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.
From the Lab to the Field: Long-Distance Transport of Sterile Aedes Mosquitoes
24750H. Maïga, M. T. Bakhoum, W. Mamai, G. Diouf, N. S. Bimbilé Somda, T. Wallner, C. Martina, S. S. Kotla, O. B. Masso, H. Yamada, B. B. D. Sow, A. G. Fall and J. Bouyer, Insects, 14. 2023-02-18 19:03:39.
Pilot programs of the sterile insect technique (SIT) against Aedes aegypti may rely on importing significant and consistent numbers of high-quality sterile males from a distant mass rearing factory. As such, long-distance mass transport of sterile males may contribute to meet this requirement if their survival and quality are not compromised. This study therefore aimed to develop and assess a novel method for long-distance shipments of sterile male mosquitoes from the laboratory to the field. Different types of mosquito compaction boxes in addition to a simulation of the transport of marked and unmarked sterile males were assessed in terms of survival rates/recovery rates, flight ability and morphological damage to the mosquitoes. The novel mass transport protocol allowed long-distance shipments of sterile male mosquitoes for up to four days with a nonsignificant impact on survival (>90% for 48 h of transport and between 50 and 70% for 96 h depending on the type of mosquito compaction box), flight ability, and damage. In addition, a one-day recovery period for transported mosquitoes post-transport increased the escaping ability of sterile males by more than 20%. This novel system for the long-distance mass transport of mosquitoes may therefore be used to ship sterile males worldwide for journeys of two to four days. This study demonstrated that the protocol can be used for the standard mass transport of marked or unmarked chilled Aedes mosquitoes required for the SIT or other related genetic control programs.
Wbm0076, a candidate effector protein of the Wolbachia endosymbiont of Brugia malayi, disrupts eukaryotic actin dynamics
24745M. K. Mills, L. G. McCabe, E. M. Rodrigue, K. F. Lechtreck and V. J. Starai, PLoS Pathogens, 19:e1010777. 2023-02-17 18:26:34.
Brugia malayi, a parasitic roundworm of humans, is colonized by the obligate intracellular bacterium, Wolbachia pipientis. The symbiosis between this nematode and bacterium is essential for nematode reproduction and long-term survival in a human host. Therefore, identifying molecular mechanisms required by Wolbachia to persist in and colonize B. malayi tissues will provide new essential information regarding the basic biology of this endosymbiosis. Wolbachia utilize a Type IV secretion system to translocate so-called "effector" proteins into the cytosol of B. malayi cells to promote colonization of the eukaryotic host. However, the characterization of these Wolbachia secreted proteins has remained elusive due to the genetic intractability of both organisms. Strikingly, expression of the candidate Wolbachia Type IV-secreted effector protein, Wbm0076, in the surrogate eukaryotic cell model, Saccharomyces cerevisiae, resulted in the disruption of the yeast actin cytoskeleton and inhibition of endocytosis. Genetic analyses show that Wbm0076 is a member of the family of Wiskott-Aldrich syndrome proteins (WAS [p]), a well-conserved eukaryotic protein family required for the organization of actin skeletal structures. Thus, Wbm0076 likely plays a central role in the active cell-to-cell movement of Wolbachia throughout B. malayi tissues during nematode development. As most Wolbachia isolates sequenced to date encode at least partial orthologs of wBm0076, we find it likely that the ability of Wolbachia to directly manipulate host actin dynamics is an essential requirement of all Wolbachia endosymbioses, independent of host cell species.
How genomics can help biodiversity conservation
24754K. Theissinger, C. Fernandes, G. Formenti, I. Bista, P. R. Berg, C. Bleidorn, A. Bombarely, A. Crottini, G. R. Gallo, J. A. Godoy, S. Jentoft, J. Malukiewicz, A. Mouton, R. A. Oomen, S. Paez, P. J. Palsbøll, C. Pampoulie, M. J. Ruiz-López, S. Secomandi, H, Trends in Genetics, 2023-02-16 19:11:36.
Genomics provides effective tools to characterize biodiversity, but the full implementation of genomic techniques in practical conservation is still limited. We review some of the main approaches in biodiversity genomics available to conservationists and genomicists.High-quality, long-read sequencing and bioinformatic technologies facilitate genome sequencing and assembly for any species. We summarize how reference genomes, in conjunction with population genomic data, can contribute to biodiversity monitoring, conservation, and restoration efforts.Over the past decade, many initiatives to generate reference genomes spanning the tree of life have emerged worldwide. We call for increased integration of reference genomes and population genomics data into interdisciplinary conservation efforts to fully unlock the potential of genomics in safeguarding global biodiversity.
Evaluating the mating competency of genetically modified male mosquitoes in laboratory conditions
28160B. Contreras, Z. N. Adelman and K. Chae, Frontiers in Tropical Diseases, 4. 2023-02-13 12:01:23.
Efforts to eradicate mosquito-borne diseases have increased the demand for genetic control strategies, many of which involve the release of genetically modified (GM) mosquito males into natural populations. The first hurdle for GM males is to compete with their wild-type counterparts for access to females. Here, we introduce an eye color-based mating assay, in which both Lvp wild-type and kynurenine 3-monooxygenase (kmo)-null males compete for access to kmo-null females, and therefore the eye color phenotype (black or white) of the progeny is dependent on the parental mating pair. A series of tests addressed that male mating competitiveness between the two strains can significantly be influenced by adult density, light intensity, and mating duration. Interestingly, the mating competitiveness of males was not correlated with body size, which was negatively influenced by a high larval density. Lastly, this eye color-associated assay was applied to characterize GM mosquitoes in their mating competitiveness, establishing this method as a fast and precise way of benchmarking this fitness parameter for laboratory-raised males.
Gene Drive: Past, Present and Future Roads to Vertebrate Biocontrol
24780G. R. McFarlane, C. B. A. Whitelaw and S. G. Lillico, Applied Biosciences, 2:52-70. 2023-02-13 09:35:36.
Scientists have long sought a technology to humanely control populations of damaging invasive pests in a species-specific manner. Gene drive technology could see this become a reality. This review charts the twists and turns on the road to developing gene drives in vertebrates. We focus on rodents, as these will likely be the first targets, and trace the journey from the early understanding of selfish genetic elements to engineering gene drives in mice; before discussing future research focuses and the crucial role that public perception and governance will play in the application of this technology. The realisation of robust gene drive strategies in vertebrate pests has the potential to revolutionise biocontrol.
Review of gene drive modelling and implications for risk assessment of gene drive organisms
24722J. L. Frieß, C. R. Lalyer, B. Giese, S. Simon and M. Otto, Ecological Modelling, 478:110285. 2023-02-13 09:34:10.
Synthetic gene drive (GD) systems constitute a form of novel invasive environmental biotechnology with far-reaching consequences beyond those of other known genetically modified organisms (GMOs). During the last 10 years, the development of GD systems has been closely linked to mathematical modelling which can provide feedback on how to achieve gene drive spread but also may be used to predict the ecological consequences of a gene drive release. GMOs, thus also GD systems, need to pass an environmental risk assessment (ERA) prior to a release into the environment. Models in this respect may play an important role because a release of GD organisms, even at a small scale, may not be reversible. In our review, we analyse the scope and structure of existing models to examine how they may assist the ERA. Our analysis reveals that a majority of models so far are deterministic, non-spatial and not tailored for a specific target organism. Models often use simplified assumptions on the biology of the species and seem to be made to test the effectiveness of the drive. Few models go beyond this and verify whether model predictions may be realistic under field conditions. We identified four advanced models that we judged to be the most ecologically realistic and compared the implemented parameters with ERA requirements by the European Food Safety Authority (EFSA) and World Health Organization (WHO) for genetically modified insects and mosquitoes. Although a number of abiotic and biotic factors are already considered in these models, mating-related factors and traits relevant to the interactions between the GMO and target organisms and with other species are largely excluded. Overall, our results show that biological and ecological realism are still poorly realized in current models and that most models aim to predict efficacy rather than ecological effects. Given the complexity of natural ecosystems, it may not be possible to compile a single model to cover all complexities. Thus, models should be further developed with the purpose to assist specific questions related to the risk assessment of GDs. Moreover, uncertainty will be a key issue for any model used in RA and we see the need to improve this aspect when modelling gene drives.
The Anthropocene as the End of Nature? Why Recognizing Interventionism Is Key in Coming to Terms with the Anthropocene
24729K. Boersma, ENVIRONMENTAL ETHICS, 44:195-219. 2023-02-12 09:43:02.
In this article, I address and argue against the tendency to understand the anthropocene as inaugurating the end of nature. I conduct two key moves. First, by way of an engagement with the concept of anthropocene technology I explain how understanding the anthropocene as the end of nature prevents us from recognizing what the anthropocene is all about: interventionism. Secondly, I illustrate how a nondualist understanding of the human-nature relation allows us to recognize interventionism as the hallmark of the anthropocene without falling back into the hierarchical human-nature conceptions that underlie interventionism. A nondualist framework that conserves the human-nature distinction helps us in our ability to relate critically to contemporary science and technology in the anthropocene. I illustrate the conceptual narrative of the article through the specific case of gene drive technology development.
Expansion and loss of sperm nuclear basic protein genes in Drosophila correspond with genetic conflicts between sex chromosomes
24732C.-H. Chang, I. Mejia Natividad and H. S. Malik, eLife, 12:e85249. 2023-02-10 09:47:51.
Many animal species employ sperm nuclear basic proteins (SNBPs) or protamines to package sperm genomes tightly. SNBPs vary across animal lineages and evolve rapidly in mammals. We used a phylogenomic approach to investigate SNBP diversification in Drosophila species. We found that most SNBP genes in Drosophila melanogaster evolve under positive selection except for genes essential for male fertility. Unexpectedly, evolutionarily young SNBP genes are more likely to be critical for fertility than ancient, conserved SNBP genes. For example, CG30056 is dispensable for male fertility despite being one of three SNBP genes universally retained in Drosophila species. We found 19 independent SNBP gene amplification events that occurred preferentially on sex chromosomes. Conversely, the montium group of Drosophila species lost otherwise-conserved SNBP genes, coincident with an X-Y chromosomal fusion. Furthermore, SNBP genes that became linked to sex chromosomes via chromosomal fusions were more likely to degenerate or relocate back to autosomes. We hypothesize that autosomal SNBP genes suppress meiotic drive, whereas sex-chromosomal SNBP expansions lead to meiotic drive. X-Y fusions in the montium group render autosomal SNBPs dispensable by making X-versus-Y meiotic drive obsolete or costly. Thus, genetic conflicts between sex chromosomes may drive SNBP rapid evolution during spermatogenesis in Drosophila species.
When less is more: accounting for overcompensation in mosquito SIT projects
24717J. Bouyer, Trends in Parasitology, 2023-02-08 10:14:35.
Compensation and overcompensation under field conditions are confirmed in Aedes mosquitoes recently by Evans et al.: equal or increased densities of emerging adults may thus result from reduced larval densities. Here the consequences when applying the sterile insect technique and provide recommendations to avoid counterproductive effects are discussed.
NDUFA8 potentially rescues Wolbachia-induced cytoplasmic incompatibility in Laodelphax striatellus
24743J. Chen, M. K. Wang, Q. X. Xie, X. L. Bing, T. P. Li and X. Y. Hong, Insect Sci, 2023-02-06 18:20:35.
The endosymbiont Wolbachia manipulates host reproduction by several strategies, one of the most important of which is cytoplasmic incompatibility (CI). CI can be rescued when Wolbachia-infected (WI) males mate with females infected with the same Wolbachia strain. However, the potential rescue mechanism of CI in the small brown planthopper Laodelphax striatellus is unclear. In this study, comparative transcriptome analysis was applied to explore the effect of Wolbachia on L. striatellus eggs. A total of 1387 differentially expressed genes were identified. RNAi of seven Wolbachia-upregulated key planthopper genes reduced egg reproduction, suggesting that Wolbachia might improve fecundity in L. striatellus by affecting these seven genes. Suppressing the expression of another upregulated gene, NDUFA8 (encoding NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8-like) by RNAi significantly increased the mortality of early embryos without affecting the number of deposited eggs. Wolbachia infection upregulated the mRNA level of NDUFA8, and dsNDUFA8 treatment of WI females re-created CI-like symptoms, suggesting that NDUFA8 is associated with the rescue phenotype. Because all L. striatellus populations worldwide are infected with Wolbachia, NDUFA8 is a potential pest control target. This article is protected by copyright. All rights reserved.
Investigating Wolbachia symbiont-mediated host protection against a bacterial pathogen using a natural Wolbachia nuclear insert
24740C. Prigot-Maurice, B. Lheraud, S. Guéritault, S. Beltran-Bech, R. Cordaux, J. Peccoud and C. Braquart-Varnier, Journal of Invertebrate Pathology, 197:107893. 2023-02-06 18:15:04.
Wolbachia bacterial endosymbionts provide protection against pathogens in various arthropod species but the underlying mechanisms remain misunderstood. By using a natural Wolbachia nuclear insert (f-element) in the isopod Armadillidium vulgare, we explored whether Wolbachia presence is mandatory to observe protection in this species or the presence of its genes is sufficient. We assessed survival of closely related females carrying or lacking the f-element (and lacking Wolbachia) challenged with the bacterial pathogen Salmonella enterica. Despite marginal significant effects, the f-element alone did not appear to confer survival benefits to its host, suggesting that Wolbachia presence in cells is crucial for protection.
A Zika virus-responsive sensor-effector system in Aedes aegypti
24699S. Basu, C. M. Reitmayer, S. Lumley, B. Atkinson, M. L. Schade-Weskott, S. Rooney, W. Larner, E. E. Montiel, R. Gutierrez-Lopez, E. Levitt, H. M. Munyanduki, A. M. E. Elrefaey, A. T. Clarke, S. Koit, E. Zusinaite, R. Fragkoudis, A. Merits and L. Alphey, bioRxiv, 2023.02.06.527261. 2023-02-06 12:38:46.
Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted primarily through the bite of an infected mosquito, Aedes aegypti being the main vector. ZIKV infection is associated with a range of adverse effects; infection during pregnancy can lead to foetal abnormalities, including microcephaly. Lacking a licensed vaccine, or specific therapeutics, control of ZIKV transmission focuses on vector control. However, in most transmission settings, current methods are insufficient to successfully control ZIKV, or other similarly-transmitted arboviruses such as dengue and chikungunya viruses. This has stimulated interest in genetics-based methods, either to reduce the number of mosquitoes (population suppression), or to make mosquitoes less able to transmit (population modification). Here, we describe a method to selectively eliminate infected mosquitoes, using a virus sensor inserted into the mosquito genome and coupled to a quorum-counting lethal effector. In mosquitoes, ZIKV normally establishes persistent, lifelong infection; survival of these infected mosquitoes is crucial to transmission potential. Correspondingly, removal of infected mosquitoes can reduce vectorial capacity of a mosquito population, i.e. ability to transmit. Since relatively few mosquitoes become infected, typically <2%, engineered hypersensitivity to ZIKV would have only a modest population-level fitness cost, and lower still if transmission were successfully reduced by such means.Competing Interest StatementThe authors have declared no competing interest.
A selfish genetic element and its suppressor causes gross damage to testes in a fly
24697S. Lyth, A. Manser, G. Hurst, T. Price and R. Verspoor, bioRxiv, 2023.02.06.527273. 2023-02-06 12:34:06.
Selfish genetic elements (SGEs), specifically X-chromosome meiotic drive (XCMD), create huge conflicts within a hosts genome and can have profound effects on fertility. Suppressors are a common evolutionary response to XCMD to negate its costs. However, whether suppressors themselves can cause negative non-target effects remains understudied. Here, we examine whether the intragenomic conflicts created by XCMD and its suppressor affects gonad morphology in Drosophila subobscura. We found significant differences in testes, seminal vesicle, and accessory gland size depending on whether a male carried a non-driving X chromosome, an XCMD, and if the XCMD was suppressed. We also found the first evidence of extreme whole-organ damage to testes that is specifically associated with a suppressor of XCMD. Unlike other studies, our evidence suggests that XCMD in D. subobscura inflicts extreme damage on male gonads. This damage is most severe if both XCMD and its suppressor are both present. While costs of suppression have importance in theoretical models, they have largely been ignored in empirical XCMD systems. Overall, this study highlights that genetic conflict, created by SGEs and their suppressors, is a potent evolutionary force that can have major impacts on gonad development and gametogenesis.Competing Interest StatementThe authors have declared no competing interest.
Moving beyond narrow definitions of gene drive: Diverse perspectives and frames enable substantive dialogue among science and humanities teachers in the United States and United Kingdom
24692S. Hartley, A. Stelmach, J. A. Delborne and S. K. Barnhill-Dilling, Public Understanding of Science, 2023-02-06 08:31:02.
Gene drive is an emerging biotechnology with applications in global health, conservation and agriculture. Scientists are preparing for field trials, triggering debate about when and how to release gene-drive organisms. These decisions depend on public understandings of gene drive, which are shaped by language. While some studies on gene drive communication assume the need to persuade publics of expert definitions of gene drive, we highlight the importance of meaning-making in communication and engagement. We conducted focus groups with humanities and science teachers in the United Kingdom and United States to explore how different media framings stimulated discussions of gene drive. We found diversity in the value of these framings for public debate. Interestingly, the definition favoured by gene drive scientists was the least popular among participants. Rather than carefully curating language, we need opportunities for publics to make sense and negotiate the meanings of a technology on their own terms.
Pangenomic analysis of Wolbachia provides insight into the evolution of host adaptation and cytoplasmic incompatibility factor genes
24785B. Liu, Y. S. Ren, C. Y. Su, Y. Abe and D. H. Zhu, Frontiers in Microbiology, 14:1084839. 2023-02-03 09:44:36.
INTRODUCTION: The genus Wolbachia provides a typical example of intracellular bacteria that infect the germline of arthropods and filarial nematodes worldwide. Their importance as biological regulators of invertebrates, so it is particularly important to study the evolution, divergence and host adaptation of these bacteria at the genome-wide level. METHODS: Here, we used publicly available Wolbachia genomes to reconstruct their evolutionary history and explore their adaptation under host selection. RESULTS: Our findings indicate that segmental and single-gene duplications, such as DNA methylase, bZIP transcription factor, heat shock protein 90, in single monophyletic Wolbachia lineages (including supergroups A and B) may be responsible for improving the ability to adapt to a broad host range in arthropod-infecting strains. In contrast to A strains, high genetic diversity and rapidly evolving gene families occur in B strains, which may promote the ability of supergroup B strains to adapt to new hosts and their large-scale spreading. In addition, we hypothesize that there might have been two independent horizontal transfer events of cif genes in two sublineages of supergroup A strains. Interestingly, during the independent evolution of supergroup A and B strains, the rapid evolution of cif genes in supergroup B strains resulted in the loss of their functional domain, reflected in a possible decrease in the proportion of induced cytoplasmic incompatibility (CI) strains. DISCUSSION: This present study highlights for reconstructing of evolutionary history, addressing host adaptation-related evolution and exploring the origin and divergence of CI genes in each Wolbachia supergroup. Our results thus not only provide a basis for further exploring the evolutionary history of Wolbachia adaptation under host selection but also reveal a new research direction for studying the molecular regulation of Wolbachia- induced cytoplasmic incompatibility.
Horizontal gene transfer from plant to whitefly
24810T. Islam, R. B. Azad, S. H. Kasfy, A. A. Rahman and T. Z. Khan, Trends in Biotechnology, 2023-02-02 10:00:00.
The recent discovery of the horizontal transfer of a toxin-neutralizing gene from plant to whitefly (Bemisia tabaci), a polyphagous insect, sparked a new area of study. In this forum, we discuss some potential biotechnological applications of this newly discovered knowledge in the coevolutionary arms race between plants and whitefly.
Biological comparative study between Wolbachia-infected Aedes aegypti mosquito and Wolbachia-uninfected strain, Jeddah city, Saudi Arabia
24804A. G. Algamdi, F. M. Shaher and J. A. Mahyoub, Saudi J Biol Sci, 30:103581. 2023-02-02 08:32:08.
In this study, samples of Wolbachia-infected Aedes aegypti mosquitoes were collected from Al-Safa district in Jeddah city, Saudi Arabia. The presence of Wolbachia bacteria in mosquitoes was confirmed by PCR technique and they were reared and propagated in the laboratory. Comparative studies were conducted between Wolbachia-infected A. Aegypti and the Wolbachia-uninfected laboratory strain in terms of their ability to withstand drought, resist two types of insecticides and the activities of pesticide detoxification enzymes. The Wolbachia-infected A. aegypti strain proved less able to withstand the drought period, as the egg-hatching rate of the Wolbachia-uninfected strain was greater than that of the Wolbachia-infected strain after one, two and three months of dry periods. Compared to the Wolbachia-uninfected strain, the Wolbachia-infected strain demonstrated a relatively greater resistance to tested pesticides, namely Baton 100EC and Fendure 25EC which may be attributed to the higher levels of the detoxification enzymes glutathione-S-transferase and catalase and the lower levels of esterase and acetylcholine esterase.
Engineered Antiviral Sensor Targets Infected Mosquitoes
24617E. Dalla Benetta, A. J. Lopez-Denman, H.-H. Li, R. A. Masri, D. J. Brogan, M. Bui, T. Yang, M. Li, M. Dunn, M. J. Klein, S. Jackson, K. Catalan, K. R. Blasdell, P. Tng, I. Antoshechkin, L. S. Alphey, P. N. Paradkar and O. Akbari, bioRxiv, 2023.01.27.525922. 2023-01-27 09:22:47.
Escalating vector disease burdens pose significant global health risks, so innovative tools for targeting mosquitoes are critical. We engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR Cas13 and its potent collateral activity. Akin to a stealthy Trojan Horse hiding in stealth awaiting the presence of its enemy, REAPER remains concealed within the mosquito until an infectious blood meal is up taken. Upon target viral RNA infection, REAPER activates, triggering programmed destruction of its target arbovirus such as chikungunya. Consequently, Cas13 mediated RNA targeting significantly reduces viral replication and its promiscuous collateral activity can even kill infected mosquitoes. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission.Competing Interest StatementO.S.A is a founder of both Agragene, Inc. and 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. L.A is an adviser to Synvect, Inc and Biocentis Ltd., with financial interest in each. All other authors declare no competing interests.
Impact of randomised wmel Wolbachia deployments on notified dengue cases and insecticide fogging for dengue control in Yogyakarta City
24619C. Indriani, S. K. Tanamas, U. Khasanah, M. R. Ansari, Rubangi, W. Tantowijoyo, R. A. Ahmad, S. M. Dufault, N. P. Jewell, A. Utarini, C. P. Simmons and K. L. Anders, Glob Health Action, 16:2166650. 2023-01-26 09:27:00.
BACKGROUND: Releases of Wolbachia (wMel)-infected Aedes aegypti mosquitoes significantly reduced the incidence of virologically confirmed dengue in a previous cluster randomised trial in Yogyakarta City, Indonesia. Following the trial, wMel releases were extended to the untreated control areas, to achieve city-wide coverage of Wolbachia. OBJECTIVE: In this predefined analysis, we evaluated the impact of the wMel deployments in Yogyakarta on dengue hemorrhagic fever (DHF) case notifications and on the frequency of perifocal insecticide spraying by public health teams. METHODS: Monthly counts of DHF cases notified to the Yogyakarta District Health Office between January 2006 and May 2022 were modelled as a function of time-varying local wMel treatment status (fully- and partially-treated vs untreated, and by quintile of wMel prevalence). The frequency of insecticide fogging in wMel-treated and untreated areas was analysed using negative binomial regression. RESULTS: Notified DHF incidence was 83% lower in fully treated vs untreated periods (IRR 0.17 [95% CI 0.14, 0.20]), and 78% lower in areas with 80-100% wMel prevalence compared to areas with 0-20% wMel (IRR 0.23 [0.17, 0.30]). A similar intervention effect was observed at 60-80% wMel prevalence as at 80-100% prevalence (76% vs 78% efficacy, respectively). Pre-intervention, insecticide fogging occurred at similar frequencies in areas later randomised to wMel-treated and untreated arms of the trial. After wMel deployment, fogging occurred significantly less frequently in treated areas (IRR 0.17 [0.10, 0.30]). CONCLUSIONS: Deployments of wMel-infected Aedes aegypti mosquitoes resulted in an 83% reduction in the application of perifocal insecticide spraying, consistent with lower dengue case notifications in wMel-treated areas. These results show that the Wolbachia intervention effect demonstrated previously in a cluster randomised trial was also measurable from routine surveillance data.
Control of Aedes mosquito populations using recombinant microalgae expressing short hairpin RNAs and their effect on plankton
24615X. Fei, S. Xiao, X. Huang, Z. Li, X. Li, C. He, Y. Li, X. Zhang and X. Deng, PLOS Neglected Tropical Diseases, 17:e0011109. 2023-01-26 09:15:48.
New biocontrol strategies are urgently needed to combat vector-borne infectious diseases. This study presents a low-cost method to produce a potential mosquito insecticide that utilizes the microalgae released into suburban water sources to control mosquito populations. Chlorella microalgae are ubiquitous in local waters, which were chosen as the host for genetic transfection. This species facilitated the recombinant algae to adapt to the prevailing environmental conditions with rapid growth and high relative abundance. The procedure involved microalgae RNAi-based insecticides developed using short hairpin RNAs targeting the Aedes aegypti chitin synthase A (chsa) gene in Chlorella. These insecticides effectively silenced the chsa gene, inhibiting Aedes metamorphosis in the laboratory and simulatedfield trials. This study explored the impact of recombinant microalgae on the phytoplankton and zooplankton in suburban waters. High-throughput sequencing revealed that rapid reproduction of recombinant Chlorella indirectly caused the disappearance of some phytoplankton and reduced the protozoan species. This study demonstrated that a recombinant microalgae-based insecticide could effectively reduce the population of Aedes mosquitoes in the laboratory and simulated field trials. However, the impact of this technology on the environment and ecology requires further investigation.
Assessing potential hybridization between a hypothetical gene drive-modified Drosophila suzukii and nontarget Drosophila species
24610S. Wolf, J. Collatz, J. Enkerli, F. Widmer and J. Romeis, Risk Analysis, 2023-01-24 09:02:35.
Genetically engineered gene drives (geGD) are potentially powerful tools for suppressing or even eradicating populations of pest insects. Before living geGD insects can be released into the environment, they must pass an environmental risk assessment to ensure that their release will not cause unacceptable harm to non-targeted entities of the environment. A key research question concerns the likelihood that nontarget species will acquire the functional GD elements; such acquisition could lead to reduced abundance or loss of those species and to a disruption of the ecosystem services they provide. The main route for gene flow is through hybridization between the geGD insect strain and closely related species that co-occur in the area of release and its expected dispersal. Using the invasive spotted-wing drosophila, Drosophila suzukii, as a case study, we provide a generally applicable strategy on how a combination of interspecific hybridization experiments, behavioral observations, and molecular genetic analyses can be used to assess the potential for hybridization.
Complicated expansion trajectories of insertion sequences and potential association with horizontal transfer of Wolbachia DNA
24573Y. H. Miao, D. W. Huang and J. H. Xiao, Zoological Research, 44:273-275. 2023-01-22 08:41:24.
Insertion sequences (ISs) are the simplest structural transposable elements (TEs) in prokaryotes, consisting only of a transposase coding sequence and its bilateral short terminal inverted repeats. Due to their gradually streamlined genomic construction, TEs rarely exist in the genomes of obligate endosymbionts. However, TE content, especially ISs, is abundant in the genome of Wolbachia bacteria, obligate endosymbionts widespread in arthropods and nematodes. Although IS indels are reported to affect genome structure and gene function in Wolbachia, the distribution patterns, sources, and transfer trajectories of ISs remain poorly understood. Furthermore, whether IS transposition is associated with dynamic horizontal transfer of Wolbachia DNA is still unclear. Based on distribution patterns in supergroup A Wolbachia strains, ISs accounted for 11% of the genome of the Wolbachia strain wWpum, one of the highest IS genome coverages reported for Wolbachia to date. Three types of ISs showed rapid expansion in wWpum, possibly due to horizontal transfer from other Wolbachia strain supergroups or more distant prokaryotes. We also found the first evidence that ISs can carry flanking Wolbachia sequences for transposition, resulting in the horizontal transfer of Wolbachia DNA into the eukaryotic genome, thus implying a potential association between ISs and horizontal gene transfer from endosymbionts to eukaryotes.
Closing the gap to effective gene drive in Aedes aegypti by exploiting germline regulatory elements
24581M. A. E. Anderson, E. Gonzalez, J. X. D. Ang, L. Shackleford, K. Nevard, S. A. N. Verkuijl, M. P. Edgington, T. Harvey-Samuel and L. Alphey, Nature Communications, 14:338. 2023-01-20 09:00:46.
CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. While attempts have been made to develop such systems in Aedes aegypti, none have been able to match the high drive efficiency observed in Anopheles species. Here we generate Ae. aegypti transgenic lines expressing Cas9 using germline-specific regulatory elements and assess their ability to bias inheritance of an sgRNA-expressing element (kmo(sgRNAs)). Four shu-Cas9 and one sds3-Cas9 isolines can significantly bias the inheritance of kmo(sgRNAs), with sds3G1-Cas9 causing the highest average inheritance of ~86% and ~94% from males and females carrying both elements outcrossed to wild-type, respectively. Our mathematical model demonstrates that sds3G1-Cas9 could enable the spread of the kmo(sgRNAs) element to either reach a higher (by ~15 percentage point) maximum carrier frequency or to achieve similar maximum carrier frequency faster (by 12 generations) when compared to two other established split drive systems.
Both male and female meiosis contribute to non-Mendelian inheritance of parental chromosomes in interspecific plant hybrids (Lolium x Festuca)
24833J. Majka, M. Glombik, A. Dolezalova, J. Knerova, M. T. M. Ferreira, Z. Zwierzykowski, M. Duchoslav, B. Studer, J. Dolezel, J. Bartos and D. Kopecky, NEW PHYTOLOGIST, 2023-01-19 08:34:11.
Some interspecific plant hybrids show unequal transmission of chromosomes from parental genomes to the successive generations. It has been suggested that this is due to a differential behavior of parental chromosomes during meiosis. However, underlying mechanism is unknown. We analyzed chromosome composition of the F-2 generation of Festuca x Lolium hybrids and reciprocal backcrosses to elucidate effects of male and female meiosis on the shift in parental genome composition. We studied male meiosis, including the attachment of chromosomes to the karyokinetic spindle and gene expression profiling of the kinetochore genes. We found that Lolium and Festuca homoeologues were transmitted differently to the F-2 generation. Female meiosis led to the replacement of Festuca chromosomes by their Lolium counterparts. In male meiosis, Festuca univalents were attached less frequently to microtubules than Lolium univalents, lagged in divisions and formed micronuclei, which were subsequently eliminated. Genome sequence analysis revealed a number of non-synonymous mutations between copies of the kinetochore genes from Festuca and Lolium genomes. Furthermore, we found that outer kinetochore proteins NDC80 and NNF1 were exclusively expressed from the Lolium allele. We hypothesize that silencing of Festuca alleles results in improper attachment of Festuca chromosomes to karyokinetic spindle and subsequently their gradual elimination.
Joint FAO/IAEA Coordinated Research Project on Mosquito Handling, Transport, Release and Male Trapping Methods in Support of SIT Application to Control Mosquitoes
24566M. Gómez, B. J. Johnson, H. C. Bossin and R. Argilés-Herrero, Insects, 14. 2023-01-19 08:14:17.
The research carried out in the framework of this CRP generated key achievements in areas relevant to the SIT application to control mosquitoes. Among these outcomes, particular mentions must be given to the following: (1) Novel and efficient self-marking techniques were established to improve our understanding of male movement, competitiveness, survival, and potential interaction with closely related species post-release [7,8]. As the next step, these new marking systems will be upscaled and validated under operational conditions in SIT field projects targeting the Aedes species. (2) One of the techniques evaluated included the novel large-scale marking of male mosquitoes via administration of Rhodamine B via sugar feeding. The mentioned technique brings the advantage of marking all of the tissues of the mosquitoes, including sperm and seminal fluid, such that the mark can be retrieved and identified in mated females. Thus, the use of Rhodamine B enables researchers to estimate the sexual competitiveness of sterile male mosquitoes under field conditions [9,10].
Wolbachia Promotes Its Own Uptake by Host Cells
24576L. B. Nevalainen, E. M. Layton and I. L. G. Newton, Infection and Immunity, e0055722. 2023-01-17 08:49:38.
Wolbachia pipientis is an incredibly widespread bacterial symbiont of insects, present in an estimated 25 to 52% of species worldwide. Wolbachia is faithfully maternally transmitted both in a laboratory setting and in the wild. In an established infection, Wolbachia is primarily intracellular, residing within host-derived vacuoles that are associated with the endoplasmic reticulum. However, Wolbachia also frequently transfers between host species, requiring an extracellular stage to its life cycle. Indeed, Wolbachia has been moved between insect species for the precise goal of controlling populations. The use of Wolbachia in this application requires that we better understand how it initiates and establishes new infections. Here, we designed a novel method for live tracking Wolbachia cells during infection using a combination of stains and microscopy. We show that live Wolbachia cells are taken up by host cells at a much faster rate than dead Wolbachia cells, indicating that Wolbachia bacteria play a role in their own uptake and that Wolbachia colonization is not just a passive process. We also show that the host actin cytoskeleton must be intact for this to occur and that drugs that disrupt the actin cytoskeleton effectively abrogate Wolbachia uptake. The development of this live infection assay will assist in future efforts to characterize Wolbachia factors used during host infection.
Wolbachia RNase HI contributes to virus blocking in the mosquito Aedes aegypti
24468M. Hussain, G. Zhang, M. Leitner, L. M. Hedges and S. Asgari, iScience, 26:105836. 2023-01-15 08:41:00.
The endosymbiotic bacterium Wolbachia pipientis blocks replication of several arboviruses in transinfected Aedes aegypti mosquitoes. However, the mechanism of virus blocking remains poorly understood. Here, we characterized an RNase HI gene from Wolbachia, which is rapidly induced in response to dengue virus (DENV) infection. Knocking down w RNase HI using antisense RNA in Wolbachia-transinfected mosquito cell lines and A. aegypti mosquitoes led to increased DENV replication. Furthermore, overexpression of wRNase HI, in the absence of Wolbachia, led to reduced replication of a positive sense RNA virus, but had no effect on a negative sense RNA virus, a familiar scenario in Wolbachia-infected cells. Altogether, our results provide compelling evidence for the missing link between early Wolbachia-mediated virus blocking and degradation of viral RNA. These findings and the successful pioneered knockdown of Wolbachia genes using antisense RNA in cell line and mosquitoes enable new ways to manipulate and study the complex endosymbiont-host interactions.
Engineered symbiotic bacteria interfering Nosema redox system inhibit microsporidia parasitism in honeybees
24493H. Lang, H. Wang, H. Wang, X. Xie, X. Hu, X. Zhang and H. Zheng, bioRxiv, 2023.01.13.524015. 2023-01-14 16:42:03.
Nosema ceranae is an emergent microsporidia parasite of the European honey bee (Apis mellifera), which causes serious nosemosis implicated in honeybee colony losses worldwide. N. ceranae is an obligate intracellular eukaryotic parasite that mainly invades the midgut of honeybees. Recent studies find that bee gut microbiota is potentially involved in protecting against parasitism. Here, using laboratory-generated bees mono-associated with gut members, we find that Snodgrassella alvi inhibited microsporidia proliferation, potentially via the stimulation of host oxidant-mediated immune response. Accordingly, N. ceranae employs the thioredoxin and glutathione systems to defend against oxidative stress and maintain a balanced redox equilibrium, which is essential for the infection process. We knocked down the gene expression using nanoparticle-mediated RNA interference, which targets the γ-glutamyl-cysteine synthetase and thioredoxin reductase genes of microsporidia. It significantly reduces the spore load, confirming the importance of the antioxidant mechanism for the intracellular invasion of the N. ceranae parasite. Finally, we genetically modified the symbiotic S. alvi to deliver dsRNA corresponding to the genes involved in the redox system of the microsporidia. The engineered S. alvi induces RNA interference and represses parasite gene expression, thereby inhibits the parasitism by up to 99.8%. Specifically, N. ceranae was most suppressed by the recombinant strain corresponding to the glutathione synthetase or by a mixture of bacteria expressing variable dsRNA. Our findings extend our previous understanding of the protection of gut symbionts against N. ceranae and provide a symbiont-mediated RNAi system for inhibiting microsporidia infection in honeybees.Competing Interest StatementThe authors have declared no competing interest.
Dynamics of an impulsive reaction-diffusion mosquitoes model with multiple control measures
24571Y. Li, H. Zhao and K. Wang, Mathematical Biosciences and Engineering, 20:775-806. 2023-01-14 08:34:08.
It is well-known that mosquito control is one of the effective methods to reduce and prevent the transmission of mosquito-borne diseases. In this paper, we formulate a reaction-diffusion impulsive hybrid model incorporating Wolbachia, impulsively spraying of insecticides, spatial heterogeneity, and seasonality to investigate the control of mosquito population. The sufficient conditions for mosquito extinction or successful Wolbachia persistence in a population of natural mosquitoes are derived. More importantly, we give the estimations of the spraying times of insecticides during a period for achieving the mosquito extinction and population replacement in a special case. A global attractivity of the positive periodic solution is analyzed under appropriate conditions. Numerical simulations disclose that spatial heterogeneity and seasonality have significant impacts on the design of mosquitoes control strategies. It is suggested to combine biological control and chemical pulse control under certain situations to reduce the natural mosquitoes. Further, our results reveal that the establishment of a higher level of population replacement depends on the strain type of the Wolbachia and the high initial occupancy of the Wolbachia-infected mosquitoes.
Bypassing Mendel’s First Law: Transmission Ratio Distortion in Mammals
24587G. Friocourt, A. Perrin, P. A. Saunders, E. Nikalayevich, C. Voisset, C. Coutton, G. Martinez and F. Morel, International Journal Molecular Sciences, 24. 2023-01-13 10:43:58.
Mendel's law of segregation states that the two alleles at a diploid locus should be transmitted equally to the progeny. A genetic segregation distortion, also referred to as transmission ratio distortion (TRD), is a statistically significant deviation from this rule. TRD has been observed in several mammal species and may be due to different biological mechanisms occurring at diverse time points ranging from gamete formation to lethality at post-natal stages. In this review, we describe examples of TRD and their possible mechanisms in mammals based on current knowledge. We first focus on the differences between TRD in male and female gametogenesis in the house mouse, in which some of the most well studied TRD systems have been characterized. We then describe known TRD in other mammals, with a special focus on the farmed species and in the peculiar common shrew species. Finally, we discuss TRD in human diseases. Thus far, to our knowledge, this is the first time that such description is proposed. This review will help better comprehend the processes involved in TRD. A better understanding of these molecular mechanisms will imply a better comprehension of their impact on fertility and on genome evolution. In turn, this should allow for better genetic counseling and lead to better care for human families.
Single-cell transcriptome sequencing reveals Wolbachia-mediated modification in early stages of Drosophila spermatogenesis
24466W. Dou, B. Sun, Y. Miao, D. Huang and J. Xiao, Proceedings of the Royal Society B: Biological Sciences, 290:20221963. 2023-01-11 08:36:44.
Wolbachia are the most widely distributed intracellular bacteria, and their most common effect on host phenotype is cytoplasmic incompatibility (CI). A variety of models have been proposed to decipher the molecular mechanism of CI, among which the host modification (HM) model predicts that Wolbachia effectors play an important role in sperm modification. However, owing to the complexity of spermatogenesis and testicular cell-type heterogeneity, whether Wolbachia have different effects on cells at different stages of spermatogenesis or whether these effects are linked with CI remains unknown. Therefore, we used single-cell RNA sequencing to analyse gene expression profiles in adult male Drosophila testes that were infected or uninfected by Wolbachia. We found that Wolbachia significantly affected the proportion of different types of germ cells and affected multiple metabolic pathways in germ cells. Most importantly, Wolbachia had the greatest impact on germline stem cells, resulting in dysregulated expression of genes related to DNA compaction, and Wolbachia infection also influenced the histone-to-protamine transition in the late stage of sperm development. These results support the HM model and suggest that future studies on Wolbachia-induced CI should focus on cells in the early stages of spermatogenesis.
Heterogeneous distribution of sex ratio distorters in natural populations of the isopod Armadillidium vulgare
24464S. Durand, B. Lheraud, I. Giraud, N. Bech, F. Grandjean, T. Rigaud, J. Peccoud and R. Cordaux, Biology Letters, 19:20220457. 2023-01-11 08:32:10.
In the isopod Armadillidium vulgare, many females produce progenies with female-biased sex ratios, owing to two feminizing sex ratio distorters (SRD): Wolbachia endosymbionts and the f element. We investigated the distribution and population dynamics of these SRD and mitochondrial DNA variation in 16 populations from Europe and Japan. Confirming and extending results from the 1990s, we found that the SRD are present at variable frequencies in populations and that the f element is overall more frequent than Wolbachia. The two SRD never co-occur at high frequency in any population, suggesting an apparent mutual exclusion. We also detected Wolbachia or the f element in some males, which probably reflects insufficient titer to induce feminization or presence of masculinizing alleles. Our results are consistent with a single integration event of a Wolbachia genome in the A. vulgare genome at the origin of the f element, which contradicts an earlier hypothesis of frequent losses and gains. We identified strong linkage between Wolbachia strains and mitochondrial haplotypes, but no association between the f element and mitochondrial background. Our results open new perspectives on SRD evolutionary dynamics in A. vulgare, the evolution of genetic conflicts and their impact on the variability of sex determination systems.
Effects of gamma radiation on the vector competence of Aedes aegypti (diptera: Culicidae) to transmit Zika virus
24462E. B. da Silva, C. M. de Mendonça, D. R. D. Guedes, M. H. S. Paiva, J. d. A. Mendonça, E. S. F. Dias, S. G. L. Florêncio, A. Amaral, A. M. Netto, C. F. J. A. Lopes and M. A. V. de Melo-Santos, Acta Tropica, 239:106831. 2023-01-11 08:27:34.
One of the limitations of the Sterile Insect Technique (SIT), conventionally performed by ionizing radiation, regards separating males from females, which is not 100% effective. Some irradiated females may be released together with males in the field at SIT. The present study aimed to evaluate the influence of ionizing radiation on the ability of Aedes aegypti mosquitoes to transmit the Zika virus after exposing female pupae to a 40 Gy of gamma radiation. The results suggest that the genetic damage induced by exposure of females to this dose level promotes their total sterility, but it does not influence their vector competence. However, our data point out that ionizing radiation may decrease the proportion of infective mosquitoes.
Trust in science and scientists: Effects of social attitudes and motivations on views regarding climate change, vaccines and gene drive technology
24622H. G. W. Dixson, A. F. Komugabe-Dixson, F. Medvecky, J. Balanovic, H. Thygesen and E. A. MacDonald, Journal of Trust Research, 2023-01-10 09:31:54.
Trust in science and scientists (TSS) is an increasingly important topic with respect to how science is applied within society. However, its role regarding specific issues may vary depending upon other psychosocial factors. In this study, we investigated how trust interacts with social attitudes and motivations to shape views on scientific issues in New Zealand (N = 8,199; 74.7% New Zealand European, 55.1% female). The study went beyond TSS by including broader institutional trust alongside measures relating to support for inequality, status quo preservation and fear of the unknown. We focused on their effects on three issues: vaccines, climate change and genetic technology (gene drive). Although TSS was strongly associated with lower vaccine skepticism (B = -0.497, p < 0.01), and moderate support for gene drive (B = 0.231, p < 0.01), it had no meaningful effect on climate skepticism. Furthermore, trust differentially mediated the relationship between social motivations and responses to all three issues. Trust in science and scientists is therefore unlikely to represent a one-size-fits-all variable. We conclude that future research should consider what effects trust in institutions and TSS have with social attitudes and motivations over a range of technologies across the sciences.
Sterility of Aedes albopictus by X-ray Irradiation as an Alternative to γ-ray Irradiation for the Sterile Insect Technique
24424L.-M. Wang, N. Li, C.-P. Ren, Z.-Y. Peng, H.-Z. Lu, D. Li, X.-Y. Wu, Z.-X. Zhou, J.-Y. Deng, Z.-H. Zheng, R.-Q. Wang, Y.-N. Du, D.-Q. Wang and S.-Q. Deng, Pathogens, 12. 2023-01-06 10:18:19.
The mosquito Aedes albopictus can transmit various arboviral diseases, posing a severe threat to human health. As an environmentally friendly method, sterile insect technology (SIT) is considered an alternative to traditional methods such as chemical pesticides to control Ae. albopictus. In SIT, the sterility of male mosquitoes can be achieved by γ-ray or X-ray radiation. Compared with γ-rays, X-rays are easier to obtain, cheaper, and less harmful. However, there is a lack of comparative assessment of these two types of radiation for SIT under the same controlled conditions. Here, we compared the effects of X-ray and γ-ray radiation on the sterility of Ae. albopictus males under laboratory-controlled conditions. Neither type of radiation affected the number of eggs but significantly reduced the survival time and hatch rate. The same dose of γ-rays caused a higher sterility effect on males than X-rays but had a more significant impact on survival. However, X-rays could achieve the same sterility effect as γ-rays by increasing the radiation dose. For example, X-rays of 60 Gy induced 99% sterility, similar to γ-rays of 40 Gy. In the test of male mating competitiveness, the induced sterility and the male mating competitiveness index were also identical at the same release ratio (sterile males/fertile males). At a release ratio of 7:1, nearly 80% of eggs failed to hatch. Sterile males produced by X-ray and γ-ray radiation had similar male competitiveness in competition with field males. In conclusion, a higher dose of X-rays is required to achieve the same sterility effect, compared to γ-rays. When γ-rays are not readily available, high-dose X-rays can be used instead. This study provides data supporting the selection of more suitable radiation for the field release of sterile male mosquitoes.
Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drives
24363J. Chen, X. Xu and J. Champer, bioRxiv, 2023.01.06.522951. 2023-01-06 09:33:07.
New types of gene drives promise to provide increased flexibility, offering many options for confined modification or suppression of target populations. Among the most promising are CRISPR toxin-antidote gene drives, which disrupt essential wild-type genes by targeting them with Cas9/gRNA, resulting in their removal. This increases the frequency of the drive in the population. All these drives, plus homing modification rescue drives, rely on having an effective rescue element, which consists of a recoded version of the target gene. This rescue element can be at the same site as the target gene, which maximizes the chance of efficient rescue, or at a distant site, which allows some other useful options, such as easily disrupting another essential gene or achieving greater confinement. Previously, we developed a homing rescue drive targeting a haplolethal gene and a toxin-antidote drive targeting an essential but haplosufficient gene. These successful drives had functional rescue elements but suboptimal drive efficiency. Here, we attempted to construct new toxin-antidote drives targeting these genes with a distantsite configuration from three different loci. We found that use of additional gRNAs increased cut rates to nearly 100%. However, all distant-site rescue elements failed for both haplolethal and haplosufficient target genes. Furthermore, one rescue element with a minimally recoded rescue element was used as a template for homology-directed repair for the target gene on a different chromosomal arm, resulting in the formation of functional resistance alleles at high frequency. Together, these results can inform the design of future CRISPR-based toxin-antidote gene drives.Competing Interest StatementThe authors have declared no competing interest.
The Possibilities of Gene Drives for Managing Populations and Controlling Diseases
27641J. Vijay Upadhye, U. N. Shah and B. Mudhol, Salud, Ciencia y Tecnologia, 3. 2023-01-01 07:51:35.
The technical limitations and the use of gene drives to address ecological problems by modifying all populations of wild species remain primarily speculative. Here, we examine the possibility that RNA-guided gene drives based on the CRISPR nuclease Cas9 could be used as an all-encompassing approach for introducing changed features into natural populations over a long period. We outline potential capabilities and possible disadvantages and offer new preventative measures to stem from the propagation of genes and undo genetic modifications. Editing the sexual animal population would significantly benefit both people and the environment. For instance, RNA-guided gene drives may stop the spread of illness, assist farming by correcting bug and weed chemicals and resistance to herbicides, and manage harmful invasive species. However, each prospective use needs to be carefully evaluated due to the likelihood of unfavorable ecological repercussions and the near inevitability of dissemination beyond political boundaries. To investigate the responsible application of this now hypothetical technology, we want serious, inclusive, educated public conversations. © 2023; Los autores.
Gene drive designs for efficient and localisable population suppression using Y-linked editors
24339R. Geci, K. Willis and A. Burt, PLOS Genetics, 18:e1010550. 2022-12-27 08:45:03.
Author summary Some pest populations can be successfully controlled by the inundative release of sterile males, but this approach is not practicable when the target population is large or the species difficult to rear. Computer modelling has previously demonstrated that releasing males with a genomic editor on their Y chromosome that kills or sterilises female descendants could be much more efficient, particularly if combined with a sex ratio distorter. Here we extend this work to show that Y-linked editors can also be used in even more efficient gene drive designs that would spread over successive generations beyond the region of release. Such spread could nonetheless be controlled by exploiting relatively small pre-existing differences in gene frequency between populations to restrict the spread and impact of the constructs, if desired. The proposed design does not require high rates of recombinational repair of DNA breaks or expression off the Y chromosome during meiosis, potentially expanding the range of species in which such low release rate control is possible. Y-linked editors may therefore form the basis of a highly flexible set of genetic strategies for population control.
Survival-Larval Density Relationships in the Field and Their Implications for Control of Container-Dwelling Aedes Mosquitoes
24714K. G. Evans, Z. R. Neale, B. Holly, C. C. Canizela and S. A. Juliano, Insects, 14. 2022-12-23 10:10:37.
Population density can affect survival, growth, development time, and adult size and fecundity, which are collectively known as density-dependent effects. Container Aedes larvae often attain high densities in nature, and those densities may be reduced when larval control is applied. We tested the hypothesis that density-dependent effects on survival are common and strong in nature and could result in maximal adult production at intermediate densities for Aedes aegypti, Aedes albopictus, and Aedes triseriatus. We surveyed naturally occurring densities in field containers, then introduced larvae at a similar range of densities, and censused the containers for survivors. We analyzed the survival-density relationships by nonlinear regressions, which showed that survival-density relationships vary among seasons, sites, and species. For each Aedes species, some sites and times yielded predictions that larval density reduction would yield the same (compensation), or more (overcompensation), adults than no larval density reduction. Thus, larval control targeting these Aedes species cannot always be assumed to yield a reduction in the number of adult mosquitoes. We suggest that mosquito control targeting larvae may be made more effective by: Imposing maximum mortality; targeting populations when larval abundances are low; and knowing the shape of the survival-density response of the target population.
Mating Competitiveness of Irradiated Lobesia botrana (Lepidoptera: Tortricidae) in Male-Only and Both Sex Release Strategies under Laboratory Cage Conditions
24324G. Saour, A. Hashem and I. Jassem, Insects, 14. 2022-12-23 09:03:18.
This laboratory study explored the concept of whether irradiated male-only releases are more or equally efficient as releases of both irradiated males and females in the context of using the sterile insect technique/inherited sterility (SIT/IS) for the management of the European grapevine moth Lobesia botrana. The current study examined the mating competitiveness of 150-Gy-treated L. botrana male and female moths or 150-Gy-treated male moths only, with untreated moths in laboratory cages. Our results showed that the release of both sexes significantly increased the competitiveness value (C) and the biological efficiency index (BE) as compared with male-only release, and this was independent of the male to untreated male ratio. Moreover, a single release of 150-Gy-treated and untreated males and females at a 1:1:10:10 ratio (untreated male:untreated female: treated male:treated female) significantly reduced egg hatch, and the number of first-generation offspring (F1) was small. The emergence of F2-moths per untreated F1 male and female moth was low, but these undesired fertile moths should be eliminated in order to achieve effective control. The results presented herein provide useful information on the impact of 150-Gy-treated male-only, versus releases of both treated males and females on untreated moths, which is essential to managing L. botrana populations with SIT/IS.
Use of Insect Promoters in Genetic Engineering to Control Mosquito-Borne Diseases
24584V. Bottino-Rojas and A. A. James, Biomolecules, 13. 2022-12-22 10:33:51.
Mosquito transgenesis and gene-drive technologies provide the basis for developing promising new tools for vector-borne disease prevention by either suppressing wild mosquito populations or reducing their capacity from transmitting pathogens. Many studies of the regulatory DNA and promoters of genes with robust sex-, tissue- and stage-specific expression profiles have supported the development of new tools and strategies that could bring mosquito-borne diseases under control. Although the list of regulatory elements available is significant, only a limited set of those can reliably drive spatial-temporal expression. Here, we review the advances in our ability to express beneficial and other genes in mosquitoes, and highlight the information needed for the development of new mosquito-control and anti-disease strategies.
Genes drive organisms and slippery slopes
24322D. B. Resnik, R. F. Medina, F. Gould, G. Church and J. Kuzma, Pathog Glob Health, 2022-12-22 08:58:12.
The bioethical debate about using gene drives to alter or eradicate wild populations has focused mostly on issues concerning short-term risk assessment and management, governance and oversight, and public and community engagement, but has not examined big-picture- 'where is this going?'-questions in great depth. In other areas of bioethical controversy, big-picture questions often enter the public forum via slippery slope arguments. Given the incredible potential of gene drive organisms to alter the Earth's biota, it is somewhat surprising that slippery slope arguments have not played a more prominent role in ethical and policy debates about these emerging technologies. In this article, we examine a type of slippery slope argument against using gene drives to alter or suppress wild pest populations and consider whether it has a role to play in ethical and policy debates. Although we conclude that this argument does not provide compelling reasons for banning the use of gene drives in wild pest populations, we believe that it still has value as a morally instructive cautionary narrative that can motivate scientists, ethicists, and members of the public to think more clearly about appropriate vs. inappropriate uses of gene drive technologies, the long-term and cumulative and emergent risks of using gene drives in wild populations, and steps that can be taken to manage these risks, such as protecting wilderness areas where people can enjoy life forms that have not been genetically engineered.
P-element invasions in Drosophila erecta; shed light on the establishment of host control over a transposable element
24320D. Selvaraju, F. Wierzbicki and R. Kofler, bioRxiv, 2022.12.22.521571. 2022-12-22 08:52:45.
To prevent the spread of transposable elements (TEs) hosts have developed sophisticated defence mechanisms. In mammals and invertebrates this defence mechanism operates through piRNAs. It is unclear how piRNA-based defences are established against invading TEs. According to the trap model, a TE insertion into a piRNA cluster, i.e. a distinct genomic locus, activates the host defence. Alternatively, siRNAs, generated by cleavage of dsRNA, may be the trigger for host control. To investigate this we introduced the P-element, one of the most widely studied eukaryotic transposons, into naïve lines of Drosophila erecta. We monitored the invasion in 3 replicates for more than 50 generations by sequencing the genomic DNA (using short and long-reads), the small RNAs and the transcriptome at regular intervals. A piRNA based host defence was rapidly established in 2 replicates but not in the third, where P-element copy numbers kept increasing for over 50 generations. We found that siRNAs emerged prior to piRNAs, supporting the view that siRNAs initiate host defence. However, neither insertions in piRNA clusters nor the formation of siRNAs were sufficient to stop the P-element. Instead the activation of the ping-pong cycle was shown to be crucial. We introduce a novel model, the crank-up model, which emphasizes activation of the ping-pong cycle as a critical event in establishing host control over a TE.Competing Interest StatementThe authors have declared no competing interest.
Gene drive-mediated population elimination for biodiversity conservation. When you come to a fork in the road, take it
24281B. A. Hay and M. Guo, Proceedings of the National Academy of Sciences, 119:e2218020119. 2022-12-20 14:19:44.
How can the ability of t w2 to spread at super-Mendelian frequencies be utilized even if it is unable to directly drive the population to an unfit state? Gierus, Birand, and colleagues proposed placing Cas9 and a gRNA at a neutral position within the t haplotype. In this hybrid gene drive element, which they refer to as tCRISPR, Cas9 and the gRNA cleave and (hopefully) create loss-of-function (LOF) alleles in the male germ line of the prolactin (Prl) gene, which is required for female fertility. The goal with tCRISPR is for t-based segregation distortion in males to pump the Cas9/gRNAs cassette to high frequency within the population. The latter, through cleavage followed by inaccurate repair in males, will continuously produce LOF alleles at the independently segregating Prl locus. The hope is that the combination of t-based drive and accumulation of Prl LOF alleles will drive the population to an unfit state that contains a high frequency of infertile homozygous Prl mutant females along with some frequency of infertile homozygous t males. The combination of these two effects, they propose, could eliminate populations under a wider range of parameters than with t w2 alone
Gene editing and agrifood systems
24291FAO, FAO, 2022-12-20 09:22:56.
Gene-editing technologies represent a promising new tool for plant and animal breeding in low- and middle-income countries. They enhance precision and efficiency over current breeding methods and could lead to rapid development of improved plant varieties and animal breeds. However, as for any new technology, they have their merits and demerits. There is, as yet, no international consensus regarding if and how gene-edited organisms should be regulated, and whether their release would fall under the regulatory framework of the Cartagena Protocol on Biosafety to the Convention on Biological Diversity. This science- and evidence-based Issue Paper on gene editing and agrifood systems presents a balanced discussion of the most pertinent aspects of gene editing, including the consequences for human hunger, human health, food safety, effects on the environment, animal welfare, socioeconomic impact and distribution of benefits. Intrinsic ethical concerns and issues of governance and regulation are addressed, and the roles of the public and private sectors, alone and in partnership, are summarized. Various scenarios are also presented for how gene editing might be used in the future to help transform agrifood systems.
A Natural Fungal Gene Drive Enacts Killing via DNA Disruption
24286A. S. Urquhart and D. M. Gardiner, mBio, e0317322. 2022-12-20 08:53:56.
Fungal spore killers are a class of selfish genetic elements that positively bias their own inheritance by killing non-inheriting gametes following meiosis. As killing takes place specifically within the developing fungal ascus, a tissue which is experimentally difficult to isolate, our understanding of the mechanisms underlying spore killers are limited. In particular, how these loci kill other spores within the fungal ascus is largely unknown. Here, we overcome these experimental barriers by developing model systems in 2 evolutionary distant organisms, Escherichia coli (bacterium) and Saccharomyces cerevisiae (yeast), similar to previous approaches taken to examine the wtf spore killers. Using these systems, we show that the Podospora anserina spore killer protein SPOK1 enacts killing through targeting DNA. IMPORTANCE Natural gene drives have shaped the genomes of many eukaryotes and recently have been considered for applications to control undesirable species. In fungi, these loci are called spore killers. Despite their importance in evolutionary processes and possible applications, our understanding of how they enact killing is limited. We show that the spore killer protein Spok1, which has homologues throughout the fungal tree of life, acts via DNA disruption. Spok1 is only the second spore killer locus in which the cellular target of killing has been identified and is the first known to target DNA. We also show that the DNA disrupting activity of Spok1 is functional in both bacteria and yeast suggesting a highly conserved mode of action.
Wolbachia endosymbionts manipulate GSC self-renewal and differentiation to enhance host fertility
24270S. L. Russell, J. R. Castillo and W. T. Sullivan, bioRxiv, 2022.12.15.520626. 2022-12-17 14:03:40.
The alphaproteobacterium Wolbachia pipientis infects thousands of 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 often credited for catapulting these intracellular bacteria to high frequencies in their host populations. Positive, perhaps mutualistic, reproductive manipulations may also increase infection frequencies, but they are not well understood on molecular, cellular, or organismal levels. Previous studies demonstrated that Wolbachia is capable of partially rescuing sex-lethal, a gene required for germline stem cell (GSC) self renewal and bag-of-marbles, a gene required for GSC differentiation. Here, we identify molecular and cellular mechanisms by which Wolbachia is able to influence molecularly distinct processes of GSC self renewal and differentiation through our discovery that the wMel strain rescues meiotic-P26 mutants. Mei-P26 is an essential translational regulator and is required for both GSC self-renewal and differentiation. We demonstrate that wMel rescues the fertility of flies lacking adequate mei-P26 dosage and function, and is sufficient to sustain infertile homozygous mei-P26 hypomorphic stocks indefinitely. Cytology revealed that wMel infection mitigates the impact of mei-P26 loss on both germline stem cell maintenance and cyst differentiation through restoring proper pMad, Bam, Sxl, and Orb expression. Rescue in males, amplification of dominant negative effects, and multiallelic rescue suggest that wMel either directly or indirectly replaces Mei-P26 function. Even in wild-type individuals, wMel infection elevates lifetime egg lay and hatch rates. Over time, the beneficial fertility reinforcement mechanisms described here may promote the emergence of mutualism and the breakdown of CI.HighlightsThe wMel strain of Wolbachia restores fertility in females and males deficient for the essential translational regulator meiotic-P26Mei-P26’s germline maintenance and oocyte cyst differentiation functions are genetically rescued by wMel infectionPerturbed pMad, Sxl, Bam, and Orb expression are mitigated by wMel infectionwMel infection elevates lifetime egg lay and hatch rates in wild-type fliesCompeting Interest StatementThe authors have declared no competing interest.
Assessing the efficacy of male Wolbachia-infected mosquito deployments to reduce dengue incidence in Singapore: study protocol for a cluster-randomized controlled trial
24268J. Ong, S. H. Ho, S. X. H. Soh, Y. Wong, Y. Ng, K. Vasquez, Y. L. Lai, Y. X. Setoh, C. S. Chong, V. Lee, J. C. C. Wong, C. H. Tan, S. Sim, L. C. Ng and J. T. Lim, Trials, 23:1023. 2022-12-17 13:57:59.
The study is designed as a parallel, two-arm, non-blinded cluster-randomized (CR) controlled trial to be conducted in high-rise public housing estates in Singapore, an equatorial city-state. The aim is to determine whether large-scale deployment of male Wolbachia-infected Ae. aegypti mosquitoes can significantly reduce dengue incidence in intervention clusters. We will use the CR design, with the study area comprising 15 clusters with a total area of 10.9 km(2), covering approximately 722,204 residents in 1713 apartment blocks. Eight clusters will be randomly selected to receive the intervention, while the other seven will serve as non-intervention clusters. Intervention efficacy will be estimated through two primary endpoints:
Exploring the value of a global gene drive project registry
24279R. I. Taitingfong, C. Triplett, V. N. Vásquez, R. M. Rajagopalan, R. Raban, A. Roberts, G. Terradas, B. Baumgartner, C. Emerson, F. Gould, F. Okumu, C. E. Schairer, H. C. Bossin, L. Buchman, K. J. Campbell, A. Clark, J. Delborne, K. Esvelt, J. Fisher, R., Nature Biotechnology, 2022-12-15 14:15:40.
Recent calls to establish a global project registry before releasing any gene-drive-modified organisms (GDOs) have suggested a registry could be valuable to coordinate research, collect data to monitor and evaluate potential ecological impacts, and facilitate transparent communication with community stakeholders and the general public. Here, we report the results of a multidisciplinary expert workshop on GDO registries convened on 8–9 December 2020 involving 70 participants from 14 countries. Participants had expertise in gene drive design, conservation and population modeling, social science, stakeholder engagement, governance and regulation, international policy, and vector control; they represented 45 organizations, spanning national and local governmental agencies, international organizations, nonprofit organizations, universities, and district offices overseeing local vector control. The workshop aimed to gather perspectives on a central question: “In what ways could a gene-drive project registry both contribute to and detract from the fair development, testing and use of GDOs?” We specifically queried the perceived purpose of a registry, the information that would need to be included, and the perceived value of a registry. Three primary findings emerged from the discussion: first, many participants agreed a registry could serve a coordinating function for multidisciplinary and multisector work activities; second, doing so may require different design elements, depending on the target end-user group and intended purpose for that group; and third, these different information requirements lead to concerns about information sharing via a registry, suggesting potential obstacles to achieving transparency through such a mechanism. We conclude that any development of a gene-drive project registry requires careful and inclusive deliberation, including with potential end-users, to ensure that registry design is optimal.
Performance characteristics allow for confinement of a CRISPR toxin-antidote gene drive designed for population suppression
24272S. Zhang and J. Champer, bioRxiv, 2022.12.13.520356. 2022-12-15 14:08:18.
Gene drives alleles that can bias their own inheritance are a promising way to engineer populations for control of disease vectors, invasive species, and agricultural pests. Recent advancements in the field have yielded successful examples of powerful suppression type drives and confined modification type drives, but developing confined suppression drives has proven more difficult. This is because the necessary power for strong suppression is often incompatible with the characteristics needed for drive confinement. However, one type of CRISPR toxin-antidote drive may be strong enough and confined, the TADE (Toxin-Antidote Dominant Embryo) suppression drive. By disrupting a haplolethal target gene and a haplosufficient female fertility gene, this drive quickly eliminates wild-type alleles and eventually induces population suppression. It has been shown to perform effectively in panmictic populations. However, confinement in spatial scenarios may be substantially different. Here, we use a reaction-diffusion model to assess the performance of TADE suppression drive in continuous space. We measure the drive wave advance speed while varying several performance parameters and find that moderate fitness costs or embryo cutting (from maternally deposited nuclease) can eliminate the drive’s ability to form a wave of advance. We assess the release size required for the drive to propagate, and finally, we investigate migration corridor scenarios. Depending on the corridor size and dispersal, it is often possible for the drive to suppress one population and then persist in the corridor without invading the second population. This prevents re-invasion by wild-type, which may be a particularly desirable outcome in some scenarios. Thus, even imperfect variants of TADE suppression drive may be excellent candidates for confined population suppression.Competing Interest StatementThe authors have declared no competing interest.
