these innovations have the potential to reduce the environmental impacts of pests while ensuring the long-term viability of the olive industry.
Genetic conflict and the origin of multigene families: implications for sex chromosome evolution
28322E. Martí and A. M. Larracuente, Proceedings of the Royal Society B: Biological Sciences, 290:20231823. 2023-11-01 10:52:27.
Sex chromosomes are havens for intragenomic conflicts. The absence of recombination between sex chromosomes creates the opportunity for the evolution of segregation distorters: selfish genetic elements that hijack different aspects of an individual's reproduction to increase their own transmission. Biased (non-Mendelian) segregation, however, often occurs at a detriment to their host's fitness, and therefore can trigger evolutionary arms races that can have major consequences for genome structure and regulation, gametogenesis, reproductive strategies and even speciation. Here, we review an emerging feature from comparative genomic and sex chromosome evolution studies suggesting that meiotic drive is pervasive: the recurrent evolution of paralogous sex-linked gene families. Sex chromosomes of several species independently acquire and co-amplify rapidly evolving gene families with spermatogenesis-related functions, consistent with a history of intragenomic conflict over transmission. We discuss Y chromosome features that might contribute to the tempo and mode of evolution of X/Y co-amplified gene families, as well as their implications for the evolution of complexity in the genome. Finally, we propose a framework that explores the conditions that might allow for recurrent bouts of fixation of drivers and suppressors, in a dosage-sensitive fashion, and therefore the co-amplification of multigene families on sex chromosomes.
Biotechnological Potential of Microorganisms for Mosquito Population Control and Reduction in Vector Competence
28272R. D. Katak, A. M. Cintra, B. C. Burini, O. Marinotti, J. A. Souza-Neto and E. M. Rocha, Insects, 14. 2023-10-30 07:59:35.
Mosquitoes transmit pathogens that cause human diseases such as malaria, dengue fever, chikungunya, yellow fever, Zika fever, and filariasis. Biotechnological approaches using microorganisms have a significant potential to control mosquito populations and reduce their vector competence, making them alternatives to synthetic insecticides. Ongoing research has identified many microorganisms that can be used effectively to control mosquito populations and disease transmission. However, the successful implementation of these newly proposed approaches requires a thorough understanding of the multipronged microorganism-mosquito-;pathogen-environment interactions. Although much has been achieved in discovering new entomopathogenic microorganisms, antipathogen compounds, and their mechanisms of action, only a few have been turned into viable products for mosquito control. There is a discrepancy between the number of microorganisms with the potential for the development of new insecticides and/or antipathogen products and the actual available products, highlighting the need for investments in the intersection of basic research and biotechnology.
Conceptual risk assessment of mosquito population modification gene-drive systems to control malaria transmission: preliminary hazards list workshops
28220A. Kormos, G. Dimopoulos, E. Bier, G. C. Lanzaro, J. M. Marshall and A. A. James, Frontiers in Bioengineering and Biotechnology, 11. 2023-10-26 14:54:57.
The field-testing and eventual adoption of genetically-engineered mosquitoes (GEMs) to control vector-borne pathogen transmission will require them meeting safety criteria specified by regulatory authorities in regions where the technology is being considered for use and other locales that might be impacted. Preliminary risk considerations by researchers and developers may be useful for planning the baseline data collection and field research used to address the anticipated safety concerns. Part of this process is to identify potential hazards (defined as the inherent ability of an entity to cause harm) and their harms, and then chart the pathways to harm and evaluate their probability as part of a risk assessment. The University of California Malaria Initiative (UCMI) participated in a series of workshops held to identify potential hazards specific to mosquito population modification strains carrying gene-drive systems coupled to anti-parasite effector genes and their use in a hypothetical island field trial. The hazards identified were placed within the broader context of previous efforts discussed in the scientific literature. Five risk areas were considered i) pathogens, infections and diseases, and the impacts of GEMs on human and animal health, ii) invasiveness and persistence of GEMs, and interactions of GEMs with target organisms, iii) interactions of GEMs with non-target organisms including horizontal gene transfer, iv) impacts of techniques used for the management of GEMs and v) evolutionary and stability considerations. A preliminary hazards list (PHL) was developed and is made available here. This PHL is useful for internal project risk evaluation and is available to regulators at prospective field sites. UCMI project scientists affirm that the subsequent processes associated with the comprehensive risk assessment for the application of this technology should be driven by the stakeholders at the proposed field site and areas that could be affected by this intervention strategy.
Wolbachia endosymbionts manipulate the self-renewal and differentiation of germline stem cells to reinforce fertility of their fruit fly host
28215S. L. Russell, J. R. Castillo and W. T. Sullivan, PLOS Biology, 21:e3002335. 2023-10-24 14:41:16.
The alphaproteobacterium Wolbachia pipientis infects arthropod and nematode species worldwide, making it a key target for host biological control. Wolbachia-driven host reproductive manipulations, such as cytoplasmic incompatibility (CI), are credited for catapulting these intracellular bacteria to high frequencies in host populations. Positive, perhaps mutualistic, reproductive manipulations also increase infection frequencies, but are not well understood. Here, we identify molecular and cellular mechanisms by which Wolbachia influences the molecularly distinct processes of germline stem cell (GSC) self-renewal and differentiation. We demonstrate that wMel infection rescues the fertility of flies lacking the translational regulator mei-P26and is sufficient to sustain infertile homozygous mei-P26knockdown stocks indefinitely. Cytology revealed that wMel mitigates the impact of mei-P26 loss through restoring proper pMad, Bam, Sxl, and Orb expression. In Oregon R files with wild-type fertility, wMel infection elevates lifetime egg hatch rates. Exploring these phenotypes through dual-RNAseq quantification of eukaryotic and bacterial transcripts revealed that wMel infection rescues and offsets many gene expression changes induced by meiP26loss at the mRNA level. Overall, we show that wMel infection beneficially reinforces host fertility at mRNA, protein, and phenotypic levels, and these mechanisms may promote the emergence of mutualism and the breakdown of host reproductive manipulations.
General science-technology orientation, specific benefit–risk assessment frame, and public acceptance of gene drive biotechnology
28225X. Liu, C. L. Goldsmith, K. E. Kang, A. Vedlitz, Z. N. Adelman, L. W. Buchman, E. Heitman and R. F. Medina, Risk Analysis, 2023-10-23 15:04:31.
Abstract With limited understanding of most new biotechnologies, how do citizens form their opinion and what factors influence their attitudes about these innovations? In this study, we use gene drive biotechnology in agricultural pest management as an example and theoretically propose that given low levels of knowledge and awareness, citizens? acceptance of, or opposition to, gene drive is significantly shaped by two predisposition factors: individuals? general orientation toward science and technology, and their specific benefit-risk assessment frame. Empirically, we employ data collected from a recent US nationally representative public opinion survey (N = 1220) and conduct statistical analyses to test the hypotheses derived from our theoretical expectations. Our statistical analyses, based on various model specifications and controlling for individual-level covariates and state-fixed effects, show that citizens with a more favorable general orientation toward science and technology are more likely to accept gene drive. Our data analyses also demonstrate that citizens? specific gene drive assessment frame?consisting of a potential benefit dimension and a potential risk dimension, significantly shapes their attitudes as well?specifically, people emphasizing more on the benefit dimension are more likely to accept gene drive, whereas those who place more importance on the risk dimension tend to oppose it. We discuss contributions of our study and make suggestions for future research in the conclusion.
Incorporating ecology into gene drive modelling
28150J. Kim, K. D. Harris, I. K. Kim, S. Shemesh, P. W. Messer and G. Greenbaum, Ecology Letters, 26:S62-S80. 2023-10-23 11:37:54.
Abstract Gene drive technology, in which fast-spreading engineered drive alleles are introduced into wild populations, represents a promising new tool in the fight against vector-borne diseases, agricultural pests and invasive species. Due to the risks involved, gene drives have so far only been tested in laboratory settings while their population-level behaviour is mainly studied using mathematical and computational models. The spread of a gene drive is a rapid evolutionary process that occurs over timescales similar to many ecological processes. This can potentially generate strong eco-evolutionary feedback that could profoundly affect the dynamics and outcome of a gene drive release. We, therefore, argue for the importance of incorporating ecological features into gene drive models. We describe the key ecological features that could affect gene drive behaviour, such as population structure, life-history, environmental variation and mode of selection. We review previous gene drive modelling efforts and identify areas where further research is needed. As gene drive technology approaches the level of field experimentation, it is crucial to evaluate gene drive dynamics, potential outcomes, and risks realistically by including ecological processes.
Benefits and risks of gene drives for invasive plant management – the case for common tansy
28162L. Croghan, A. G. Smith, M. A. Tancos, N. O. Anderson and R. L. Becker, Frontiers in Agronomy, 5. 2023-10-20 12:05:59.
Invasive plants cause significant environmental and economic damage, but land managers have few control options. Common tansy (Tanacetum vulgare) is prevalent in many US states and is one of the most reported invasive plants in Minnesota. Controlling common tansy poses a challenge due to its extensive distribution and association with diverse plant communities. A gene drive is being explored as a genetic biocontrol method for the management of several non-native invasives, including common tansy in North America. Gene drives have emerged as a novel biotechnology application with potential to improve public health, promote conservation, and increase agricultural productivity. In common tansy, gene drives could be developed to target genes that would reduce or eliminate female fertility and consequently inhibit common tansy seed production. Using common tansy as an example, we outline risks associated with the use of gene drive technology for invasive plant control and explain how risks may be mitigated. Understanding potential benefits and risks associated with gene drives in the early stages of development is crucial. Mitigating risks, receiving stakeholder input, and navigating the regulatory environment will play an important role in gene drive development and deployment.
Gene drive in plants emerges from infancy
28152M. J. A. Awan, R. Z. Naqvi, I. Amin and S. Mansoor, Trends in Plant Science, 2023-10-18 11:43:35.
Selfish genetic elements (SGEs) display biased transmission to offspring. However, their breeding potential has remained obscure. Wang et al. recently reported a natural gene-drive system that can be harnessed to prevent hybrid incompatibility and to develop a synthetic gene-drive (SGD) system for crop improvement.
X-rays are as effective as gamma-rays for the sterilization of Glossina palpalis gambiensis Vanderplank, 1911 (Diptera: Glossinidae) for use in the sterile insect technique
28223B. A. Kaboré, A. Nawaj, H. Maiga, O. Soukia, S. Pagabeleguem, M. S. G. Ouédraogo/Sanon, M. J. B. Vreysen, R. L. Mach and C. J. de Beer, Scientific Reports, 13:17633. 2023-10-17 15:00:27.
An area-wide integrated pest management strategy with a sterile insect technique (SIT) component requires a radiation source for the sterilisation of male insects. Self-contained gamma irradiators, which were exclusively used in past SIT programmes, are now facing increasing constraints and challenges due to stringent regulations. As a potential alternative, new generation high output X-ray irradiators have been proposed. The feasibility of using X-ray irradiators was assessed by comparing the effects of both gamma- and X-ray irradiators on biological parameters of Glossina palpalis gambiensis (Vanderplank, 1911), that are important for SIT applications. The gamma irradiator Foss Model 812 and two X-ray irradiators, the Rad Source 2400 and the blood irradiator Raycell Mk2 were used. Glossina palpalis gambiensis males were exposed to radiation as pupae. A radiation dose of 110 Gy or above induced more than 97% sterility in females that mated with the irradiated males for all the irradiators. Adult emergence rate, flight propensity, survival and mating performance did not differ between gamma- and X-rays irradiators. These results suggest that irradiating pupae with a dose of 110 Gy is optimal for both gamma-and X-ray irradiators used in this study, to achieve a sterility of approximately 99%. Similar research on other tsetse species could gradually phase out the use of gamma-ray irradiators in favour of X-rays irradiators, especially for smaller SIT programmes.
Cleave and Rescue gamete killers create conditions for gene drive in plants
28140O. Georg, L. J. Michelle, I. Tobin and A. H. Bruce, bioRxiv, 2023.10.13.562303. 2023-10-14 10:23:38.
Gene drive elements promote the spread of linked traits, even when their presence confers a fitness cost to carriers, and can be used to change the composition or fate of wild populations. Cleave and Rescue (ClvR) drive elements sit at a fixed chromosomal position and include a DNA sequence-modifying enzyme such as Cas9/gRNAs (the Cleaver/Toxin) that disrupts endogenous versions of an essential gene, and a recoded version of the essential gene resistant to cleavage (the Rescue/Antidote). ClvR spreads by creating conditions in which those lacking ClvR die because they lack functional versions of the essential gene. We demonstrate the essential features of ClvR gene drive in the plant Arabidopsis thaliana through killing of gametes that fail to inherit a ClvR that targets the essential gene YKT61, whose expression is required in male and female gametes for their survival. Resistant (uncleavable but functional) alleles, which can slow or prevent drive, were not observed. Modeling shows plant ClvRs can be used to rapidly drive population modification or suppression. Possible applications in weed control, plant breeding and conservation are discussed.Competing Interest StatementThe authors have filed patent applications on ClvR and related technologies (U.S. Application No. 15/970,728 and No. 16/673,823).
Wolbachia enhances the survival ofDrosophila infected with fungal pathogens
28218J. Perlmutter, I., A. Atadurdyyeva, M. Schedl, E. and R. Unckless, L., bioRxiv, 2023.09.30.560320. 2023-10-11 14:49:32.
Wolbachia bacteria of arthropods are at the forefront of basic and translational research on multipartite host-symbiont-pathogen interactions. These microbes are vertically inherited from mother to offspring via the cytoplasm. They are the most widespread endosymbionts on the planet due to their infamous ability to manipulate the reproduction of their hosts to spread themselves in a population, and to provide a variety of fitness benefits to their hosts. Importantly, some strains of Wolbachia can inhibit viral pathogenesis within and between arthropod hosts. Mosquitoes carrying the wMel Wolbachia strain of Drosophila melanogaster have a greatly reduced capacity to spread viruses like dengue and Zika to humans. Therefore, Wolbachia are the basis of several global vector control initiatives. While significant research efforts have focused on viruses, relatively little attention has been given to Wolbachia-fungal interactions despite the ubiquity of fungal entomopathogens in nature. Here, we demonstrate that Wolbachia increase the longevity of their Drosophila melanogaster hosts when challenged with a spectrum of yeast and filamentous fungal pathogens. We find that this pattern can vary based on host genotype, sex, and fungal species. Further, Wolbachia correlates with higher fertility and reduced pathogen titers during initial fungal infection, indicating a significant fitness benefit. This study demonstrates Wolbachia’s role in diverse fungal pathogen interactions and determines that the phenotype is broad, but with several variables that influence both the presence and strength of the phenotype. These results enhance our knowledge of the strategies Wolbachia uses that likely contribute to such a high global symbiont prevalence.Importance Wolbachia bacteria of arthropods are at the forefront of global initiatives to fight arthropod-borne viruses. Despite great success in using the symbiont to fight viruses, little research has focused on Wolbachia-fungal interactions. Here, we find that Wolbachia of Drosophila melanogaster, the same strain widely used in antiviral initiatives, can also increase the longevity of flies systemically infected with a panel of yeast and filamentous fungal pathogens. The symbiont also partially increases host fertility and reduces fungal titers during early infection, indicating a significant fitness benefit. This represents a major step forward in Wolbachia research since its pathogen blocking abilities can now be extended to a broad diversity of another major branch of microbial life. This discovery may inform basic research on pathogen blocking and has potential translational applications in areas including biocontrol in agriculture.Competing Interest StatementThe authors have declared no competing interest.
Overriding Mendelian inheritance in Arabidopsis with a CRISPR toxin-antidote gene drive that impairs pollen germination
28101L. Yang, J. Bingke, C. Jackson and Q. Wenfeng, bioRxiv, 2023.10.10.561637. 2023-10-11 07:52:15.
Synthetic gene drives, inspired by natural selfish genetic elements, present transformative potential for disseminating traits that benefit humans throughout wild populations, irrespective of potential fitness costs. Here, we constructed a gene drive system called CRISPR-Assisted Inheritance utilizing NPG1 (CAIN), which employs a toxin-antidote mechanism in the male germline to override Mendelian inheritance in plants. Specifically, a gRNA-Cas9 cassette targets the essential No Pollen Germination 1 (NPG1) gene, serving as the toxin to block pollen germination. A recoded, CRISPR-resistant copy of NPG1 serves as the antidote, providing rescue only in pollen cells that carry the drive. To limit potential consequences of inadvertent release, we used self-pollinating Arabidopsis thaliana as a model. The drive demonstrated a robust 88-99% transmission rate over two successive generations, producing minimal resistance alleles that are unlikely to inhibit drive spread. Our study provides a strong basis for rapid genetic modification or suppression of outcrossing plant populations.Competing Interest StatementThe authors have declared no competing interest.
Wolbachia interferes with Zika virus replication by hijacking cholesterol metabolism in mosquito cells
28094B. Edwards, E. A.-O. X. Ghedin and D. A.-O. Voronin, Microbiology Spectrum, 2023-10-09 07:37:16.
Zika virus is a member of the arbovirus Flaviviridae family transmitted by Aedes mosquitos and it is associated with microcephaly in infants born to infected mothers. Wolbachia is an intracellular gram-negative alpha-proteobacteria that infects many species of arthropods, including mosquitos. The presence of Wolbachia in mosquitos has been shown to control the vector population and suppress arbovirus transmission. One mechanism of Wolbachia-mediated interference with virus replication is competition over host resources between Wolbachia and the virus. We hypothesize that cholesterol metabolism is involved in Wolbachia-mediated virus suppression due to its important role in Zika virus replication. In this study, we determined that Wolbachia impacted virus replication by altering cholesterol biosynthesis in Aedes albopictus C6/36 cells, diverting resources from the host cell mevalonate (MVA) pathway to fulfill the needs of the bacteria. This resulted in a decrease of total cholesterol, increased Wolbachia loads, and decreased viral titers. Inhibition of the MVA pathway using fluvastatin decreased total cholesterol and viral titers, mimicking the effects of Wolbachia on the virus in Wolbachia-free cells. We also found that Wolbachia-infected cells had depleted lipid droplets, the main component of which is cholesterol esters. We confirmed that cholesterol esterases were upregulated in response to virus infection in C6/36 cells. Functional analysis showed that alteration of cholesterol metabolism simulated Wolbachia-mediated inhibition of virus infection in C6/36 cells. Our study provides a mechanism behind Wolbachia-induced interference of arbovirus replication and could help advance strategies to control arbovirus pathogens in insect vectors and human infections. IMPORTANCE Arthropod-borne viruses are emerging pathogens that are spread widely by mosquitos. Zika virus is an arbovirus that can infect humans and be transmitted from an infected mother to the fetus, potentially leading to microcephaly in infants. One promising strategy to prevent disease caused by arboviruses is to target the insect vector population. Recent field studies have shown that mosquito populations infected with Wolbachia bacteria suppress arbovirus replication and transmission. Here, we describe how intracellular bacteria redirect resources within their host cells and suppress Zika virus replication at the cellular level. Understanding the mechanism behind Wolbachia-induced interference of arbovirus replication could help advance strategies to control arbovirus pathogens in insect vectors and human populations. FAU - Edwards, Brent
Expansions to the MGDrivE suite for simulating the efficacy of novel gene-drive constructs in the control of mosquito-borne diseases
28003J. B. Bennett, S. L. Wu, P. R. Chennuri, K. M. Myles and M. L. Ndeffo-Mbah, BMC Research Notes, 16:258. 2023-10-05 08:39:23.
The MGDrivE (MGDrivE 1 and MGDrivE 2) modeling framework provides a flexible and expansive environment for testing the efficacy of novel gene-drive constructs for the control of mosquito-borne diseases. However, the existing model framework did not previously support several features necessary to simulate some types of intervention strategies. Namely, current MGDrivE versions do not permit modeling of small molecule inducible systems for controlling gene expression in gene drive designs or the inheritance patterns of self-eliminating gene drive mechanisms. Here, we demonstrate a new MGDrivE 2 module that permits the simulation of gene drive strategies incorporating small molecule-inducible systems and self-eliminating gene drive mechanisms. Additionally, we also implemented novel sparsity-aware sampling algorithms for improved computational efficiency in MGDrivE 2 and supplied an analysis and plotting function applicable to the outputs of MGDrivE 1 and MGDrivE 2.
Mosquito Embryo Microinjection
27969R. A. Harrell, Cold Spring Harbor Protocols, 2023-10-03 07:27:01.
Genetically modified (GM) mosquitoes are an important tool in the fight against mosquito-borne disease, both indirectly through their use in research investigating host–pathogen interaction, mosquito olfaction, and anthropomorphic behavior and in future direct uses for suppression and possibly eradication through sterile insect technique (SIT) and/or gene-drive programs. Successful creation of GM mosquitoes depends on microinjection procedures that precisely deliver injection materials while causing as little damage to mosquito embryos as possible. Genetic modification reagents, such as transposon system components (vector plasmids, helper plasmids, and helper mRNA), and CRISPR–Cas9 components (guide RNAs, Cas9 protein, plasmids expressing Cas9 and/or guide RNAs, and donor plasmids used in homology-directed repair [HDR]), must be delivered into the preblastoderm embryo at the posterior end where the pole cells will form before cellularization occurs. Sharp needles that pierce the embryo easily are important tools in this procedure and work best when the embryos are not desiccated. The two main procedures for mosquito embryo microinjection involve injecting embryos under halocarbon oil or under aqueous solution.
The double-edged sword effect of expanding Wolbachia deployment in dengue endemic settings
28137M. G. Pavan, G. A. Garcia, M. R. David and R. Maciel-de-Freitas, The Lancet Regional Health - Americas, 27:100610. 2023-10-02 10:16:37.
We can use Brazil as a showcase to foresee and avoid a double-edged sword effect associated with Wolbachia releases. Insecticide resistance of native Ae. aegypti populations is spread worldwide (http://aedes.irmapper.com), and positive results should boost Wolbachia deployment in other dengue endemic settings around the world. Aedes aegypti populations are heterogeneous and nationwide releases of a Wolbachia strain whose genetic backcross belong to a specific locality would produce an unsought homogenization of vector populations. Aedes aegypti homogenisation at large geographic scales could impose additional undesirable consequences in the long-term by promoting genetic hitchhiking of traits such as higher vector competence, lower susceptibility to repellents and insecticides, or more avid host-seeking and biting behaviour. Available data has shown that ensuring adherence to local characteristics, specially a matching genetic between native and released mosquitoes, is critical to enhance the likelihood of achieving a faster introgression in the field, realizing cost and time savings over the globe. Probably there are a myriad of yet undiscovered traits beyond insecticide resistance that may influence vector local adaptation and would affect the success of released strains. Therefore, neglecting the genetic diversity in favour of centralising the rearing of mosquitoes with Wolbachia for nationwide releases could represent a drawback for future releases. Long-term studies regarding the consequences of releasing mosquitoes with homogenous genotypes in diverse ecological and epidemiological scenarios remain a critical research priority, essential for informed decision-making and sustainable management of mosquito-borne diseases.
Wolbachia-mediated resistance to Zika virus infection in Aedes aegypti is dominated by diverse transcriptional regulation and weak evolutionary pressures
27974E. C. Boehm, A. S. Jaeger, H. J. Ries, D. Castañeda, A. M. Weiler, C. C. Valencia, J. Weger-Lucarelli, G. D. Ebel, S. L. O’Connor, T. C. Friedrich, M. Zamanian and M. T. Aliota, PLOS Neglected Tropical Diseases, 17:e0011674. 2023-10-02 07:38:35.
A promising candidate for arbovirus control and prevention relies on replacing arbovirus-susceptible Aedes aegypti populations with mosquitoes that have been colonized by the intracellular bacterium Wolbachia and thus have a reduced capacity to transmit arboviruses. This reduced capacity to transmit arboviruses is mediated through a phenomenon referred to as pathogen blocking. Pathogen blocking has primarily been proposed as a tool to control dengue virus (DENV) transmission, however it works against a range of viruses, including Zika virus (ZIKV). Despite years of research, the molecular mechanisms underlying pathogen blocking still need to be better understood. Here, we used RNA-seq to characterize mosquito gene transcription dynamics in Ae. aegypti infected with the wMel strain of Wolbachia that are being released by the World Mosquito Program in Medellín, Colombia. Comparative analyses using ZIKV-infected, uninfected tissues, and mosquitoes without Wolbachia revealed that the influence of wMel on mosquito gene transcription is multifactorial. Importantly, because Wolbachia limits, but does not completely prevent, replication of ZIKV and other viruses in coinfected mosquitoes, there is a possibility that these viruses could evolve resistance to pathogen blocking. Therefore, to understand the influence of Wolbachia on within-host ZIKV evolution, we characterized the genetic diversity of molecularly barcoded ZIKV virus populations replicating in Wolbachia-infected mosquitoes and found that within-host ZIKV evolution was subject to weak purifying selection and, unexpectedly, loose anatomical bottlenecks in the presence and absence of Wolbachia. Together, these findings suggest that there is no clear transcriptional profile associated with Wolbachia-mediated ZIKV restriction, and that there is no evidence for ZIKV escape from this restriction in our system.
Situating the social sciences in responsible innovation in the global south: the case of gene drive mosquitoes
28148K. Ledingham, C. Opesen, S. Hartley and S. Neema, Journal of Responsible Innovation, 10:2264100. 2023-10-01 11:32:46.
There has been growing attention in recent years on the potential reconfiguration of responsible innovation (RI) to increase its relevance for global challenges in the Global South. This reconfiguration will require a broad and empowered role for social scientists. Yet RI has been preoccupied with public and stakeholder inclusion, rather than social science inclusion. We probe this gap through a case study of the social sciences in the development of gene drive mosquitoes for malaria control in Mali and Uganda. Our data reveals potential diverse roles and future research agendas for the social sciences. We outline some challenges facing the social sciences in this space and ways to promote and support them. Lastly, we argue that RI?s predilection for reflexive and critical social science obscures a richer repertoire of social science roles that are an imperative and fundamental part of efforts to address global challenges in the Global South.
Next-generation genetic sexing strain establishment in the agricultural pest Ceratitis capitata
27972S. Davydova, J. Liu, N. Kandul, P., W. E. Braswell, O. Akbari, S. and A. Meccariello, bioRxiv, 2023.09.29.560088. 2023-10-01 07:32:11.
Tephritid fruit fly pests pose an increasing threat to the agricultural industry due to their global dispersion and a highly invasive nature. Here we showcase the feasibility of an early-detection SEPARATOR sex sorting approach through using the non-model Tephritid pest, Ceratitis capitata. This system relies on female-only fluorescent marker expression, accomplished through the use of a sex-specific intron of the highly-conserved transformer gene from C. capitata and Anastrepha ludens. The herein characterized strains have 100% desired phenotype outcomes, allowing accurate male-female separation during early development. Overall, we describe an antibiotic and temperature-independent sex-sorting system in C. capitata, which, moving forward, may be implemented in other non-model Tephritid pest species. This strategy can facilitate the establishment of genetic sexing systems with endogenous elements exclusively, which, on a wider scale, can improve pest population control strategies like sterile insect technique.Competing Interest StatementO.S.A is a founder of Agragene, Inc. and Synvect, Inc. with equity interest. N.P.K is a founder of Synvect, Inc. with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. All other authors declare no competing interests
Supergenes as drivers of ant evolution
27997M. Chapuisat, Myrmecological News, 33:1-18. 2023-09-30 08:25:16.
Ants show striking diversity in social organization, raising major questions on the proximate and ultimate causes of such variation. The shift from one-queen (= monogyne) societies to multi-queen (= polygyne) societies has long been viewed as a phenotypically plastic response to ecological and social conditions. In contrast to this view, in five independent ant lineages, alternative forms of colony social organization are controlled by supergenes. Supergenes are large groups of linked genes determining compound adaptive phenotypes, like colour morphs, ecotypes, or social forms. In the best-studied socially polymorphic ant species, Solenopsis invicta and Formica selysi, a supergene variant (= haplotype) is exclusively found in multi-queen colonies and does not recombine with the alternative haplotype. How did such supergenes spread? Supergenes might be favoured by natural selection because they link co-adapted alleles that are beneficial in one social form. The absence of recombination ensures that these alleles are transmitted together and prevents maladaptive combinations between alleles. However, supergenes can also spread selfishly, by distorting Mendelian transmission in their favour. Non-recombining regions are indeed prone to harbour selfish genetic elements, which are typically formed by tight linkage of a killer gene, or toxin, and a rescue gene, or antidote. Strikingly, the social supergene haplotypes associated with multi-queen colonies of ants selfishly favour their own transmission by causing gene drive through distinct mechanisms. In S. invicta, the “polygyne” haplotype causes a green-beard effect: Workers that carry this haplotype kill queens that lack it. In F. selysi, the “polygyne” haplotype is a maternal-effect killer: Offspring of mothers that carry this selfish haplotype fail to hatch when they do not inherit a copy of the haplotype. Overall, the ants’ social supergenes induce unexpected combinations of adaptive and detrimental effects across levels of biological organization. On the one hand, they coordinate individual and colony-level traits, such as queen number, mating system, and dispersal. On the other hand, supergenes cause selfish gene drive and lethal effects due to accumulation of deleterious mutations. The evolutionary dynamics of these large groups of linked genes is therefore particularly complex, and explaining their long-term maintenance is challenging. I argue that social supergenes can be drivers of ant evolution because they spread selfishly and show lethal effects. Therefore, an understanding of the unusual properties of the underlying genetic system is needed to explain variation in colony queen number.
Testing a candidate meiotic drive locus identified by pool sequencing
27983D. A. Barbash, B. Jin, K. H. C. Wei and A.-M. Dion-Côté, G3 Genes|Genomes|Genetics, 2023-09-28 07:56:24.
Meiotic drive biases the transmission of alleles in heterozygous individuals, such that Mendel’s law of equal segregation is violated. Most examples of meiotic drive have been discovered over the past century based on causing sex-ratio distortion or the biased transmission of easily scoreable genetic markers that were linked to drive alleles. More recently, several approaches have been developed that attempt to identify distortions of Mendelian segregation genome-wide. Here we test a candidate female meiotic drive locus in Drosophila melanogaster, identified previously as causing a ∼54:46 distortion ratio using sequencing of large pools of backcross progeny. We inserted fluorescent visible markers near the candidate locus and scored transmission in thousands of individual progeny. We observed a small but significant deviation from the Mendelian expectation, however it was in the opposite direction to that predicted based on the original experiments. We discuss several possible causes of the discrepancy between the two approaches, noting that subtle viability effects are particularly challenging to disentangle from potential small-effect meiotic drive loci. We conclude that pool sequencing approaches remain a powerful method to identify candidate meiotic drive loci, but that genotyping of individual progeny at early developmental stages may be required for robust confirmation.
A natural gene drive element confers speciation in rice
28000Y. Li, S. Liu and R. Shen, Chinese Science Bulletin, 68:3400-3402. 2023-09-27 08:30:59.
For a long time, although many important advances have been made in the field of rice hybrid sterility, the specific molecular mechanism behind the "killer-protector"/ "poison-antidote" model has been unclear. Recently, the team of Academician Wan Jianmin of Nanjing Agricultural University identified a major locus RHS12 controlling pollen sterility of indica-japonica hybrids. This site belongs to the same locus as the recently cloned pf12 and Se[16,17]. Genetic analysis revealed that RHS12 consists of two closely linked genes, iORF3/DUYAO and iORF4/JIEYAO. These two genes are commonly found in indica rice genome, but not in some japonica rice genomes. iORF3 (DUYAO) encodes a poison protein localized in mitochondria. DUYAO interacts with OsCOX11, a core functional protein in the mitochondrial respiratory chain, to cause mitochondrial dysfunction and induce programmed cell death (program cell death, PCD) leading to pollen abortion. iORF4 (JIEYAO) encodes an antidote protein that interacts with the DUYAO protein to bring DUYAO to the autophagosome for degradation, thereby releasing OsCOX11 for normal pollen development (Fig. 1). Therefore, during the pollen development of indica-japonica hybrids, the pollen of japonica type without this pair of genes was selectively aborted, while the pollen of indica type with this pair of genes developed normally. For the first time, this study completely and clearly clarified the mechanism of RHS12 regulating rice hybrid sterility from the genetic, cellular and molecular levels, and achieved a major breakthrough in this field.
Engineered and natural gene drives: mechanistically the same, yet not same in kind
27995R. F. Medina and J. Kuzma, Nature Communications, 14:5994. 2023-09-26 08:18:08.
We propose the use of the terms natural gene drive (NGD) and engineered gene drive (EGD) arguing against James et al.1, who think both should be included within the term “gene drive”, based on their mechanistic similarities. Thanks to CRISPR-Cas-based gene editing, engineered gene drive has suddenly become feasible as a potential cost-effective pest control tool that could help us resolve wicked challenges2,3 . In nature, several organisms harbor genes that “selfishly” drive themselves into populations. This natural gene drive uses similar mechanisms to the ones use today to drive engineered genes into laboratory populations4 article we disagree with James et al.1 .In this who have recently proposed that because natural and engineered gene drives are mechanistically indistinguishable from a molecular standpoint, they should both be referred as “gene drives” because “a gene drive is a gene drive.” We instead propose that two terms be used to distinguish between natural and engineered gene drives, we second Wells and Steinbrecher5 arguments, and propose to use the terms natural gene drive (NGD) and engineered gene drive (EGD).
Wolbachia Induces Structural Defects Harmful to Drosophila simulans Riverside Spermiogenesis.
28142M. G. Riparbelli, A. Pratelli and G. Callaini, Cells, 12. 2023-09-21 10:31:00.
The relationship between cytoplasmic incompatibility and the obligate intracellular alphaproteobacteria Wolbachia has for a long time been reported. Although the molecular mechanisms responsible for this reproductive alteration are beginning to be understood, the effects of Wolbachia on germ cell structure and dynamics have not yet been fully investigated. We report here that the presence of Wolbachia in infected cysts of elongating spermatids is associated with major structural defects that become more evident in mature sperm. We find mitochondrial defects, an improper axoneme structure, reduced sperm numbers, and individualization failures. The large heterogeneous variety of the ultrastructural defects found in elongating spermatids and mature sperm provide the first cytological evidence for the reduced fertility associated with Wolbachia infection in Drosophila simulans males. The observed abnormalities could be the result of the mechanical stress induced by the high bacteria numbers during the process of spermatid elongation, rather than the result of the released factors affecting the proper morphogenesis of the germ cells. Moreover, high Wolbachia densities in male germ cells may not be appropriate for causing cytoplasmic incompatibility as the bacteria are harmful for spermatid differentiation, leading to abnormal sperm that is unlikely to be functional.
Effect of 2 sex-sorting time schedules on SIT facility management
28345M. Malfacini, A. Puggioli, F. Balestrino, M. Carrieri, M. L. Dindo and R. Bellini, Journal of Insect Science, 23:9. 2023-09-18 10:58:06.
Improvements are needed in mosquito mass-rearing to effectively implement the sterile insect technique (SIT). However, managing this technique is challenging and resource intensive. SIT relies on mass rearing, sterilization, and release of adult males to reduce field populations. Maintaining an acceptable level of female presence, who can transmit viruses through biting, is crucial. Females are also essential for facility sustainability. Sex sorting plays a vital role in the production process, and our current mechanical sorting approach aims to obtain a high number of adult males with minimal female contamination within 24 h of pupation. Utilizing protandry helps control female contamination. While the 24-h sorting period achieves desired contamination levels, it may not yield enough females to sustain breeding lines, leading to increased labor costs that impact project sustainability. By delaying the sorting procedure to 48 h, we obtained sufficient females to sustain breeding lines, achieving a balance between male production and female contamination using the automatic version of the Fay–Morlan device as the sorting tool.
Development and characterization of microsatellite markers for the tsetse species Glossina brevipalpis and preliminary population genetics analyses
27882F. Gstöttenmayer, P. Moyaba, M. Rodriguez, F. C. Mulandane, H. N. Mucache, L. Neves, C. De Beer, S. Ravel, T. De Meeûs, R. L. Mach, M. J. B. Vreysen and A. M. M. Abd-Alla, Parasite, 30:34. 2023-09-15 08:27:06.
Tsetse flies, the vectors of African trypanosomes are of key medical and economic importance and one of the constraints for the development of Africa. Tsetse fly control is one of the most effective and sustainable strategies used for controlling the disease. Knowledge about population structure and level of gene flow between neighbouring populations of the target vector is of high importance to develop appropriate strategies for implementing effective management programmes. Microsatellites are commonly used to identify population structure and assess dispersal of the target populations and have been developed for several tsetse species but were lacking for Glossina brevipalpis. In this study, we screened the genome of G. brevipalpis to search for suitable microsatellite markers and nine were found to be efficient enough to distinguish between different tsetse populations. The availability of these novel microsatellite loci will help to better understand the population biology of G. brevipalpis and to assess the level of gene flow between different populations. Such information will help with the development of appropriate strategies to implement the sterile insect technique (SIT) in the framework of an area-wide integrated pest management (AW-IPM) approach to manage tsetse populations and ultimately address the trypanosomoses problem in these targeted areas.
Quantifying Fitness Costs in Transgenic Aedes aegypti Mosquitoes
27981I. Sanchez-Vargas, A. E. Williams, L. E. Martin, I. Martin-Martin, S. Bennett, K. E. Olson and E. Calvo, Journal of Visualized Experiments, 2023-09-15 07:51:42.
Transgenic mosquitoes often display fitness costs compared to their wild-type counterparts. In this regard, fitness cost studies involve collecting life parameter data from genetically modified mosquitoes and comparing them to mosquitoes lacking transgenes from the same genetic background. This manuscript illustrates how to measure common life history traits in the mosquito Aedes aegypti, including fecundity, wing size and shape, fertility, sex ratio, viability, development times, male contribution, and adult longevity. These parameters were chosen because they reflect reproductive success, are simple to measure, and are commonly reported in the literature. The representative results quantify fitness costs associated with either a gene knock-out or a single insertion of a gene drive element. Standardizing how life parameter data are collected is important because such data may be used to compare the health of transgenic mosquitoes generated across studies or to model the transgene fixation rate in a simulated wild-type mosquito population. Although this protocol is specific for transgenic Aedes aegypti, the protocol may also be used for other mosquito species or other experimental treatment conditions, with the caveat that certain biological contexts may require special adaptations.
Using Wolbachia to control rice planthopper populations: progress and challenges
27976Y. Guo, J. Shao, Y. Wu and Y. Li, Frontiers in Microbiology, 14. 2023-09-14 07:43:50.
Wolbachia have been developed as a tool for protecting humans from mosquito populations and mosquito-borne diseases. The success of using Wolbachia relies on the facts that Wolbachia are maternally transmitted and that Wolbachia-induced cytoplasmic incompatibility provides a selective advantage to infected over uninfected females, ensuring that Wolbachia rapidly spread through the target pest population. Most transinfected Wolbachia exhibit a strong antiviral response in novel hosts, thus making it an extremely efficient technique. Although Wolbachia has only been used to control mosquitoes so far, great progress has been made in developing Wolbachia-based approaches to protect plants from rice pests and their associated diseases. Here, we synthesize the current knowledge about the important phenotypic effects of Wolbachia used to control mosquito populations and the literature on the interactions between Wolbachia and rice pest planthoppers. Our aim is to link findings from Wolbachia-mediated mosquito control programs to possible applications in planthoppers.
Measuring the Impact of Genetic Heterogeneity and Chromosomal Inversions on the Efficacy of CRISPR-Cas9 Gene Drives in Different Strains of Anopheles gambiae
27837Pescod, Poppy Bevivino, Giulia Anthousi, Amalia Shelton, Ruth Shepherd, Josephine Lombardo, Fabrizio Nolan, Tony, The CRISPR Journal, 2023-09-13 09:06:32.
The human malaria vector Anopheles gambiae is becoming increasingly resistant to insecticides, spurring the development of genetic control strategies. CRISPR-Cas9 gene drives can modify a population by creating double-stranded breaks at highly specific targets, triggering copying of the gene drive into the cut site (?homing?), ensuring its inheritance. The DNA repair mechanism responsible requires homology between the donor and recipient chromosomes, presenting challenges for the invasion of laboratory-developed gene drives into wild populations of target species An. gambiae species complex, which show high levels of genome variation. Two gene drives (vas2-5958 and zpg-7280) were introduced into three An. gambiae strains collected across Africa with 5.3?6.6% variation around the target sites, and the effect of this variation on homing was measured. Gene drive homing across different karyotypes of the 2La chromosomal inversion was also assessed. No decrease in gene drive homing was seen despite target site heterology, demonstrating the applicability of gene drives to wild populations.
Mimicking superinfection exclusion disrupts alphavirus infection and transmission in the yellow fever mosquito Aedes aegypti
27839Reitmayer, Christine M. Levitt, Emily Basu, Sanjay Atkinson, Barry Fragkoudis, Rennos Merits, Andres Lumley, Sarah Larner, Will Diaz, Adriana V. Rooney, Sara Thomas, Callum J. E. von Wyschetzki, Katharina Rausalu, Kai Alphey, Luk, Proceedings of the National Academy of Sciences, 120:e2303080120. 2023-09-12 09:18:45.
Multiple viruses, including pathogenic viruses, bacteriophages, and even plant viruses, cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the nonstructural polyproteins (P123 and P1234) into individual proteins (nsP1?nsP4), forming the viral replication complex. Taking a synthetic biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titers, and transmission potential in mosquitoes.
MGDrivE 3: A decoupled vector-human framework for epidemiological simulation of mosquito genetic control tools and their surveillance
27894A. Mondal, C. H. M. Sanchez and J. M. Marshall, bioRxiv, 2023.09.09.556958. 2023-09-12 08:11:56.
We present MGDrivE 3 (Mosquito Gene Drive Explorer 3), a new version of a previously-developed framework, MGDrivE 2, that investigates the spatial population dynamics of mosquito genetic control systems and their epidemiological implications. The new framework incorporates three major developments: i) a decoupled sampling algorithm allowing the vector portion of the MGDrivE framework to be paired with a more detailed epidemiological framework, ii) a version of the Imperial College London malaria transmission model, which incorporates age structure, various forms of immunity, and human and vector interventions, and iii) a surveillance module that tracks mosquitoes captured by traps throughout the simulation. Example MGDrivE 3 simulations are presented demonstrating the application of the framework to a CRISPR-based homing gene drive linked to dual disease-refractory genes and their potential to interrupt local malaria transmission. Simulations are also presented demonstrating surveillance of such a system by a network of mosquito traps. MGDrivE 3 is freely available as an open-source R package on CRAN (https://cran.r-project.org/package=MGDrivE2) (version 2.1.0), and extensive examples and vignettes are provided.
Quantifying the impact of Wolbachia releases on dengue infection in Townsville, Australia
27831Ogunlade, S. T. Adekunle, A. I. Meehan, M. T. McBryde, E. S., Scientific Reports, 13:14932. 2023-09-11 08:51:39.
From October 2014 to February 2019, local authorities in Townsville, North Queensland, Australia continually introduced Wolbachia-infected mosquitoes to control seasonal outbreaks of dengue infection. In this study, we develop a mathematical modelling framework to estimate the effectiveness of this intervention as well as the relative dengue transmission rates of Wolbachia-infected and wild-type mosquitoes. We find that the transmission rate of Wolbachia-infected mosquitoes is reduced approximately by a factor of 20 relative to the uninfected wild-type population. In addition, the Townsville Wolbachia release program led to a 65% reduction in predicted dengue incidence during the release period and over 95% reduction in the 24 months that followed. Finally, to investigate the potential impact of other Wolbachia release programs, we use our estimates of relative transmissibility to calculate the relationship between the reproductive number of dengue and the proportion of Wolbachia-infected mosquitoes in the vector population.
New perspectives on the causes and consequences of male meiotic drive
27827Courret, Cécile Wei, Xiaolu Larracuente, Amanda M., Current Opinion in Genetics & Development, 2023-09-11 08:34:27.
Gametogenesis is vulnerable to selfish genetic elements that bias their transmission to the next generation by cheating meiosis. These so-called meiotic drivers are widespread in plants, animals, and fungi and can impact genome evolution. Here, we summarize recent progress on the causes and consequences of meiotic drive in males, where selfish elements attack vulnerabilities in spermatogenesis. Advances in genomics provide new insights into the organization and dynamics of driving chromosomes in natural populations. Common themes, including small RNAs, gene duplications, and heterochromatin, emerged from these studies. Interdisciplinary approaches combining evolutionary genomics with molecular and cell biology are beginning to unravel the mysteries of drive and suppression mechanisms. These approaches also provide insights into fundamental processes in spermatogenesis and chromatin regulation.
