Keywords: Population genetics/dynamics
Compound effector genes suppress malaria parasite infections in gene-drive population modification strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
35494Rebeca Carballar-Lejarazú, Yuemei Dong, Thai Binh Pham, et al., G3 Genes|Genomes|Genetics, 2026-03-09 10:43:52.
Malaria remains a major global health burden and is caused by protozoan parasites in the genus Plasmodium. Parasites are transmitted to humans during blood feeding by anopheline mosquitoes, and members of the Anopheles gambiae species complex are important vectors in sub-Saharan Africa. Gene-drive technologies offer promising options for disease control by enabling the spread of genetic traits through mosquito populations that block parasite transmission. We report here the development and characterization of four population modification gene-drive strains in Anopheles gambiae s.s. and An. coluzzii carrying compound effector genes. We sought to enhance the effectiveness of existing gene-drive strains to block Plasmodium transmission, thereby reducing vector competence and minimizing the opportunities for selection of resistant parasites. Two compound effector gene modules, TP24 and TP43, were introduced using Cas9 endonuclease and dual guide RNAs into TP13-based gene-drive strains to produce the An. gambiae AgTP24 and AgTP43 strains. The gene-drive cassettes were then introgressed into An. coluzzii to produce AcTP24 and AcTP43. Gene-drive dynamics, gene conversion, and inheritance were high in all strains, with 95% to 100% inheritance of the gene-drive constructs. Life table analyses showed mixed impacts on fitness dependent on the species and copy number (hemi- or homozygosity) of the gene-drive systems. The compound effector molecule gene complexes significantly reduced both parasite prevalence and infection intensities in An. gambiae and An. coluzzii following challenge assays with the human malaria parasite, P. falciparum. These findings highlight the potential of compound effector strategies in gene-drive systems to achieve durable malaria transmission control.
Is a ‘selfish gene’ making a Utah family have twice as many boys as girls?
35478Ewen Callaway, Nature, 2026-02-27 18:24:37.
By sifting through an anonymized genealogy database, researchers have discovered a Utah family that has been having twice as many boys as girls for seven generations. It is the first clear evidence that humans might have ‘selfish genes’ that distort the sex ratio of offspring from roughly 50:50, the researchers argue in a preprint posted on bioRxiv earlier this month. The findings have not been peer-reviewed. Such sex ‘distorters’ have been discovered — and studied in great depth — in laboratory animals such as mice and flies, in which their effects can be detected through selective breeding. “If you look, more often than not, you find them,” says Nitin Phadnis, an evolutionary geneticist at the University of Utah in Salt Lake City, who co-led the study. Theoretical predictions suggest that sex distorters probably do exist in people as well, and that they could produce excesses of biological boys or girls at birth. But humans’ long generation times and low birth rates as well as ethical issues have made such genes — and other ‘selfish’ genetic elements , meaning that they bias their own transmission to future generations whether or not they improve an individual’s biological fitness — difficult to spot.
Emerging trends in genome editing of wild animals
35453Blix, T., Myhr, A.I., Transgenic Research, 35. 2026-02-06 09:37:20.
Globally, nearly one million species are currently threatened with extinction, highlighting the need for more efficient solutions to biological conservation. Genome editing, which allows for faster and more precise changes in genomes, is a promising technique for boosting populations through facilitated adaptation, management of invasive or pathogenic populations, and potentially even facilitating the revival of extinct species. These approaches belong to a new field of research termed conservation biotechnology, which places a great responsibility on researchers and decision makers to ensure sustainability. In this paper, we have mapped the emerging trends in genome editing of wild animals. Current projects primarily focus on population control and de-extinction, with fewer initiatives aimed at preserving threatened species. We then explore four critical dimensions of conservation biotechnology: the technology itself, new perspectives on conservation practices, research organization, and governance and policy. Despite its potential, key questions remain—particularly whether genome editing can increase genetic diversity without causing unintended non-target impacts. Genome editing also provokes new perspectives on conservation practices where ecosystem-wide impact assessment, case-by-case evaluations, and post-release monitoring needs to be prioritized. Furthermore, conservation biotechnology is heavily funded through private funding showing varying stakeholder interest, which can lead to untraditional and less transparent research processes. Stakeholders, including local and indigenous people, are only to a certain degree involved, which may weaken inclusion of local knowledge and monitoring efforts. Finally, concerning governance and policy, there is an urgent need to develop more adequate regulation of conservation biotechnology, as environmental release of genome-edited animals challenges definitions and guidelines in current nature protection laws and GMO regulations. Based on our analysis, we outline key points for further investigation toward a more sustainable approach to conservation biotechnology.
Field implementation of the sterile insect technique against Aedes aegypti in Recife, Brazil: operational challenges and impact of release frequency on vector dynamics
35418Macedo, A.T., Carvalho, D.O., Gomez, M. et al., Infectious Diseases of Poverty, 15. 2026-02-02 16:59:43.
The sterile insect technique (SIT) is an environmentally friendly tool for suppressing Aedes aegypti populations. While promising in controlled settings, its application in large urban environments presents logistical and biological challenges. This trial focused on releasing sterile males, sent from a long-distance production facility to suppress the local mosquito population. Sterile males of Ae. aegypti were mass-reared, irradiated, and transported 712.2 km from a central facility to Recife, Brazil. Releases were performed once (SIT 1 ×) or twice per week (SIT 2 ×). Entomological indices—including eggs/trap per day (ETD), hatch rate, induced sterility, and adult female abundance—were monitored through ovitraps and BG-Sentinel traps. Data were analyzed using generalized linear mixed models (GLMMs) and Bayesian time-series modeling (CausalImpact). Dose–response experiments established that pupae required 35 Gy and adults 65 Gy to achieve > 99% sterility, with no difference between gamma and X-ray sources. Adult sterilization was effective across 24–96 h post-emergence, facilitating operational flexibility. Handling and transport reduced flight ability by up to 35 percentage points, highlighting cumulative stress effects. In field trials, SIT 1 × yielded limited suppression, with ETD values remaining similar to or higher than those of the control. In contrast, SIT 2 × produced consistent suppression, reducing ETD by 39%, hatch rate by 33%, and female abundance by 51%. In this study, increasing the release frequency was essential to achieve significant model outcomes, representing varying degrees of mild suppression of Ae. aegypti in a complex urban setting. In Addition, male handling, chilling, and transport emphasize the need to reduce the exposure to these parameters by improving the protocols. These results highlight key areas for scaling SIT within integrated vector management strategies in tropical urban settings.
Mapping Gene Drive Dynamics onto Mendelian Models
35414Zihang Wen, Monica Wan, Gili Greenbaum, Oana Carja, bioRxiv, 2026-01-30 16:46:40.
CRISPR-based gene drives bias their own transmission and can spread even when deleterious, giving rise to evolutionary dynamics that can be substantially more complex than those governed by standard Mendelian inheritance. Identifying conditions under which gene-drive dynamics can be faithfully approximated by Mendelian models would therefore enable the extensive theoretical toolkit of classical population genetics to be applied to gene-drive systems. Here, we develop a general mapping framework that translates gene-drive models into dynamically equivalent Mendelian models, allowing their behavior to be analyzed using classical theory. By deriving both haploid and diploid effective-parameter mappings, we identify Mendelian models that closely reproduce allele-frequency trajectories of gene drives across a wide range of conversion rates, fitness costs, and dominance effects. We delineate the regions of the parameter space where a one-parameter haploid approximation provides an accurate first-order representation, and where incorporating dominance in a diploid mapping substantially improves fidelity and recovers internal equilibria and threshold behavior. Analytic approximations yield efficient mappings across most of the drive parameter space, while a trajectory-based grid search further improves accuracy near nonlinear regime boundaries. To demonstrate the utility of this framework, we apply it to predicting gene swamping in a two-deme migration-selection model and show that the mapped Mendelian system accurately forecasts transitions between fixation and loss under three relevant release scenarios: environmental variation in fitness, engineered fitness asymmetries, and environment-dependent conversion. Together, these results establish a theoretical bridge between non-Mendelian gene drives and classical population genetic models, providing an interpretable and computationally efficient foundation for predicting gene-drive outcomes and guiding the design of gene drive systems and deployment strategies.
Assessing the population genetic structure and demographic history of Anopheles gambiae and Anopheles arabiensis at island and mainland sites in Uganda: implications for testing novel malaria vector control approaches
35384Mwima, R., Hui, TY.J., Lukyamuzi, E. et al., Malar J, 2026-01-20 13:40:12.
Despite substantial investments in malaria control, the disease remains a major burden in sub-Saharan Africa, particularly Uganda. Novel tools such as gene drive systems are being developed to suppress malaria vector populations, but their deployment requires detailed knowledge of mosquito population genetics. The genetic structure, diversity, and demographic history of Anopheles gambiae and Anopheles arabiensis were assessed at six sites in Uganda: three islands in Lake Victoria and three mainland sites. A total of 2918 An, gambiae and 173 An. arabiensis were genotyped using targeted amplicon sequencing of 62 loci across coding and non-coding regions of the genome. Population structure analyses revealed clear separation between the two species but little differentiation within each species across sites. Pairwise FST values among An. gambiae populations were low (0.00054–0.028) but often statistically significant, with mainland populations showing higher connectivity and island populations exhibiting greater isolation. Anopheles arabiensis mainland populations showed no statistically significant differentiation, suggesting panmixia. Principal component analysis and Bayesian clustering similarly distinguished species-level structure but no obvious substructure within sites. Mainland An. gambiae populations displayed higher nucleotide diversity than island populations, while An. arabiensis showed the lowest diversity overall. Tajima’s D values were negative across sites, consistent with recent population expansions. Effective population size estimates indicated small populations at the islands (146–249) compared to large mainland populations (4054–8190). These findings demonstrate strong genetic differentiation between An. gambiae and An. arabiensis, and subtle but meaningful structure between island and mainland An. gambiae populations. The reduced diversity and small effective population sizes at island sites suggest stronger genetic drift and limited gene flow, in contrast to the highly connected mainland populations. This study highlights how geographic and ecological factors shape mosquito population structure and provides critical evidence for the design and monitoring of genetic-based vector control interventions, including the planning and evaluation of field trials.
Beyond the static lab: environmental variability in genetically modified mosquito target gene identification for malaria control
35371Luna Dael, Maria L. Simões, Current Opinion in Insect Science, 2026-01-17 15:23:28.
As malaria remains a critical public health challenge causing hundreds of thousands of deaths annually, novel methods to combat it are urgently needed. Genetically modified mosquitoes (GMMs) offer a promising innovative approach to reduce malaria transmission. However, the foundational research to identify the target gene candidates for genetic modification is typically conducted under static laboratory conditions. These standardized insectary settings of constant temperature and humidity do not reflect the dynamic environmental and climatic variability that mosquitoes and the pathogens they carry encounter in nature. This review argues that this “lab-to-field” discrepancy represents a significant knowledge gap. We highlight that natural variations in environmental factors influence Anopheles and Plasmodium biology, and mosquito innate immunity responses, with consequences for vector competence and malaria transmission. Insufficient consideration of environmental variability during the initial gene discovery phase risks developing GMMs where the intended function of the genetic modification may be compromised by environmental stress. We emphasize the need to incorporate realistic environmental variability into the upstream GMM development, particularly in the face of escalating climate change.
Analysis of a household-scale model for the invasion of Wolbachia into a resident mosquito population
35327Barlow, A., Penington, S. & Adams, B., Journal of Mathematical Biology, 92. 2025-12-22 12:18:25.
In areas infested with Aedes aegypti mosquitoes it may be possible to control dengue, and some other vector-borne diseases, by introducing Wolbachia-infected mosquitoes into the wildtype population. Thus far, empirical and theoretical studies of Wolbachia release have tended to focus on the dynamics at the community scale. However, Ae. aegypti mosquitoes typically dwell in and around the same houses as the people they bite and it can be insightful to explore what happens at the household scale where small population sizes lead to inherently stochastic dynamics. Here we use a continuous-time Markov framework to develop a stochastic household model for small populations of wildtype and Wolbachia-infected mosquitoes. We investigate the transient and long term dynamics of the system, in particular examining the impact of stochasticity on the Wolbachia invasion threshold and bistability between the wildtype-only and Wolbachia-only steady states previously observed in deterministic models. We focus on the influence of key parameters which determine the fitness cost of Wolbachia infection and the probability of Wolbachia vertical transmission. Using Markov and matrix population theory, we derive salient characteristics of the system including the probability of successful Wolbachia invasion, the expected time until invasion and the probability that a Wolbachia-infected population reverts to a wildtype population. These attributes can inform strategies for the release of Wolbachia-infected mosquitoes. In addition, we find that releasing the minimum number of Wolbachia-infected mosquitoes required to displace a resident wildtype population according to the deterministic model, only results in that outcome about 20% of the time in the stochastic model; a significantly larger release is required to reach a steady state composed entirely of Wolbachia-infected mosquitoes 90% of the time.
Experimental demonstration of daisy chain gene drive and modelling of daisy suppression systems
35147Jialiang Guo, Weizhe Chen, Jackson Champer, bioRxiv, 2025-09-22 10:06:58.
CRISPR-based gene drive can address ecological problems by biased inheritance coupled with an effector for either population modification of suppression. However, the potential risk of uncontrolled spread impedes some applications of gene drive. Daisy chain gene drives have received much attention as a potential approach to overcome this problem. They potentially allow the efficient spread of drive elements in a target population, but are ultimately self-limiting. This is achieved by splitting a normal gene drive system into multiple dependent drive elements, where each element can bias the inheritance of another, except one non-driving element. With the successive loss of each chain link, the spread of transgenic elements will slow down and eventually stop. Here, we use modelling to assess the population dynamics of daisy chain drives in both panmictic and continuous space models, focusing on suppression systems. We find that achieving population elimination through a single release of daisy chain gene drives is possible but difficult, with relatively high requirements for drive performance and release size. These effects are substantially amplified in spatial models. We also constructed two configurations of daisy chain gene drives in Drosophila melanogaster as a proof-of-principle. One is a rescue drive for population modification, and the other aims for population suppression by targeting a haplosufficient female fertility gene. These drives all functioned within expectations at moderate efficiency in individual crosses. However, the drive design failed to spread in cage populations because of higher than expected fitness costs. Overall, our study demonstrates that daisy chain systems may be promising candidates for both modification and suppression, but challenges remain in both construction and potential deployment in large regions.
Natural Selection of Synthetic Gene Drives for Population Suppression Can Favor an Intermediate Strength of Drive
35141P. J. Beaghton and Austin Burt, The American Naturalist, 206. 2025-09-16 15:55:03.
Synthetic gene drives are being investigated as tools to suppress pest populations, and it is important to understand how natural selection will act on variant drivers that may either arise by de novo mutation or be intentionally released. In this study, we extend previous spatially implicit stochastic models to examine the evolutionary dynamics of synthetic driving Y chromosomes in patchy environments when population size is responding dynamically to the spread of the driver and derive conditions for the existence of an evolutionarily stable strategy (ESS) for drive strength. Under broad conditions, an intermediate drive strength emerges as the ESS, capable of outcompeting both stronger and weaker variants. Additionally, we show how the intentional release of two drivers straddling the ESS can help stabilize population dynamics. Finally, inbreeding depression has the effect of expanding the range of conditions under which no intermediate ESS exists, with ever stronger drive being selected until the population is eliminated. These results provide insights into the expected evolutionary trajectories of gene drive systems, with important implications for the design and release of gene drives for pest and vector control.
How population control of pests is modulated by density dependence: The perspective of genetic biocontrol
34993Cole D. Butler, Alun L. Lloyd, Journal of Theoretical Biology, 2025-07-30 11:07:06.
Managing pest species relies critically on mechanisms that regulate population dynamics, particularly those factors that change with population size. These density-dependent factors can help or hinder control efforts and are especially relevant considering recent advances in genetic techniques that allow for precise manipulation of the timing and sex-specificity of population suppression. Despite this importance, density dependence is often poorly characterized owing to limited data and an incomplete understanding of developmental ecology. To address this issue, we construct and analyze a mathematical model of a pest population with a general control under a wide range of density dependence scenarios. Using this model, we investigate how control performance is affected by the strength of density dependence. By modifying the timing and sex-specificity of the control, we tailor our analysis to simulate different pest control strategies, including conventional and genetic biocontrol methods. We pay particular attention to the latter as case studies by extending the baseline model to include genetic dynamics. Finally, we clarify past work on the dynamics of mechanistic models with density dependence. We find substantial differences in control performance for differing strengths of density dependence, with populations exhibiting strong density dependence being most resilient to suppression. However, these results change with the size and timing of the control load, as well as the target sex. Interestingly, we also find that the strength of density dependence affects population invasion by certain genetic biocontrol strategies. While the model is parameterized using the life history traits of the yellow fever mosquito, Aedes aegypti, the principles developed here apply to many pest species. We conclude by discussing what this means for pest population suppression moving forward.
Driving a protective allele of the mosquito FREP1 gene to combat malaria
34980Li, Z., Dong, Y., You, L. et al., Nature, 2025-07-24 09:46:46.
Malaria remains a substantial global health challenge, causing approximately half a million deaths each year1. The mosquito fibrinogen-related protein 1 (FREP1) is required for malaria parasites to infect the midgut epithelium2. The naturally occurring FREP1Q allele has been reported to prevent parasite infection, while supporting essential physiological functions in the mosquito3. Here we generate congenic strains of Anopheles stephensi, edited to carry either the parasite-susceptible FREP1L224 or the putative-refractory FREP1Q224 alleles. The FREP1Q224 allele confers robust resistance to infection by both human and rodent malaria parasites, with negligible fitness costs. The protective FREP1Q224 allele can be efficiently driven into FREP1L224 mosquito populations using a novel linked allelic-drive system that selectively replaces the L224 codon with the parasite-refractory Q224 allele, thereby rendering populations refractory to parasite infection. This antimalaria drive system provides a novel genetic approach to aid in malaria elimination efforts.
Mathematically modelling the population dynamics of CRISPR gene drive systems in the pine pest Sirex noctilio
34779Strydom, H., Ouifki, R., Chapwanya, M., bioRxiv, 2025-04-18 10:34:17.
Sirex noctilio is an invasive pest of pine that has caused significant economic damage in South Africa and many other Southern Hemisphere countries. Current management tools are not efficient in all cases and consequently there is a need for more efficient and targeted control measures. An emerging tool for pest management is the use of gene editing and associated gene drive systems. In this study, we aim to investigate the use of CRISPR-Cas gene drive systems in the management of S. noctilio in South Africa. As a first step, we developed a model for the population dynamics of S. noctilio, using historical national population monitoring data and incorporating the influence of two main biological control agents of the pest. We then modelled the influence of two different CRISPR-Cas systems on the population dynamics of S. noctilio namely, a baseline CRISPR model and Complementary Sex Determination CRISPR (CSD) model. Each model is used to simulate a male and female only introduction strategy to estimate the effectiveness of different methods of introducing the gene drive system. The model calibration was achieved by optimizing the model fit to existing data using the least squares technique. Results suggest that both CRISPR gene drive systems would be effective at controlling the population growth of S. noctilio at high levels of introduction, but overall population control would be hindered by practical limitations. Although only two CRISPR models were explored, the underlying population model serves as a framework for further studies into the population dynamics of Sirex noctilio, as well as many other CRISPR-Cas gene drive systems.
Evolutionary consequences of long-distance dispersal in mosquitoes
34776Thomas L Schmidt, Current Opinion in Insect Science, 68. 2025-04-18 10:25:09.
Long-distance dispersal (LDD) provides a means for mosquitoes to invade new regions and spread adaptive alleles, including those conferring insecticide resistance. Most LDD takes place on human transport vessels and will typically be rarer and more directionally constrained than active flight but can connect populations and regions that are otherwise mutually inaccessible. These features make LDD worthy of specific consideration in mosquito research. This paper reviews recent evolutionary research on LDD and its consequences for mosquito populations and mosquito control. LDD is the main source of mosquito range expansions, and genomic methods can now trace the origins of new invasions to specific towns or cities. Genomic methods can also give a rough indication of the number of invaders, which if very small may lead to the stochastic loss of advantageous alleles during invasion bottlenecks. Once invasions are established, LDD spreads adaptive alleles between populations. Emerging insights into insecticide resistance evolution indicate that LDD has repeatedly spread resistance mutations across global species ranges, but these broad patterns are convoluted by two other evolutionary processes: parallel adaptation at the same gene or gene cluster and polygenic adaptation at different genes in different populations. Together, these processes have produced patterns of similarity and dissimilarity at resistance genes that are decoupled from geographical distance. LDD within cities is less well studied but is important for planning and evaluating local control efforts. Urban investigations of LDD may help identify areas experiencing weaker selection pressures from insecticides and isolated areas to target for control.
Applications and status of gene drive in plants
34771Hay BA, PLOS Biology, 23. 2025-04-18 10:06:07.
Globalization—the movement of humans, plants, animals, and microbes—together with climate change, place numerous plant and animal species under novel stresses. For plants, threats include global warming, invasive species, weeds, animal pests, and vectors of disease. Harms can be mitigated or prevented through population-scale genetic alterations that introduce beneficial traits such as disease resistance or drought tolerance (population modification), or that eliminate a harmful population (population suppression). Gene drive is a possible tool for achieving these goals. DNA mediating gene drive comprises one or more genes (the drive element) that promote their own inheritance—and any linked cargo—at rates exceeding (>50%) those of other genes. This can lead to an increase in drive element frequency even if its presence results in a fitness cost to carriers. Gene drive is attractive because it is self-amplifying and self-sustaining. One class of gene drive utilizes a Toxin-Antidote (TA) element. In nature, these often consist of two tightly linked protein-encoding genes. One encodes a toxin that is inherited by all gametes and/or progeny of a carrier; the second is an antidote that protects carriers from death. The TA element-bearing chromosome gains a relative transmission advantage by causing death of those who fail to inherit it. The first synthetic gene drive was engineered using TA logic, in Drosophila melanogaster in 2007. Recently, TA logic was also used to create the first synthetic gene drive elements in plants, in Arabidopsis thaliana. These use a Cleave and Rescue mechanism (ClvR) adapted from earlier work in Drosophila. ClvR uses DNA cleavage mediated by Cas9 and guide RNAs (gRNAs), followed by inaccurate repair, to create loss-of-function (LOF) alleles (the toxin) of endogenous versions of an essential gene. ClvR also includes a Rescue version of the essential gene recoded to prevent gene disruption (the antidote), which guarantees survival of carriers. In Drosophila, ClvR spreads because LOF alleles created in parents cause the death of progeny who lack essential gene function. In Arabidopsis this strategy was used to create gamete killers. A naturally occurring male gamete killer from rice, DUYAO-JIEYAO, consists of a two-gene protein–protein TA cassette. Modeling suggests that gamete killers such as these can bring about population modification or suppression. Interestingly, the DUYAO-JIEYAO element has undergone a substantial increase in frequency in Japonica rice populations in China over the last 50 years, demonstrating the power of such elements in nature.
Escalation of genome defense capacity enables control of an expanding meiotic driver
34251P. Chen, K.C. Pan, E.H. Park, et al., Proceedings of the National Academy of Sciences, 122. 2025-01-13 15:02:27.
From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases. Such a binary architecture allows the defense systems to be readily adaptable, where new targets can be captured via innovation of specificity factors. Thus, our current understanding of genome defense against lineage-specific selfish genes has been largely limited to specificity factor innovations, while it remains poorly understood whether other types of innovations are required. Here, we describe a new type of innovation, which escalates the genome defense capacity to control a recently expanded selfish gene in Drosophila melanogaster. Through a targeted RNAi screen for repressors of Stellate—a recently evolved meiotic driver—we identified a defense factor, Trailblazer. Trailblazer is a transcription factor that promotes the expression of two PIWI-clade nucleases, Aub and AGO3, to match Stellate in abundance. Recent innovation in the DNA-binding domain of Trailblazer enabled it to elevate Aub and AGO3 expression, thereby escalating the silencing capacity of piRNA pathway to tame expanded Stellate and safeguard fertility. As copy-number expansion is a recurrent feature of diverse selfish genes across the tree of life, we envision that augmenting the defense capacity to quantitatively match selfish genes is a repeatedly employed defense strategy in evolution.
Parental-effect gene-drive elements under partial selfing, or why do Caenorhabditis genomes have hyperdivergent regions?
33170Matthew V Rockman, Genetics, 2024-10-31 08:57:53.
Self-fertile Caenorhabditis nematodes carry a surprising number of Medea elements, alleles that act in heterozygous mothers and cause death or developmental delay in offspring that don’t inherit them. At some loci, both alleles in a cross operate as independent Medeas, affecting all the homozygous progeny of a selfing heterozygote. The genomic coincidence of Medea elements and ancient, deeply coalescing haplotypes, which pepper the otherwise homogeneous genomes of these animals, raises questions about how these apparent gene-drive elements persist for long periods of time. Here I investigate how mating system affects the evolution of Medeas, and their paternal-effect counterparts, peels. Despite an intuition that antagonistic alleles should induce balancing selection by killing homozygotes, models show that, under partial selfing, antagonistic elements experience positive frequency dependence: the common allele drives the rare one extinct, even if the rare one is more penetrant. Analytical results for the threshold frequency required for one allele to invade a population show that a very weakly penetrant allele, one whose effects would escape laboratory detection, could nevertheless prevent a much more penetrant allele from invading under high rates of selfing. Ubiquitous weak antagonistic Medeas and peels could then act as localized barriers to gene flow between populations, generating genomic islands of deep coalescence. Analysis of gene expression data, however, suggest that this cannot be the whole story. A complementary explanation is that ordinary ecological balancing selection generates ancient haplotypes on which Medeas can evolve, while high homozygosity in these selfers minimizes the role of gene drive in their evolution.
Identification of novel genes responsible for a pollen killer present in local natural populations of Arabidopsis thaliana
32527Anthony Ricou, Matthieu Simon, et al., bioRxiv, 2024-10-15 11:51:17.
Certain genetic elements are qualified as selfish because they favor their transmission to the progeny during reproduction to the detriment of gametes that do not carry them. These elements are widespread in fungi as well as in plants or in animals, and they are made up of two or even three components, which are specific to each species. Therefore, they must be studied on a case-by-case basis. Moreover, understanding how they appear and propagate in local population remains a major issue in evolutionary biology. Here we have characterized, in the model plant Arabidopsis, the three genes involved in such an element, called a pollen killer. This pollen killer targets the mitochondria to cause the death of pollen grains that do not carry it. We investigated the three genes in several hundred genotypes collected worldwide, giving us a global view of their diversity at the species level. We also found that some French local populations contain both sensitive and killer plants, which constitutes an invaluable resource for studying the evolution of a pollen killer in the wild.
Understanding gene flow and its implications for gene drive research
31547Outreach Network for Gene Drive Research, 2024-09-16 09:02:52.
Gene flow is the transfer of genetic information from one population to another. Also known as gene transfer or gene migration, it plays a crucial role in the evolution and adaptation of species. Understanding the dynamics of gene flow is essential to assess the potential risks and benefits of gene drive approaches. Gene drive technology works by promoting the inheritance of a selected genetic trait within a population, leading to this trait becoming increasingly common within a specific species over time. Researchers have been studying how to harness this technology to address global challenges, including to control the transmission of vector-borne diseases and populations of invasive alien species which threaten sensitive ecosystems. Gene flow occurs naturally in the environment through two main dynamics: Vertical gene flow happens through mating, transferring genetic traits from one generation to another within a species or between closely related species. It is a natural part of evolutionary processes and plays a significant role in how traits are inherited. Horizontal gene flow involves the transfer of genes through non-sexual routes to unrelated organisms. While more common in bacteria, this type of gene flow is much less frequent in complex organisms. The potential implications of gene flow for gene drive research vary depending on specific circumstances. For example, gene drives could spread beneficial traits to malaria-carrying mosquitoes to help combat the disease. However, researchers must also consider whether the genetic modification could be passed on beyond its target population and, if so, whether it could lead to unintended impacts. Current studies indicate that gene flow between targeted and non-target species is generally unlikely due to genetic and ecological barriers. Despite this low probability, researchers continue to explore and refine gene drive technologies, notably by developing systems with built-in safeguards. These strategies aim to control how far and fast gene drives can spread by designing systems that only activate under specific conditions or within certain populations, or are self-limiting through time.
Population dynamics in spatial suppression gene drive models and the effect of resistance, density dependence, and life history
31190Xinyue Zhang, Weitang Sun, Isabel K. Kim, Philipp W. Messer, Jackson Champer, bioRxiv, 2024-08-27 08:13:04.
Due to their super-Mendelian inheritance, gene drive systems have the potential to provide revolutionary solutions to critical public health and environmental problems. For suppression drives, however, spatial structure can cause “chasing” population dynamics that may postpone target population elimination or even cause the drive to fail. In chasing, wild-type individuals elude the drive and recolonize previously suppressed areas. The drive can re-enter these recolonized areas, but often is not able to catch up to wild-type and finally eliminate it. Previous methods for chasing detection are only suitable to limited parameter ranges. In this study with expanded parameter ranges, we found that the shift from chasing dynamics to static equilibrium outcomes is continuous as drive performance is reduced. To quantify this, we defined a Weighted Average Nearest Neighbor statistic to assess the clustering degree during chasing, while also characterizing chasing by the per-generation chance of population elimination and drive loss. To detect chasing dynamics in local areas and to detect the start of chasing, we implemented Density-Based Spatial Clustering of Applications with Noise. Using these techniques, we determined the effect of arena size, resistance allele formation rate in both the germline and in the early embryo from maternally deposited Cas9, life history and reproduction strategies, and density-dependent growth curve shape on chasing outcomes. We found that larger real-world areas will be much more vulnerable to chasing and that species with overlapping generations, fecundity-based density dependence, and concave density-dependent growth curves have smaller and more clustered local chasing with a greater chance of eventual population elimination. We also found that embryo resistance and germline resistance hinder drive performance in different ways. These considerations will be important for determining the necessary drive performance parameters needed for success in different species, and whether future drives could potentially be considered as release candidates.
Wolbachia symbionts control sex in a parasitoid wasp using a horizontally acquired gene
29885Li C, Li CQ, Chen ZB, Liu BQ, Sun X, Wei KH, Li CY, Luan JB., Current Biology, 2024-05-07 15:55:59.
Host reproduction can be manipulated by bacterial symbionts in various ways. Parthenogenesis induction is the most effective type of reproduction manipulation by symbionts for their transmission. Insect sex is determined by regulation of doublesex (dsx) splicing through transformer2 (tra2) and transformer (tra) interaction. Although parthenogenesis induction by symbionts has been studied since the 1970s, its underlying molecular mechanism is unknown. Here we identify a Wolbachia parthenogenesis-induction feminization factor gene (piff) that targets sex-determining genes and causes female-producing parthenogenesis in the haplodiploid parasitoid Encarsia formosa. We found that Wolbachia elimination repressed expression of female-specific dsx and enhanced expression of male-specific dsx, which led to the production of wasp haploid male offspring. Furthermore, we found that E. formosa tra is truncated and non-functional, and Wolbachia has a functional tra homolog, termed piff, with an insect origin. Wolbachia PIFF can colocalize and interact with wasp TRA2. Moreover, Wolbachia piff has coordinated expression with tra2 and dsx of E. formosa. Our results demonstrate the bacterial symbiont Wolbachia has acquired an insect gene to manipulate the host sex determination cascade and induce parthenogenesis in wasps. This study reveals insect-to-bacteria horizontal gene transfer drives the evolution of animal sex determination systems, elucidating a striking mechanism of insect-microbe symbiosis.
Comparing the long-term persistence of different Wolbachia strains after the release of bacteria-carrying mosquitoes
29563Jose L. Orozco-Gonzales, Antone dos Santos Benedito, Daiver Cardona-Salgado et al., Mathematical Biosciences, 372. 2024-04-25 17:59:21.
This paper proposes a bidimensional modeling framework for Wolbachia invasion, assuming imperfect maternal transmission, incomplete cytoplasmic incompatibility, and direct infection loss due to thermal stress. Our model adapts to various Wolbachia strains and retains all properties of higher-dimensional models. The conditions for the durable coexistence of Wolbachia-carrying and wild mosquitoes are expressed using the model’s parameters in a compact closed form. When the Wolbachia bacterium is locally established, the size of the remanent wild population can be assessed by a direct formula derived from the model. The model was tested for four Wolbachia strains undergoing laboratory and field trials to control mosquito-borne diseases: wMel, wMelPop, wAlbB, and wAu. As all these bacterial strains affect the individual fitness of mosquito hosts differently and exhibit different levels of resistance to temperature variations, the model helped to conclude that: (1) the wMel strain spreads faster in wild mosquito populations; (2) the wMelPop exhibits lower resilience but also guarantees the smallest size of the remanent wild population; (3) the wAlbB strain performs better at higher ambient temperatures than others; (4) the wAu strain is not sustainable and cannot persist in the wild mosquito population despite its resistance to high temperatures.
Meeting Abstracts from the 5th B Chromosome Conference
28643Anonymous, BMC Proceedings, 17. 2023-12-05 09:57:11.
During preparations for the 5th B-Chromosome Conference (5BCC), rapid and significant progress was observed in the germ-restricted chromosomes (GRCs) study. GRCs are additional chromosomes found only in germ cells and are eliminated from somatic cells in many avian and dipteran species. Despite their specificity, GRCs share many features of B chromosomes. In view of this intriguing connection, we have decided to extend a special invitation to researchers dedicated to this fascinating topic and to encourage them to participate in the 5BCC. The 5th B Chromosome Conference will be held in Petnica, Serbia, from 14th to 17th October 2023. The conference will take place in five sessions: Constitution, gene composition, Dynamics in populations, B chromosome effects, Segregation behaviour, Origin and evolution. The conference will unite the most prominent chromosome biologists for a stimulating exchange of ideas and insights. We hope that the conference will help establish better collaboration and enable progress in B chromosome research.
Anopheles gambiae on remote islands in the Indian Ocean: origins and prospects for malaria elimination by genetic modification of extant populations
28597Ditter, R.E., Campos, M., Crepeau, M.W. et al., Scientific Reports, 13. 2023-11-29 16:40:50.
The mosquito Anopheles gambiae s.s. is a primary malaria vector throughout sub-Saharan Africa including the islands of the Comoros archipelago (Anjouan, Grande Comore, Mayotte and Mohéli). These islands are located at the northern end of the Mozambique Channel in eastern Africa. Previous studies have shown a relatively high degree of genetic isolation between the Comoros islands and mainland populations of A. gambiae, but the origin of the island populations remains unclear. Here, we analyzed phylogenetic relationships among island and mainland populations using complete mitochondrial genome sequences of individual A. gambiae specimens. This work augments earlier studies based on analysis of the nuclear genome. We investigated the source population of A. gambiae for each island, estimated the number of introductions, when they occurred and explored evidence for contemporary gene flow between island and mainland populations. These studies are relevant to understanding historical patterns in the dispersal of this important malaria vector and provide information critical to assessing their potential for the exploration of genetic-based vector control methods to eliminate this disease. Phylogenetic analysis and haplotype networks were constructed from mitogenome sequences of 258 A. gambiae from the four islands. In addition, 112 individuals from seven countries across sub-Saharan Africa and Madagascar were included to identify potential source populations. Our results suggest that introduction events of A. gambiae into the Comoros archipelago were rare and recent events and support earlier claims that gene flow between the mainland and these islands is limited. This study is concordant with earlier work suggesting the suitability of these oceanic islands as appropriate sites for conducting field trial releases of genetically engineered mosquitoes (GEMs).
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.
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.
Routes of Introduction of Anopheles gambiae Into Remote Islands in the Indian Ocean
26612R. E. Ditter, M. Campos, M. W. Crepeau, J. Pinto, A. Toilibou, Y. Amina, Y. Lee, A. J. Cornel and G. C. Lanzaro, 2023-07-07 13:23:28.
The malaria vector Anopheles gambiae s.s., is a primary malaria vector throughout sub-Saharan Africa including the islands of the Comoros archipelago (Anjouan, Grande Comore, Mayotte and Mohéli). These islands are located at the northern end of the Mozambique Channel in eastern Africa. Previous studies have shown a relatively high degree of genetic isolation between island and mainland populations of A. gambiae, but the origin of the island populations remains unclear. Here, we analyzed phylogenetic relationships among island and mainland populations using complete mitochondrial genome sequences of individual A. gambiae specimens. We investigated the source population of A. gambiaefor each island, determined the number of introductions and estimated when they occurred, and explored evidence for contemporary gene flow between island and mainland populations. Phylogenetic analysis and haplotype networks were constructed from mitogenome sequences of 258 A. gambiae from the four islands. In addition, 112 individuals from seven countries across sub-Saharan Africa and Madagascar were included to identify potential source populations. Our results suggest that introduction events of A. gambiae into the Comoros archipelago were rare and recent events and that there is no evidence of contemporary migration between the islands and mainland Africa. This study further supports the suitability of these oceanic islands as appropriate sites for conducting field trial releases of genetically engineered mosquitoes (GEMs).
Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages
25086A. Simoni, R. D'Amato, C. Taxiarchi, M. Galardini, A. Trusso, R. Minuz, S. Gilli, A. Somerville, D. Shittu, A. Khalil, R. Galizi and R. Muller, Research Square, 2023-04-24 06:46:30.
CRISPR-based gene drives have the potential to spread within a population and are considered as promising vector control tools. A doublesex-targeting gene drive was shown effective to suppress laboratory populations in both small and large cages, and it is considered for field application. Challenges related to the field-use of gene drives and the evolving regulatory framework demand for systems able to modulate or revert the action of gene drives, as part of post-release risk-mitigation plans. We developed an improved AcrIIA4-based anti-drive strain and showed inhibition of gene drive spread, in complex feeding and reproductive behavioural conditions. A stochastic model predicted the experimentally-observed genotypes dynamics in overlapping generations in medium- and large-sized cages and further demonstrated the effectiveness of anti-drive in different release and fitness scenarios. This study provides a further validation for the use of anti-drive system in controlling the spread of gene drive in Anopheles under complex behavioural conditions.
Synthetic gene drives as an anthropogenic evolutionary force
24895A. D. Cutter, Trends in Genetics, 2023-03-28 07:24:22.
Genetic drive represents a fundamental evolutionary force that can exact profound change to the genetic composition of populations by biasing allele transmission. Herein I propose that the use of synthetic homing gene drives, the human-mediated analog of endogenous genetic drives, warrants the designation of ‘genetic welding’ as an anthropogenic evolutionary force. Conceptually, this distinction parallels that of artificial and natural selection. Genetic welding is capable of imposing complex and rapid heritable phenotypic change on entire populations, whether motivated by biodiversity conservation or public health. Unanticipated possible long-term evolutionary outcomes, however, demand further investigation and bioethical consideration. The emerging importance of genetic welding also compels our explicit recognition of genetic drive as an addition to the other four fundamental forces of evolution.
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.
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.
The effect of mating complexity on gene drive dynamics
23967P. Verma, R. G. Reeves, S. Simon, M. Otto and C. S. Gokhale, The American Naturalist, 2022-11-15 12:33:47.
Gene drive technology promises to deliver on some of the global challenges humanity faces today in health care, agriculture, and conservation. However, there is a limited understanding of the consequences of releasing self-perpetuating transgenic organisms into wild populations under complex ecological conditions. In this study, we analyze the impact of three such complexities—mate choice, mating systems, and spatial mating network—on the population dynamics for two distinct classes of modification gene drive systems. All three factors had a high impact on the modeling outcome. First, we demonstrate that distortion-based gene drives appear to be more robust against mate choice than viability-based gene drives. Second, we find that gene drive spread is much faster for higher degrees of polygamy. Including a fitness cost, the drive is fastest for intermediate levels of polygamy. Finally, the spread of a gene drive is faster and more effective when the individuals have fewer connections in a spatial mating network. Our results highlight the need to include mating complexities when modeling the properties of gene drives, such as release thresholds, timescales, and population-level consequences. This inclusion will enable a more confident prediction of the dynamics of engineered gene drives and possibly even inform about the origin and evolution of natural gene drives.
Rescue by gene swamping as a gene drive deployment strategy
20587K. D. Harris and G. Greenbaum, bioRxiv, 2022.03.08.483503. 2022-03-08 11:25:49.
Gene drives are genetic constructs that can spread deleterious alleles with potential application to population suppression of harmful species. Given that a gene drive can potentially spill over to other populations or even other species, control measures and fail-safes strategies must be considered. Gene drives are designed to generate a rapid demographic decline, while at the same time generating a dynamic change in the population’s genetics. Since these evolutionary and demographic processes are linked and are expected to occur at a similar time-scale during gene drive spread, feedback between these processes may significantly affect the outcome of deployment. To study this feedback and to understand how it affects gene drive spillovers, we developed a gene drive model that combines evolutionary and demographic dynamics in a two-population setting. The model demonstrates how feedback between evolutionary and demographic dynamics can generate additional outcomes to those generated by the evolutionary dynamics alone. We identify an outcome of particular interest, where the short-term suppression of the target population is followed by gene swamping and loss of the gene drive. This outcome could be useful for designing gene drive deployments that temporarily suppress the population, but ultimately do not remain in the population. Using our model, we demonstrate the robustness of this outcome to spillover and to the evolution of resistance, and suggest that it could be used as a fail-safe strategy for gene drive deployment.Competing Interest StatementThe authors have declared no competing interest.
Sterile males and females can synergistically suppress wild pests targeted by sterile insect technique
18837Y. Ikegawa, K. Ito, C. Himuro and A. Honma, Journal of Theoretical Biology, 530. 2021-08-23 11:21:38.
We constructed a mathematical model to examine the contribution of sterile males and females to the pest-control effect and the synergy between them. We consider that males seek out and court females in accord with their own female searching ability and preference, and that females subsequently choose one male from among males courting them in accordance with their own preference. Using this model, we compared the pest-control effect of bisexual and unisexual release, focusing on the difference in mating systems of the targeted insects. We showed that for swarm-type mating systems (with few courtship chances with higher encounter rates), bisexual release was the most effective, irrespective of the relative female searching ability between wild and sterile males. In this case, sterile females indirectly reduce wild females mating with either male by absorbing courtship from both wild and sterile males. By contrast, bisexual release is the most effective for scramble-type mating systems (more courtship chances with lower encounter rates) only when the female searching ability of sterile males is lower than that of wild males. In this case, sterile females absorb courtship from males with higher searching abilities. Therefore, the net impact of sterile females depends on the difference in sexual performance between wild and sterile males. Because the sexual performance of sterile insects is often degraded during the process of sterilization, we suggest that bisexual release can be a compatible measure to efficiently suppress wild pest populations.
Fine-scale estimation of key life-history parameters of malaria vectors: implications for next-generation vector control technologies
17329A. L. Morris, A. Ghani and N. Ferguson, Parasites and Vectors, 14:311. 2021-06-08 14:48:41.
Mosquito control has the potential to significantly reduce malaria burden on a region, but to influence public health policy must also show cost-effectiveness. Gaps in our knowledge of mosquito population dynamics mean that mathematical modelling of vector control interventions have typically made simplifying assumptions about key aspects of mosquito ecology. Often, these assumptions can distort the predicted efficacy of vector control, particularly next-generation tools such as gene drive, which are highly sensitive to local mosquito dynamics.
Invasion and maintenance of meiotic drivers in populations of ascomycete fungi
17071I. Martinossi-Allibert, C. Veller, S. L. Ament-Velasquez, A. A. Vogan, C. Rueffler and H. Johannesson, Evolution, 20. 2021-03-25 14:37:42.
Meiotic drivers (MDs) are selfish genetic elements that are able to become overrepresented among the products of meiosis. This transmission advantage makes it possible for them to spread in a population even when they impose fitness costs on their host organisms. Whether an MD can invade a population, and subsequently reach fixation or coexist in a stable polymorphism, depends on the one hand on the biology of the host organism, including its life cycle, mating system, and population structure, and on the other hand on the specific fitness effects of the driving allele on the host. Here, we present a population genetic model for spore killing, a type of drive specific to fungi. We show how ploidy level, rate of selfing, and efficiency of spore killing affect the invasion probability of a driving allele and the conditions for its stable coexistence with a nondriving allele. Our model can be adapted to different fungal life cycles, and is applied here to two well-studied genera of filamentous ascomycetes known to harbor spore-killing elements, Neurospora and Podospora. We discuss our results in the light of recent empirical findings for these two systems.
Demographic feedbacks can hamper the spatial spread of a gene drive
16203L. Girardin and F. Débarre, arXiv, 2021-01-27 15:32:53.
Our results indicate that taking into account the interplay between population dynamics and population genetics might actually be crucial, as it can effectively reverse the direction of the invasion and lead to failure. Our findings can be extended to other bistable systems, such as the spread of cytoplasmic incompatibilities caused by Wolbachia.
Selfing is the safest sex for Caenorhabditis tropicalis
15953L. M. Noble, J. Yuen, L. Stevens, N. D. Moya, R. Persaud, M. Moscatelli, J. L. Jackson, G. Zhang, R. Chitrakar, L. R. Baugh, C. Braendle, E. C. Andersen, H. S. Seidel and M. V. Rockman, eLife, 10:e62587. 2021-01-11 16:59:39.
We generated a chromosomal-scale genome for C. tropicalis and surveyed global diversity. Population structure is very strong, and islands of extreme divergence punctuate a genomic background that is highly homogeneous around the globe. Outbreeding depression in the laboratory is caused largely by multiple Medea-like elements, genetically consistent with maternal toxin/zygotic antidote systems. Loci with Medea activity harbor novel and duplicated genes, and their activity is modified by mito-nuclear background. Segregating Medea elements dramatically reduce fitness, and simulations show that selfing limits their spread. Frequent selfing in C. tropicalis may therefore be a strategy to avoid Medea-mediated outbreeding depression.
Mosquito Sexual Selection and Reproductive Control Programs
15921L. J. Cator, C. A. S. Wyer and L. C. Harrington, Trends in Parasitology, 2021-01-06 18:45:40.
Recent work has generated many key insights about specific aspects of mating behavior and physiology. Here, we synthesize these findings and classify swarming mosquito systems as polygynous. Male mating success is highly variable in swarms and evidence suggests that it is likely determined by both scramble competition between males and female choice. Incorporating this new understanding will improve both implementation and long-term stability of reproductive control tools.
Genetic pest management and the background genetics of release strains
15695P. T. Leftwich, L. G. Spurgin, T. Harvey-Samuel, C. J. E. Thomas, L. C. Paladino, M. P. Edgington and L. Alphey, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190805. 2020-12-28 15:35:20.
We discuss issues around strain selection and the potential consequences of such introgression. We conclude that such introgression is probably harmless in almost all circumstances, and could, in theory, provide specific additional benefits to the release programme. We outline population monitoring approaches that could be used, going forward, to determine how background genetics may affect GPM. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.
Wolbachia strain wAlbB maintains high density and dengue inhibition following introduction into a field population of Aedes aegypti
15689N. A. Ahmad, M.-V. Mancini, T. H. Ant, J. Martinez, G. M. R. Kamarul, W. A. Nazni, A. A. Hoffmann and S. P. Sinkins, Philosophical Transactions of the Royal Society B: Biological Sciences, 376:20190809. 2020-12-28 15:06:28.
Here, wAlbB-carrying Ae. aegypti collected from the field 20 months after the cessation of releases showed no reduction in Wolbachia density or tissue distribution changes compared to a wAlbB laboratory colony. The wAlbB strain continued to induce complete unidirectional cytoplasmic incompatibility, showed perfect maternal transmission under laboratory conditions, and retained its capacity to inhibit dengue. Additionally, a field-collected wAlbB line was challenged with Malaysian dengue patient blood, and showed significant blocking of virus dissemination to the salivary glands.
Polyandry blocks gene drive in a wild house mouse population
15390A. Manser, B. Konig and A. K. Lindholm, Nature Communications, 11:8. 2020-12-11 14:12:22.
Here, we study the impact of polyandry on a well-known gene drive, called t haplotype, in an intensively monitored population of wild house mice. First, we show that house mice are highly polyandrous: 47% of 682 litters were sired by more than one male. Second, we find that drive-carrying males are particularly compromised in sperm competition, resulting in reduced reproductive success. As a result, drive frequency decreased during the 4.5 year observation period. Overall, we provide the first direct evidence that the spread of a gene drive is hampered by reproductive behaviour in a natural population.
X-linked meiotic drive can boost population size and persistence
16876C. Mackintosh, A. Pomiankowski and M. F. Scott, Genetics, 217:11. 2020-12-10 14:26:46.
Here, we find general conditions for the spread and fixation of X-linked alleles. Our conditions show that the spread of X-linked alleles depends on sex-specific selection and transmission rather than the time spent in each sex. Applying this logic to meiotic drive, we show that polymorphism is heavily dependent on sperm competition induced both by female and male mating behavior and the degree of compensation to gamete loss in the ejaculate size of drive males. We extend these evolutionary models to investigate the demographic consequences of biased sex ratios. Our results suggest driving X-alleles that invade and reach polymorphism (or fix and do not bias segregation excessively) will boost population size and persistence time by increasing population productivity, demonstrating the potential for selfish genetic elements to move sex ratios closer to the population-level optimum. However, when the spread of drive causes strong sex-ratio bias, it can lead to populations with so few males that females remain unmated, cannot produce offspring, and go extinct. This outcome is exacerbated when the male mating rate is low. We suggest that researchers should consider the potential for ecologically beneficial side effects of selfish genetic elements, especially in light of proposals to use meiotic drive for biological control.
Selfish genetic elements and male fertility
15183R. L. Verspoor, T. A. R. Price and N. Wedell, Philosophical Transactions of the Royal Society B-Biological Sciences, 375:7. 2020-10-20 14:40:03.
Selfish genetic elements (SGEs) are diverse and near ubiquitous in Eukaryotes and can be potent drivers of evolution. Here, we discuss SGEs that specifically act on sperm to gain a transmission advantage to the next generation. The diverse SGEs that affect sperm often impose costs on carrier males, including damaging ejaculates, skewing offspring sex ratios and in particular reducing sperm-competitive success of SGE-carrying males. How males and females tolerate and mitigate against these costs is a dynamic and expanding area of research. The intense intra-genomic conflict that these selfish elements generate could also have implications for male fertility and spermatogenesis more widely. This article is part of the theme issue 'Fifty years of sperm competition'.
MGDrivE 2: A simulation framework for gene drive systems incorporating seasonality and epidemiological dynamics
14733S. L. Wu, J. B. Bennett, H. M. Sanchez C, A. J. Dolgert, T. M. Leon and J. M. Marshall, bioRxiv, 2020.10.16.343376. 2020-10-17 15:42:27.
We present MGDrivE 2 (Mosquito Gene Drive Explorer 2): an extension of and development from the MGDrivE 1 simulation framework that investigates the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations.
Embracing Dynamic Models for Gene Drive Management
14596A. J. Golnar, E. Ruell, A. L. Lloyd and K. M. Pepin, Trends in Biotechnology, 2020-09-30 13:54:04.
We describe how quantitative tools can reduce risk uncertainty, streamline empirical research, guide risk management, and promote cross-sector collaboration throughout the process of gene drive technology development and implementation.
Suppressing evolution in genetically engineered systems through repeated supplementation
15188N. C. Layman, B. M. Tuschhoff, A. J. Basinski, C. H. Remien, J. J. Bull and S. L. Nuismer, Evolutionary Applications, 12. 2020-09-05 15:21:40.
Genetically engineered organisms are prone to evolve in response to the engineering. This evolution is often undesirable and can negatively affect the purpose of the engineering. Methods that maintain the stability of engineered genomes are therefore critical to the successful design and use of genetically engineered organisms. One potential method to limit unwanted evolution is by taking advantage of the ability of gene flow to counter local adaption, a process of supplementation. Here, we investigate the feasibility of supplementation as a mechanism to offset the evolutionary degradation of a transgene in three model systems: a bioreactor, a gene drive, and a transmissible vaccine.
Lateral Gene Transfer Mechanisms and Pan-genomes in Eukaryotes
13939S. J. Sibbald, L. Eme, J. M. Archibald and A. J. Roger, Trends in Parasitology, 2020-08-19 17:12:29.
Here we review evidence for known and potential mechanisms of LGT into diverse eukaryote lineages with a particular focus on protists, and we discuss trends emerging from recently reported examples. We also explore the potential role of LGT in generating ‘pan-genomes’ in diverse eukaryotic species.
Invasion and maintenance of spore killers in populations of ascomycete fungi
15129I. Martinossi-Allibert, C. Veller, S. L. Ament-Velásquez, A. A. Vogan, C. Rueffler and H. Johannesson, bioRxiv, 2020.04.06.026989. 2020-06-30 16:08:48.
We show how ploidy level, rate of selfing, and efficiency of spore killing affect the invasion probability of a driving allele and the conditions for its stable coexistence with the non-driving allele. Our model can be adapted to different fungal life-cycles, and is applied here to two well-studied genera of filamentous ascomycetes known to harbor spore killing elements, Podospora and Neurospora. We discuss our results in the light of recent empirical findings for these two systems.Competing Interest StatementThe authors have declared no competing interest.
Case Study 1: Olive Fruit Fly (Bactrocera oleae)
11255Merle Preu, Johannes L. Frieß, Broder Breckling and Winfried Schröder, Gene Drives at Tipping Points, 2020-04-28 18:31:15.
The olive fruit fly Bactrocera oleae is a phytophagous insect associated to olive trees (Olea europaea, Oleaceae). Its larvae monophagously feed on olive fruits, the fly is therefore considered the most severe pest of olive cultivation causing tremendous economic losses. The olive fly therefore poses a good example of a potential target organism in a European context. This case study revealed that uncertainties exist with regard to the dispersal capacity of gene drive-bearing olive flies, as well as concerning the high gene flow between different populations and most importantly with regard to the population bottlenecks that regularly occur in winter. These would significantly increase or decrease genetic variability between subpopulations and thereby severely jeopardize the intended outcome of any SPAGE-application.
Selfish genes and sexual selection: the impact of genomic parasites on host reproduction
11970N. Wedell, Journal of Zoology, 311:1-12. 2020-04-08 18:18:42.
Selfish genetic elements (SGEs) such as replicating mobile elements, segregation distorters and maternally inherited endosymbionts, bias their transmission success relative to the rest of the genome to increase in representation in subsequent generations. As such, they generate conflict with the rest of the genome. Such intragenomic conflict is also a hallmark of sexually antagonistic (SA) alleles, which are shared genes between the sexes but that have opposing fitness effects when expressed in males and females. However, whilst both SGEs and SA alleles are recognized as common and potent sources of genomic conflict, the realization that SGEs can also generate sexually antagonistic selection and contribute to sexual conflict in addition to generate sexual selection is largely overlooked. Here, I show that SGEs frequently generate sex-specific selection and outline how SGEs that are associated with compromised male fertility can shape female mating patterns, play a key role in the dynamics of sex-determination systems and likely be an important source of sexually antagonistic genetic variation. Given the prevalence of SGEs, their contribution to sexual conflict is likely to be greatly overlooked.
Experimental manipulation of selfish genetic elements links genes to microbial community function
11218S. D. Quistad, G. Doulcier and P. B. Rainey, Philosophical Transactions of the Royal Society B-Biological Sciences, 375:12. 2020-03-23 15:17:13.
Microbial communities underpin the Earth's biological and geochemical processes, but their complexity hampers understanding. Motivated by the challenge of diversity and the need to forge ways of capturing dynamical behaviour connecting genes to function, biologically independent experimental communities comprising hundreds of microbial genera were established from garden compost and propagated on nitrogen-limited minimal medium with cellulose (paper) as sole carbon source. After 1 year of bi-weekly transfer, communities retained hundreds of genera. To connect genes to function, we used a simple experimental manipulation that involved the periodic collection of selfish genetic elements (SGEs) from separate communities, followed by pooling and redistribution across communities. The treatment was predicted to promote amplification and dissemination of SGEs and thus horizontal gene transfer. Confirmation came from comparative metagenomics, which showed the substantive movement of ecologically significant genes whose dynamic across space and time could be followed. Enrichment of genes implicated in nitrogen metabolism, and particularly ammonification, prompted biochemical assays that revealed a measurable impact on community function. Our simple experimental strategy offers a conceptually new approach for unravelling dynamical processes affecting microbial community function. This article is part of the theme issue 'Conceptual challenges in microbial community ecology'.
Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes
14309H. Schmidt, T. C. Collier, M. J. Hanemaaijer, P. D. Houston, Y. Lee and G. C. Lanzaro, Nature Communications, 11. 2020-03-16 12:39:04.
ere we report the results of a survey of 1280 genomes of the mosquitoes Anopheles gambiae, An. coluzzii, and Aedes aegypti in which we determine that similar to 90% of all protein-encoding CGD target genes in natural populations include at least one target site with no DRAs at a frequency of >= 1.0%.
Population-level multiplexing: A promising strategy to manage the evolution of resistance against gene drives targeting a neutral locus
11212M. P. Edgington, T. Harvey-Samuel and L. Alphey, Evolutionary Applications, 10. 2020-03-06 14:52:40.
CRISPR-based gene drives bias inheritance in their favour by inducing double-stranded breaks (DSBs) at wild-type homologous loci and using the drive transgene as a repair template-converting drive heterozygotes into homozygotes. Recent studies have shown that alternate end-joining repair mechanisms produce cut-resistant alleles that rapidly induce drive failure. Multiplexing-simultaneously targeting multiple sites at the wild-type locus-is commonly assumed to overcome this issue since resistance would need to develop at all target sites for the system to fail. This may work for some population suppression drives targeting essential (e.g. viability or fertility) genes if careful design can ensure cut-resistant alleles themselves have low fitness. However, here, models are used to demonstrate that this approach will be ineffective when targeting neutral loci. We then go on to compare the performance of four alternative population-level multiplexing approaches with standard individual-level multiplexing. Two of these approaches have mechanisms preventing them from becoming linked, thus avoiding multiple simultaneous DSBs and giving a large improvement. Releasing multiple unlinked drives gives a modest improvement, while releasing multiple drives that may become linked over time produces a decrease in performance under the conditions tested here. Based on performance and technical feasibility, we then take one approach forward for further investigation, demonstrating its robustness to different performance parameters and its potential for controlling very large target populations.
Optimal control and analysis of a modified trojan Y-Chromosome strategy
11491M. A. Beauregard, R. D. Parshad, S. Boon, H. Conaway, T. Griffin and J. J. Lyu, Ecological Modelling, 416. 2020-01-15 20:19:52.
The Trojan Y Chromosome (TYC) strategy is a promising eradication method that attempts to manipulate the female to male ratio to promote the reduction of the population of an invasive species. The manipulation stems from an introduction of sex-reversed males, called supermales, into an ecosystem. The offspring of the supermales is guaranteed to be male. Mathematical models have shown that the population can be driven to extinction with a continuous supply of supermales. In this paper, a new model of the TYC strategy is introduced and analyzed that includes two important modeling characteristics, that are neglected in all previous models. First, the new model includes intraspecies competition for mates. Second, a strong Allee effect is included. Several conclusions about the strategy via optimal control are established. These results have large scale implications for the biological control of invasive species.
Transcontinental dispersal of Anopheles gambiae occurred from West African origin via serial founder events
14311H. Schmidt, Y. Lee, T. C. Collier, M. J. Hanemaaijer, O. D. Kirstein, A. Ouledi, M. Muleba, D. E. Norris, M. Slatkin, A. J. Cornel and G. C. Lanzaro, Communications Biology, 2. 2019-12-19 12:47:18.
Here we present population genomic analyses of 111 specimens sampled from west to east Africa, including the first whole genome sequences from oceanic islands, the Comoros.
A selfish genetic element linked to increased lifespan impacts metabolism in female house mice
5652Lopes, P. C. and A. K. Lindholm, The Journal of Experimental Biology, 2019:212704. 2019-12-17 18:01:15.
Gene drive systems can lead to the evolution of traits that further enhance the transmission of the driving element. In gene drive, one allele is transmitted to offspring at a higher frequency than the homologous allele. This has a range of consequences, which generally include a reduction in fitness of the carrier of the driving allele, making such systems “selfish”. The t haplotype is one such driver, found in house mice. It is linked to a reduction in litter size in matings among heterozygous animals, but also to increased lifespan in wild females that carry it. Here, we tested whether carrying the t haplotype was associated with altered resting metabolic rate (RMR). We show that females carrying the t haplotype decrease RMR as they increase in size, compared to wildtype females or males of either genotype. Our study elucidates a plausible mechanism by which a selfish genetic element increases lifespan.
An X-linked meiotic drive allele has strong, recessive fitness costs in female Drosophila pseudoobscura
6171W. Larner, T. Price, L. Holman and N. Wedell, Proceedings of the Royal Society B-Biological Sciences, 286:9. 2019-11-27 18:44:20.
Selfish 'meiotic drive' alleles are transmitted to more than 50% of offspring, allowing them to rapidly invade populations even if they reduce the fitness of individuals carrying them. Theory predicts that drivers should either fix or go extinct, yet some drivers defy these predictions by persisting at low, stable frequencies for decades. One possible explanation for this discrepancy is that drivers are especially costly when homozygous, although empirical tests of this idea are rare and equivocal. Here, we measure the fitness of female Drosophila pseudoobscura carrying zero, one or two copies of the X-linked driver sex ratio (SR). SR had strong negative effects on female offspring production and the probability of reproductive failure, and these effects were largely similar across four genetic backgrounds. SR was especially costly when homozygous. We used our fitness measurements to parametrize a population genetic model, and found that the female fitness costs observed here can explain the puzzlingly low allele frequency of SR in nature. We also use the model to show how spatial variation in female mating behaviour, fitness costs of SR and the reduced siring success of SR males can jointly explain the north-south cline in SR frequencies across North America.
Effects of a male meiotic driver on male and female transcriptomes in the house mouse
6639A. Lindholm, A. Sutter, S. Kunzel, D. Tautz and H. Rehrauer, Proceedings of the Royal Society B-Biological Sciences, 286:1-8. 2019-11-13 20:18:05.
Not all genetic loci follow Mendel's rules, and the evolutionary consequences of this are not yet fully known. Genomic conflict involving multiple loci is a likely outcome, as restoration of Mendelian inheritance patterns will be selected for, and sexual conflict may also arise when sexes are differentially affected. Here, we investigate effects of the t haplotype, an autosomal male meiotic driver in house mice, on genome-wide gene expression patterns in males and females. We analysed gonads, liver and brain in adult same-sex sibling pairs differing in genotype, allowing us to identify t-associated differences in gene regulation. In testes, only 40% of differentially expressed genes mapped to the approximately 708 annotated genes comprising the t haplotype. Thus, much of the activity of the t haplotype occurs in trans, and as upregulation. Sperm maturation functions were enriched among both cis and trans acting t haplotype genes. Within the t haplotype, we observed more downregulation and differential exon usage. In ovaries, liver and brain, the majority of expression differences mapped to the t haplotype, and were largely independent of the differences seen in the testis. Overall, we found widespread transcriptional effects of this male meiotic driver in the house mouse genome.
Does meiotic drive alter male mate preference?
7960S. R. Finnegan, L. Nitsche, M. Mondani, M. F. Camus, K. Fowler and A. Pomiankowski, Behavioral Ecology, 13:194-201. 2019-10-20 14:14:20.
Male mate preferences have been demonstrated across a range of species, including the Malaysian stalk-eyed fly, Teleopsis dalmanni. This species is subject to sex-ratio (SR), an X-linked male meiotic driver, which causes the dysfunction of Y-sperm and the production of all-female broods. While there has been work considering female avoidance of meiotic drive males, the mating decisions of drive-bearing males have not been considered previously. Drive males may be less able to bear the cost of choice as SR is associated with a low-frequency inversion that causes reduced organismal fitness. Drive males may also experience weaker selection for preference maintenance if they are avoided by females. Using binary choice trials, across two experiments, we confirmed male preference for large (fecund) females but found no evidence that the strength of male preference differs between drive and standard males. We showed that large eyespan males displayed strong preference for large females, whereas small eyespan males showed no preference. Taken together, these results suggest that, even though meiotic drive is associated with lower genetic quality, it does not directly interfere with male mate preference among available females. However, as drive males tend to have smaller eyespan (albeit only similar to 5% on average), this will to a minor extent weaken their strength of preference.
Gene Drives: Dynamics and Regulatory Matters-A Report from the Workshop “Evaluation of Spatial and Temporal Control of Gene Drives,” April 4-5, 2019, Vienna
12396B. Giese, J. L. Friess, N. H. Barton, P. W. Messer, F. Debarre, M. F. Schetelig, N. Windbichler, H. Meimberg and C. Boete, Bioessays, 41:3. 2019-10-07 18:26:19.
Gene Drives are regarded as future tools with a high potential for population control. Due to their inherent ability to overcome the rules of Mendelian inheritance, gene drives (GD) may spread genes rapidly through populations of sexually reproducing organisms. A release of organisms carrying a GD would constitute a paradigm shift in the handling of genetically modified organisms because gene drive organisms (GDO) are designed to drive their transgenes into wild populations and thereby increase the number of GDOs. The rapid development in this field and its focus on wild populations demand a prospective risk assessment with a focus on exposure related aspects. Presently, it is unclear how adequate risk management could be guaranteed to limit the spread of GDs in time and space, in order to avoid potential adverse effects in socio‐ecological systems. The recent workshop on the “Evaluation of Spatial and Temporal Control of Gene Drives” hosted by the Institute of Safety/Security and Risk Sciences (ISR) in Vienna aimed at gaining some insight into the potential population dynamic behavior of GDs and appropriate measures of control. Scientists from France, Germany, England, and the USA discussed both topics in this meeting on April 4–5, 2019. This article summarizes results of the workshop.
A century of bias in genetics and evolution
6691L. D. Hurst, Heredity, 123:33-44. 2019-06-12 17:55:20.
Mendel proposed that the heritable material is particulate and that transmission of alleles is unbiased. An assumption of unbiased transmission was necessary to show how variation can be preserved in the absence of selection, so overturning an early objection to Darwinism. In the second half of the twentieth century, it was widely recognised that even strongly deleterious alleles can invade if they have strongly biased transmission (i.e. strong segregation distortion). The spread of alleles with distorted segregation can explain many curiosities. More recently, the selectionist-neutralist duopoly was broken by the realisation that biased gene conversion can explain phenomena such as mammalian isochore structures. An initial focus on unbiased transmission in 1919, has thus given way to an interest in biased transmission in 2019. A focus on very weak bias is now possible owing to technological advances, although technical biases may put a limit on resolving power. To understand the relevance of weak bias we could profit from having the concept of the effectively Mendelian allele, a companion to the effectively neutral allele. Understanding the implications of unbiased and biased transmission may, I suggest, be a good way to teach evolution so as to avoid psychological biases.
Gene-drive-mediated extinction is thwarted by population structure and evolution of sib mating
11202J. J. Bull, C. H. Remien and S. M. Krone, Evolution Medicine and Public Health, 2019:66-81. 2019-05-11 14:03:57.
Genetic engineering combined with CRISPR technology has developed to the point that gene drives can, in theory, be engineered to cause extinction in countless species. Success of extinction programs now rests on the possibility of resistance evolution, which is largely unknown. Depending on the gene-drive technology, resistance may take many forms, from mutations in the nuclease target sequence (e.g. for CRISPR) to specific types of non-random population structures that limit the drive (that may block potentially any gene-drive technology).
MGDrivE: A modular simulation framework for the spread of gene drives through spatially-explicit mosquito populations
3941Sánchez C, HMW, Sean L.; Bennett, Jared B.; Marshall, John M., Methods in Ecology and Evolution, 10:1-24. 2019-01-19 00:00:00.
Malaria, dengue, Zika, and other mosquito-borne diseases continue to pose a major global health burden through much of the world, despite the widespread distribution of insecticide-based tools and antimalarial drugs. The advent of CRISPR/Cas9-based gene editing and its demonstrated ability to streamline the development of gene drive systems has reignited interest in the application of this technology to the control of mosquitoes and the diseases they transmit. The versatility of this technology has enabled a wide range of gene drive architectures to be realized, creating a need for their population-level and spatial dynamics to be explored. 2.We present MGDrivE (Mosquito Gene Drive Explorer): a simulation framework designed to investigate the population dynamics of a variety of gene drive architectures and their spread through spatially-explicit mosquito populations. A key strength of the MGDrivE framework is its modularity: a) a genetic inheritance module accommodates the dynamics of gene drive systems displaying userdefined inheritance patterns, b) a population dynamic module accommodates the life history of a variety of mosquito disease vectors and insect agricultural pests, and c) a landscape module generates the metapopulation model by which insect populations are connected via migration over space. 3.Example MGDrivE simulations are presented to demonstrate the application of the framework to CRISPR/Cas9-based homing gene drive for: a) driving a disease-refractory gene into a population (i.e. population replacement), and b) disrupting a gene required for female fertility (i.e. population suppression), incorporating homing-resistant alleles in both cases. Further documentation and use examples are provided at the project's Github repository. 4.MGDrivE is an open-source R package freely available on CRAN. We intend the package to provide a flexible tool capable of modeling novel inheritance-modifying constructs as they are proposed and become available. The field of gene drive is moving very quickly, and we welcome suggestions for future development.
Modeling the mutation and reversal of engineered underdominance gene drives
3909Edgington, MPA, Luke S., Journal of Theoretical Biology, 479:14-21. 2019-01-07 00:00:00.
A range of gene drive systems have been proposed that are predicted to increase their frequency and that of associated desirable genetic material even if they confer a fitness cost on individuals carrying them. Engineered underdominance (UD) is such a system and, in one version, is based on the introduction of two independently segregating transgenic constructs each carrying a lethal gene, a suppressor for the lethal at the other locus and a desirable genetic “cargo”. Under this system individuals carrying at least one copy of each construct (or no copies of either) are viable whilst those that possess just one of the transgenic constructs are non-viable. Previous theoretical work has explored various properties of these systems, concluding that they should persist indefinitely in absence of resistance or mutation. Here we study a population genetics model of UD gene drive that relaxes past assumptions by allowing for loss-of-function mutations in each introduced gene. We demonstrate that mutations are likely to cause UD systems to break down, eventually resulting in the elimination of introduced transgenes. We then go on to investigate the potential of releasing “free suppressor” carrying individuals as a new method for reversing UD gene drives and compare this to the release of wild-types; the only previously proposed reversal strategy for UD. This reveals that while free suppressor carrying individuals may represent an inexpensive reversal strategy due to extremely small release requirements, they are not able to return a fully wild-type population as rapidly as the release of wild-types.
Controlling invasive rodents via synthetic gene drive and the role of polyandry
3927Manser, AC, S. J.; Sutter, A.; Blondel, D. V.; Serr, M.; Godwin, J.; Price, T. A. R., Proceedings of the Royal Society B-Biological Sciences, 286:9. 2019-01-05 00:00:00.
House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male's sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three-to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design.
Ecological effects on underdominance threshold drives for vector control
16267D. Khamis, C. El Mouden, K. Kura and M. B. Bonsall, Journal of Theoretical Biology, 456:1-15. 2018-11-07 16:39:27.
Here, ecological and epidemiological dynamics are coupled to a model of mosquito genetics to investigate theoretically the impact of different types of underdominance gene drive on disease prevalence. We model systems with two engineered alleles carried either on the same pair of chromosomes at the same locus or homozygously on different pairs at different loci, genetic lethality that affects both sexes or only females, and bi-sex or male-only releases.
Multiple loci of small effect confer wide variability in efficiency and resistance rate of CRISPR gene drive
11267J. Champer, Z. Wen, A. Luthra, R. Reeves, J. Chung, C. Liu, Y. L. Lee, J. Liu, E. Yang, P. W. Messer and A. G. Clark, bioRxiv, 447615. 2018-10-19 19:06:27.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. CRISPR homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles by homology-directed repair, increasing the frequency of the drive in a population. However, resistance alleles can form when end-joining repair takes place in lieu of homology-directed repair. Such alleles cannot be converted to drive alleles, which would halt the spread of a drive through a population. To investigate the effects of natural genetic variation on resistance formation, we developed a CRISPR homing gene drive in Drosophila melanogaster and crossed it into the genetically diverse Drosophila Genetic Reference Panel (DGRP) lines, measuring several performance parameters. Most strikingly, resistance allele formation post-fertilization in the early embryo ranged from 7% to 79% among lines and averaged 42±18%. We performed a Genome-Wide Association Study (GWAS) using our results in the DGRP lines and found that the resistance and conversion rates were polygenic, with several genetic polymorphisms showing relatively weak association. RNAi knockdown of several of these genes confirmed their effect, but their small effect sizes implies that their manipulation will yield only modest improvements to the efficacy of gene drives.
Invasion Success and Management Strategies for Social Vespula Wasps
13740P. J. Lester and J. R. Beggs, Annual Review of Entomology, 64:51-71. 2018-09-26 19:38:03.
Three species of Vespula have become invasive in Australia, Hawai'i, New Zealand, and North and South America and continue to spread. Economically, their main negative effect is associated with pollination and the apicultural industry. Climate change is likely to exacerbate their impacts in many regions. Although investigated extensively, no effective biological control agents have yet been found. Emerging technologies such as gene drives are under consideration.
A spatially discrete, integral projection model and its application to invasive carp
11503R. A. Erickson, E. A. Eager, P. M. Kocovsky, D. C. Glover, J. L. Kallis and K. R. Long, Ecological Modelling, 387:163-171. 2018-09-21 20:46:26.
Natural resource managers and ecologists often desire an understanding of spatial dynamics such as migration, dispersion, and meta-population dynamics. Network-node models can capture these salient features. Additionally, the state-variable used with many species may be appropriately modeled as a continuous variable (e.g., length) and management activities sometimes can only target individuals of certain sizes. Integral projection models (IPMs) can capture this life history characteristic and allow for the examination of size-specific management. We combined an IPM with a network-node model to capture both of these salient features. We then demonstrated how this model could be used to understand and manage populations of invasive species focusing on grass carp as an example. Grass carp disrupt ecosystems outside of their native range and have spread around much of the world, including North America. The impacts of grass carp include adversely changing aquatic plant communities, which in turn affect a wide range of endpoints ranging from water quality to waterfowl recruitment. We specifically examined two theoretical systems using parameters from the literature. First, we modeled a lake with two tributaries and examined how modified sterile males could be used as a control tool. We found that modified sterile males may be a feasible control tool to limit population growth. Second, we modeled a series of river pools and examined how harvest and deterrents could be used to decrease the risk of expanding grass carp's range within a river system. Within this system, we also compared the impacts of size specific harvest and uniform harvest across all sizes. We found that targeting the largest, spawning populations may be more important than targeting the populations close to the invasion front for reducing the risk of spreading grass carp. We also demonstrate that size of harvested fish was important for controlling populations.
Pest demography critically determines the viability of synthetic gene drives for population control
11505K. E. Wilkins, T. A. A. Prowse, P. Cassey, P. Q. Thomas and J. V. Ross, Mathematical Biosciences, 305:160-169. 2018-09-13 20:48:39.
Synthetic gene drives offer a novel solution for the control of invasive alien species. CRISPR-based gene drives can positively bias their own inheritance, and comprise a DNA sequence that is replicated by homologous recombination. Since gene drives can be positioned to silence fertility or developmental genes, they could be used for population suppression. However, the production of resistant alleles following self-replication errors threatens the technology's viability for pest eradication in real-world applications. Further, a robust assessment of how pest demography impacts the expected progression of gene drives through populations is currently lacking. We used a deterministic, two-sex, birth-death model to investigate how demographic assumptions affect the efficiency of suppression drives for controlling invasive rodents on islands, for two different gene-drive strategies. We show that mass-action reproduction results in overly optimistic eradication outcomes when compared to the more realistic assumption of polygynous breeding. When polygyny was assumed, both gene-strategies failed due to the evolution of resistance unless a reproductive Allee effect (reduced reproductive rates at low population density) was also included; although model outcomes were highly sensitive to the strength of this effect. Increasing the size of the initial gene-drive introduction (up to 10% of carrying capacity) had little impact on population outcomes. Understanding the demography of a population targeted for eradication is critical before the viability of gene-drive suppression can be adequately assessed.
Selfish genetic elements
3955Agren, JAC, A. G., PLOS Genetics, 14:20. 2018-01-13 00:00:00.
Selfish genetic elements (historically also referred to as selfish genes, ultra-selfish genes, selfish DNA, parasitic DNA, genomic outlaws) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, even if this has no or a negative effect on organismal fitness. [1-6] Genomes have traditionally been viewed as cohesive units, with genes acting together to improve the fitness of the organism. However, when genes have some control over their own transmission, the rules can change, and so just like all social groups, genomes are vulnerable to selfish behaviour by their parts. Early observations of selfish genetic elements were made almost a century ago, but the topic did not get widespread attention until several decades later. Inspired by the gene-centred views of evolution popularized by George Williams[7] and Richard Dawkins,[8] two papers were published back-to-back in Nature in 1980-by Leslie Orgel and Francis Crick[9] and Ford Doolittle and Carmen Sapienza[10] respectively-introducing the concept of selfish genetic elements (at the time called "selfish DNA") to the wider scientific community. Both papers emphasized that genes can spread in a population regardless of their effect on organismal fitness as long as they have a transmission advantage. Selfish genetic elements have now been described in most groups of organisms, and they demonstrate a remarkable diversity in the ways by which they promote their own transmission.[11] Though long dismissed as genetic curiosities, with little relevance for evolution, they are now recognized to affect a wide swath of biological processes, ranging from genome size and architecture to speciation.[12]
Sperm competition suppresses gene drive among experimentally evolving populations of house mice
4056Manser, AL, A. K.; Simmons, L. W.; Firman, R. C., Molecular Ecology, 26:5784-5792. 2017-01-14 00:00:00.
Drive genes are genetic elements that manipulate the 50% ratio of Mendelian inheritance in their own favour, allowing them to rapidly propagate through populations. The action of drive genes is often hidden, making detection and identification inherently difficult. Yet drive genes can have profound evolutionary consequences for the populations that harbour them: most known drivers are detrimental to organismal gamete development, reproduction and survival. In this study, we identified the presence of a well-known drive gene called t haplotype post hoc in eight replicate selection lines of house mice that had been evolving under enforced monandry or polyandry for 20 generations. Previous work on these selection lines reported an increase in sperm competitive ability in males evolving under polyandry. Here, we show that this evolutionary response can be partly attributed to gene drive. We demonstrate that drive-carrying males are substantially compromised in their sperm competitive ability. As a consequence, we found that t frequencies declined significantly in the polyandrous lines while remaining at stable, high levels in the monandrous lines. For the first time in a vertebrate, we thus provide direct experimental evidence that the mating system of a species can have important repercussions on the spread of drive genes over evolutionary relevant timescales. Moreover, our work highlights how the covert action of drive genes can have major, potentially unintended impact on our study systems.
Meiotic drive changes sperm precedence patterns in house mice: potential for male alternative mating tactics?
4104Sutter, AL, A. K., BMC Evolutionary Biology, 16:15. 2016-01-02 00:00:00.
Background: With female multiple mating (polyandry), male-male competition extends to after copulation (sperm competition). Males respond to this selective pressure through physiological, morphological and behavioural adaptations. Sperm competitiveness is commonly decreased in heterozygote carriers of male meiotic drivers, selfish genetic elements that manipulate the production of gametes in males. This might give carriers an evolutionary incentive to reduce the risk of sperm competition. Here, we explore this possibility in house mice. Natural populations frequently harbour a well-characterised male driver (t haplotype), which is transmitted to 90 % of heterozygous (+/t) males' offspring. Previous research demonstrated strong detrimental effects on sperm competitiveness, and suggested that +/t males are particularly disadvantaged against wild type males when first-to-mate. Low paternity success in the first-to-mate role is expected to favour male adaptations that decrease the risk of sperm competition by preventing female remating. Genotype-specific paternity patterns (sperm precedence) could lead to genetically determined alternative reproductive tactics that can spread through gene level selection. Here, we seek confirmation that +/t males are generally disadvantaged when first-to-mate and address whether males of different genotypes differ in reproductive tactics (copulatory and morphological) to maximise individual or driver fitness. Finally, we attempt to explain the mechanistic basis for alternative sperm precedence patterns in this species. Results: We confirmed that +/t males are weak sperm competitors when first to mate. When two +/t males competed, the second-to-mate was more successful, which contrasts with first male sperm precedence when wild type males competed. However, we found no differences between male genotypes in reproductive behaviour or morphology that were consistent with alternative reproductive tactics. Sperm of +/+ and +/t males differed with respect to in vitro sperm features. Premature hypermotility in +/t males' sperm can potentially explain why +/t males are very weak sperm competitors when first-to-mate. Conclusions: Our results demonstrate that meiotic drivers can have strong effects on sperm precedence patterns, and may provide a heritable basis for alternative reproductive tactics motivated by reduced sperm competitiveness. We discuss how experimental and evolutionary constraints may help explain why male genotypes did not show the predicted differences.
Sperm traits of masculinized fish relative to wild-type males: a systematic review and meta-analyses
11512A. M. Senior, S. L. Johnson and S. Nakagawa, Fish and Fisheries, 17:143-164. 2014-09-11 15:29:18.
Environmental sex reversal (ESR), whereby environmental effects (e.g. exogenous chemicals) override genetic sex determination, is a commonly used technique in aquaculture and physiology research. We performed a systematic review and meta-analyses of the literature that compares the sperm characteristics of masculinized genotypic females to wild-type males. We detected no mean differences between the ejaculate volume, sperm motility, duration or linearity of each type of male. We found some large mean differences in sperm concentration (d=2.541, CI=-0.004 to 5.086), reproductive success (d=-1.400, CI=-2.943 to 0.142), semen osmolality (d=1.850, CI=0.622 to 3.077) and sperm velocity (d=-0.933, CI=-1.426 to -0.441); in the case of the latter two traits, the mean effect was statistically significant. However, any significance did not stand up to a more conservative analysis. Additionally, heterogeneity was high and we found that where large differences between the sperm of sex-reversed and wild-type males are reported, these effects are attributable to sperm sampling methodology. Overall, we found little evidence for large systematic differences between the sperm produced by masculinized and wild-type male fish. Thus, masculinized genotypic females may enjoy reproductive success comparable to genotypic males. This conclusion leads to two potential implications: (i) sex-reversed fish may influence the dynamics of wild populations and (ii) aquaculture practices may use ESR to produce males with sperm quality similar to that of genotypic males. Most studies appear to have been performed in aquaculture species (i.e. Salmonidae); thus future experiments in non-model organisms may provide important insights in to the uniformity of the effects described.
Demographic effects on the use of genetic options for the control of mosquitofish, Gambusia holbrooki
11528R. E. Thresher, M. Canning and N. J. Bax, Ecological Applications, 23:801-814. 2013-06-01 15:57:26.
This study tests the sensitivity of genetically based pest control options based on sex ratio distortion to intra-and intersexual aggressive interactions that affect male and female survival and fitness. Data on these interactions and their impacts were gathered for the mosquitofish Gambusia holbrooki (Poeciliidae), a promiscuous species with a strongly male-biased operational sex ratio and well-documented male harassment of females. The experimental design consisted of an orthogonal combination of two population densities and three sex ratios, ranging from strongly male-biased to strongly female-biased, and long-term observations of laboratory populations. Contrary to expectations, the number of males in a population had little evident effect on population demographics. Rather, the density of adult females determined population fecundity (as a result of a stock-recruitment relationship involving females, but not males), constrained male densities (apparently as a result of cannibalism or intersexual aggression), and regulated itself (most likely through effects of intrasexual aggression on female recruitment). The principal effect of males was to constrain their own densities via effects of male-male aggression on adult male mortality rates. Through use of a realistically parameterized genetic/demographic model, we show that of three different genetic options applied to control G. holbrooki, one based on recombinant sex ratio distortion (release of Female Lethal carriers) is marginally more efficient than a sterile male release program, and both outperform an option based on chromosomal sex ratio distortion (Trojan W). Nonlinear dependence of reproductive rate on female density reduces the efficacy of all three approaches. The major effect of intra-and intersexual aggression is mediated through females, whose interactions reduce female numbers and increase the efficacy of a control program based on sex ratio. Socially mediated male mortality has a small impact on control programs due to operational sex ratios that are heavily male-biased. The sensitivity of sex ratio-based control options to social factors will depend on the mating system of the targeted pest, but evidence of widespread density-dependent population regulation suggests that, for most species, the effects of elevated adult mortality (due to intra-and intersexual aggression) on control programs are likely to be slight.
Analysis of the Trojan Y chromosome model for eradication of invasive species in a dendritic riverine system
11532J. B. Gutierrez, M. K. Hurdal, R. D. Parshad and J. L. Teem, Journal of Mathematical Biology, 64:319-340. 2011-03-04 17:07:15.
The use of Trojan Y chromosomes has been proposed as a genetic strategy for the eradication of invasive species. The strategy is particularly relevant to invasive fish species that have XY sex determination system and are amenable to sex-reversal. In this paper we study the dynamics of an invasive fish population occupying a dendritic domain in which Trojan individuals bearing multiple Y chromosomes have been released as a means of eradication. We demonstrate the existence of a bounded absorbing set that represents extinction of the invasive species irrespective of the dendritic configuration. The method of analysis used to obtain global estimates could be applied to other population problems and other geometries.
On the global attractor of the Trojan Y chromosome model.
11536R. D. Parshad and J. B. Gutierrez, Communications on Pure and Applied Analysis, 10:339-359. 2010-01-01 17:11:02.
We consider the Trojan Y Chromosome (TYC) model for eradication of invasive species in population dynamics. We present global estimates for the TYC system in a spatial domain. In this work we prove the existence of a global attractor for the system. We derive uniform estimates to tackle the question of asymptotic compactness of the semi-group for the TYC model in H(2)(Omega). This along with the existence of a bounded absorbing set, which we also derive, demonstrates the existence of a global attractor for the TYC model. The present analysis reveals that extinction of an invasive species is always possible to achieve irrespective of geometric considerations of the domain. This result is valid for TYC systems in which advection is negligible. This theoretical work lays the foundation for experimental studies of the application of the TYC eradication strategy in spatial ecology, since the outcome is in principle guaranteed.
Selfish DNA and breeding system in flowering plants
4366Burt, AT, R., Proceedings of the Royal Society B-Biological Sciences, 265:141-146. 1998-01-04 00:00:00.
In many species, some individuals carry one or more B chromosomes: extra, or supernumerary chromosomes not part of the normal complement. In most well-studied cases, B's lower the fitness of their carrier and persist in populations only because of accumulation mechanisms analogous to meiotic drive. It has been suggested that such genomic parasites are expected to persist only in outcrossed sexual species, in which uninfected lines of descent can be continuously reinfected; in inbred or asexual species, all selection is between lines of descent, and the genomic parasites are either lost or must evolve into commensals or mutualists. Here we present a simple population genetic model of the effect of outcrossing rate on the frequency of B chromosomes, and find that outcrossing facilitates the spread of parasitic B's, but inhibits the spread of mutualists. Data compiled from the literature on breeding system and B chromosomes of British plants indicate that B's are much more likely to be reported from obligately outcrossed species than inbred species. These results support the ideas that most B chromosomes are parasitic, and that breeding systems play a central role in the biology of selfish genes.
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