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The use of genomic and phenotypic data to scan for outliers is a mainstay for studies of hybridization and speciation. Geographic cline analysis of natural hybrid zones is widely used to identify putative signatures of selection by detecting deviations from baseline patterns of introgression. As with other outlier-based approaches, demographic histories can make neutral regions appear to be under selection and vice versa. In this study, we use a forward-time individual-based simulation approach to evaluate the robustness of geographic cline analysis under different evolutionary scenarios. We modelled multiple stepping-stone hybrid zones with distinct age, deme sizes, and migration rates, and evolving under different types of selection. We found that drift distorts cline shapes and increases false positive rates for signatures of selection. This effect increases with hybrid zone age, particularly if migration between demes is low. Drift can also distort the signature of deleterious effects of hybridization, with genetic incompatibilities and particularly underdominance prone to spurious typing as adaptive introgression. Our results suggest that geographic clines are most useful for outlier analysis in young hybrid zones with large populations of hybrid individuals. Current approaches may overestimate adaptive introgression and underestimate selection against maladaptive genotypes.

There is a critical need for further research into methods to control biological populations. Numerous challenges to agriculture, ecological systems, and human health could be mitigated by the targeted reduction and management of key species (e.g. pests, parasites, and vectors for pathogens). The discovery and adaptation of the CRISPR/Cas editing platform co-opted from bacteria has provided a mechanism for a means to alter an entire population. A CRISPR-based gene drive system can allow for the forced propagation of a genetic element that bypasses Mendelian inheritance which can be used to bias sex determination, install exogenous information, or remove endogenous DNA within an entire species. Laboratory studies have demonstrated the potency by which gene drives can operate within insects and other organisms. However, continued research and eventual application face serious opposition regarding issues of policy, biosafety, effectiveness, and reversal. Previous mathematical work has suggested the use of modified gene drive designs that are limited in spread such as daisy chain or underdominance drives. However, no system has yet been proposed that allows for an inducible reversal mechanism without requiring the introduction of additional individuals. Here, we study gene drive effectiveness, fitness, and inducible drive systems that could respond to external stimuli expanding from a previous frequency-based population model. We find that programmed modification during gene drive propagation could serve as a potent safeguard to either slow or completely reverse drive systems and allow for a return to the original wild-type population.

Recent advances in gene‐editing technologies have opened new avenues for genetic pest control strategies, in particular around the use of gene drives to suppress or modify pest populations. Significant uncertainty, however, surrounds the applicability of these strategies to novel target species, their efficacy in natural populations and their eventual safety and acceptability as control methods. In this article, we identify issues associated with the potential use of gene drives in agricultural systems, to control pests and diseases that impose a significant cost to agriculture around the world. We first review the need for innovative approaches and provide an overview of the most relevant biological and ecological traits of agricultural pests that could impact the outcome of gene drive approaches. We then describe the specific challenges associated with using gene drives in agricultural systems, as well as the opportunities that these environments may offer, focusing in particular on the advantages of high‐threshold gene drives. Overall, we aim to provide a comprehensive view of the potential opportunities and the remaining uncertainties around the use of gene drives in agricultural systems.

Investigating the origin of parthenogenesis through interspecific hybridization can provide insight into how meiosis may be altered by genetic incompatibilities, which is fundamental for our understanding of the formation of reproductive barriers. Yet the genetic mechanisms giving rise to obligate parthenogenesis in eukaryotes remain understudied. In the microcrustacean Daphnia pulex species complex, obligately parthenogenetic (OP) isolates emerged as backcrosses of two cyclically parthenogenetic (CP) parental species, D. pulex and D. pulicaria, two closely related but ecologically distinct species. We examine the genome-wide expression in OP females at the early resting egg production stage, a life-history stage distinguishing OP and CP reproductive strategies, in comparison to CP females of the same stage from the two parental species. Our analyses of the expression data reveal that misregulated genes (underdominant and overdominant genes) are abundant in OP isolates, suggesting widespread regulatory incompatibilities between the parental species. More importantly, underdominant genes (i.e., genes with expression lower than both parentals) in the OP isolates are enriched in meiosis and cell-cycle pathways, indicating an important role of underdominance in the origin of obligate parthenogenesis. Furthermore, metabolic and biosynthesis pathways enriched with overdominant genes (i.e., expression higher than both parentals) are another genomic signature of OP isolates.

The spread of synthetic gene drives is often discussed in the context of panmictic populations connected by gene flow and described with simple deterministic models. Under such assumptions, an entire species could be altered by releasing a single individual carrying an invasive gene drive, such as a standard homing drive. While this remains a theoretical possibility, gene drive spread in natural populations is more complex and merits a more realistic assessment. The fate of any gene drive released in a population would be inextricably linked to the population's ecology. Given the uncertainty often involved in ecological assessment of natural populations, understanding the sensitivity of gene drive spread to important ecological factors is critical. Here we review how different forms of density dependence, spatial heterogeneity, and mating behaviors can impact the spread of self-sustaining gene drives. We highlight specific aspects of gene drive dynamics and the target populations that need further research.

The successful implementation of heterosis in rice has significantly enhanced rice productivity, but the genetic basis of heterosis in rice remains unclear. To understand the genetic basis of heterosis in rice, main-effect and epistatic quantitative trait loci (QTLs) associated with heterosis for grain yield-related traits in the four related rice mapping populations derived from Xiushui09 (XS09) (japonica) and IR2061 (indica), were dissected using single nucleotide polymorphism bin maps and replicated phenotyping experiments under two locations. Most mid-parent heterosis of testcross F1s (TCF1s) of XS09 background introgression lines (XSILs) with Peiai64S were significantly higher than those of TCF1s of recombinant inbred lines (RILs) with PA64S at two locations, suggesting that the effects of heterosis was influenced by the proportion of introgression of IR2061’s genome into XS09 background. A total of 81 main-effect QTLs (M-QTLs) and 41 epistatic QTLs were identified for the phenotypic variations of four traits of RILs and XSILs, TCF1s and absolute mid-parent heterosis in two locations. Furthermore, overdominance and underdominance were detected to play predominant effects on most traits in this study, suggesting overdominance and underdominance as well as epistasis are the main genetic bases of heterosis in rice. Some M-QTLs exhibiting positive overdominance effects such as qPN1.2, qPN1.5 and qPN4.3 for increased panicle number per plant, qGYP9 and qGYP12.1 for increased grain yield per plant, and qTGW3.4 and qTGW8.2 for enhanced 1000-grain weight would be highly valuable for breeding to enhance grain yield of hybrid rice by marker-assisted selection.

We explore the interaction between two genetic incompatibilities (underdominant loci in diploid organisms) in a population occupying a one-dimensional space. We derive a system of partial differential equations describing the dynamics of allele frequencies and linkage disequilibrium between the two loci, and use a quasi-linkage equilibrium approximation in order to reduce the number of variables. We investigate the solutions of this system and demonstrate the existence of a solution in which the two clines in allele frequency remain stacked together. In the case of asymmetric incompatibilities (i.e. when one homozygote is favored over the other at each locus), these stacked clines propagate in the form of a traveling wave. We obtain an approximation for the speed of this wave which, in particular, is decreased by recombination between the two loci but is always larger than the speed of "one cline alone".

1AbstractEngineered gene drive techniques for population replacement and/or suppression have potential for tackling complex challenges, including reducing the spread of diseases and invasive species. Unfortunately, the self-propelled behavior of drives can lead to the spread of transgenic elements beyond the target population, which is concerning. Gene drive systems with a low threshold frequency for invasion, such as homing-based gene drive systems, require initially few transgenic individuals to spread and are therefore easy to implement. However their ease of spread presents a double-edged sword; their low threshold makes these drives much more susceptible to spread outside of the target population (spillover). We model a proposed drive system that transitions in time from a low threshold drive system (homing-based gene drive) to a high threshold drive system (underdominance) using daisy chain technology. This combination leads to a spatially restricted drive strategy, while maintaining an attainable release threshold. We develop and analyze a discrete-time model as proof of concept and find that this technique effectively generates stable local population suppression, while preventing the spread of transgenic elements beyond the target population under biologically realistic parameters.

Mosquito-borne diseases cause significant social and economic damage across much of the globe. New biotechnologies that utilise manipulations of the mosquito genome have been developed to combat disease. The successful implementation of genetic mosquito control technologies may depend upon ecological, evolutionary and environmental factors, as well as the specifications of the chosen technology. Understanding the influence of these external factors will help inform how best to deploy a chosen technology to control vectors of infectious diseases. We use a continuous-time stochastic spatial network model of a mosquito life-cycle coupled to population genetics models to investigate the impact of releasing seven types of genetic control technology: a self-limiting lethal gene, two underdominance threshold gene drives, two homing gene drives and twoWolbachiasystems. We apply the mathematical framework to understand control interventions of two archetypes of mosquito species: a short-range dispersingAedes aegyptiand comparatively longer-range dispersingAnopheles gambiae. We show that mosquito dispersal behaviour is an extremely important factor in determining the outcome of a release programme. Assortative mating – where the mating success of genetically modified males is lower than their wild counterparts – can facilitate the spatial containment of gene drives. The rapid evolution of strong mating preference can damage the efficacy of control efforts for all control technologies. We suggest that there cannot be a one-size-fits-all approach to regulation and implementation of vector control; there must be application-specific control plans that take account of understudied ecological, evolutionary and environmental factors.

Heterosis improves growth and survival of shellfish species. Although breeders have widely exploited heterosis, its underlying molecular mechanisms remain unclear. In this study, a 2 × 2 complete diallel cross was facilitated between two full‐sib families to produce two inbred families (A and D) and their reciprocal hybrid families (B and C) of pearl oyster Pinctada fucata martensii. Growth traits of the four families were compared at the adult stages. Transcriptome analysis was conducted on the four families using an Illumina sequencing platform. The results revealed that the growth traits of the four families significantly varied (P

Mosquito-borne diseases, such as malaria, dengue and chikungunya, cause morbidity and mortality around the world. Recent advances in gene drives have produced control methods that could theoretically modify all populations of a disease vector, from a single release, making whole species less able to transmit pathogens. This ability has caused both excitement, at the prospect of global eradication of mosquito-borne diseases, and concern around safeguards. Drive mechanisms that require individuals to be released at high frequency before genes will spread can therefore be desirable as they are potentially localised and reversible. These include underdominance-based strategies and use of the reproductive parasite Wolbachia. Here, we review recent advances in practical applications and mathematical analyses of these threshold-dependent gene drives with a focus on implementation in Aedes aegypti, highlighting their mechanisms and the role of fitness costs on introduction frequencies. Drawing on the parallels between these systems offers useful insights into practical, controlled application of localised drives, and allows us to assess the requirements needed for gene drive reversal.

Highlights • A model of engineered underdominance (UD) gene drive is proposed. • Numerical results suggest that UD could be an effective tool for disease control. • Success/failure of UD is affected by release strategy and fitness of mosquitoes. • A single release of only males with weakly suppressed lethals cannot succeed., Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually suppressing lethals. In such a system two genetic constructs are introduced, each possessing a lethal element and a suppressor of the lethal at the other locus. Specifically, we formulate and analyse a population genetics model of this system to assess when different combinations of release strategies (i.e. single or multiple releases of both sexes or males only) and genetic systems (i.e. bisex lethal or female-specific lethal elements and different strengths of suppressors) will give population replacement or fail to do so. We anticipate that results presented here will inform the future design of engineered underdominance gene drive systems as well as providing a point of reference regarding release strategies for those looking to test such a system. Our discussion is framed in the context of genetic control of insect vectors of disease. One of several serious threats in this context are Aedes aegypti mosquitoes as they are the primary vectors of dengue viruses. However, results are also applicable to Ae. aegypti as vectors of Zika, yellow fever and chikungunya viruses and also to the control of a number of other insect species and thereby of insect-vectored pathogens.

Underdominance systems can quickly spread through a population, but only when introduced in considerable numbers. This promises a gene drive mechanism that is less invasive than homing drives, potentially enabling new approaches in the fight against vector-borne diseases. If regional confinement can indeed be achieved, the decision-making process for a release would likely be much simpler compared to other, more invasive types of drives. The capacity of underdominance gene drive systems to spread in a target population without invading other populations is typically assessed via network models of panmictic demes linked by migration. However, it remains less clear how such systems would behave in more realistic population models where organisms move over a continuous landscape. Here, we use individual-based simulations to study the dynamics of several proposed underdominance systems in continuous-space. We find that all these systems can fail to persist in such environments, even after an initially successful establishment in the release area, confirming previous theoretical results from diffusion theory. At the same time, we find that a two-locus two-toxin-antidote system can invade connected demes through a narrow migration corridor. This suggests that the parameter space where underdominance systems can establish and persist in a release area while at the same time remaining confined to that area could be quite limited, depending on how a population is spatially structured. Overall, these results indicate that realistic spatial context must be considered when assessing strategies for the deployment of underdominance drives.

Background The discovery of CRISPR-based gene editing and its application to homing-based gene drive systems has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. Gene drive systems that display threshold-dependent behavior could potentially be used during the trial phase of this technology, or when localized control is otherwise desired, as simple models predict them to spread into partially isolated populations in a confineable manner, and to be reversible through releases of wild-type organisms. Here, we model hypothetical releases of two recently engineered threshold-dependent gene drive systems—reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL—to explore their ability to be confined and remediated. Results We simulate releases of Aedes aegypti, the mosquito vector of dengue, Zika, and other arboviruses, in Yorkeys Knob, a suburb of Cairns, Australia, where previous biological control interventions have been undertaken on this species. We monitor spread to the neighboring suburb of Trinity Park to assess confinement. Results suggest that translocations could be introduced on a suburban scale, and remediated through releases of non-disease-transmitting male mosquitoes with release sizes on the scale of what has been previously implemented. UDMEL requires fewer releases to introduce, but more releases to remediate, including of females capable of disease transmission. Both systems are expected to be confineable to the release site; however, spillover of translocations into neighboring populations is less likely. Conclusions Our analysis supports the use of translocations as a threshold-dependent drive system capable of spreading disease-refractory genes into Ae. aegypti populations in a confineable and reversible manner. It also highlights increased release requirements when incorporating life history and population structure into models. As the technology nears implementation, further ecological work will be essential to enhance model predictions in preparation for field trials.

This study aimed to test mate choice and selection during early life stages on major histocompatibility (MH) genotype in natural families of Atlantic salmon Salmo salar spawners and juveniles, using nine microsatellites to reconstruct families, one microsatellite linked to an MH class I gene and one minisatellite linked to an MH class II gene. MH-based mate choice was only detected for the class I locus on the first year, with lower expected heterozygosity in the offspring of actually mated pairs than predicted under random mating. The genotype frequencies of MH-linked loci observed in the juveniles were compared with frequencies expected from Mendelian inheritance of parental alleles to detect selection during early life stages. No selection was detected on the locus linked to class I gene. For the locus linked to class II gene, observed heterozygosity was higher than expected in the first year and lower in the second year, suggesting overdominance and underdominance, respectively. Within family, juveniles' body size was linked to heterozygosity at the same locus, with longer heterozygotes in the first year and longer homozygotes in the second year. Selection therefore seems to differ from one locus to the other and from year to year.

When a new gene arrangement is generated by spontaneous mutation its survival is uncertain and largely unaffected by associated fitness effects. However, if a new chromosomal inversion is introduced into a population already polymorphic for inversions, then its survival probability will be a function of the relative size, position, and linkage phase of the gene rearrangements. This dependence on structural features is due to the complex meiotic behavior of overlapping inversions generating asymmetric dyads, which in turn cause both underdominance and meiotic drive/drag. Therefore, survival probabilities of new inversions can be expressed in terms of the probability of forming an asymmetric dyad via crossing over in meiosis I and the probability of recovery from that asymmetric dyad during disjunction in meiosis II. This model of female meiotic drive was parameterized with data from published experiments on laboratory constructs inDrosophila melanogaster. Generalizing this analysis to all possible inversions predicts a bias towards larger, proximally located inversions having a shorter persistence time in populations. These population genetic predictions are consistent with cytological evidence from natural populations ofD. melanogaster. This research mathematically formalizes a cytogenetic mechanism for female meiotic drive/drag as the major force governing behavior of new gene arrangements entering populations, and therefore determining the genomic distribution of segregating inversion polymorphism.

Underdominance gene drive systems promise a mechanism for rapidly spreading payload alleles through a local population while otherwise remaining confined, unable to spread into neighboring populations due to their frequency-dependent dynamics. Such systems could provide a new tool in the fight against vector-borne diseases by disseminating transgenic payloads through vector populations. If local confinement can indeed be achieved, the decision-making process for the release of such constructs would likely be considerably simpler compared to other gene drive mechanisms such as CRISPR homing drives. So far, the confinement ability of underdominance systems has only been demonstrated in models of panmictic populations linked by migration. How such systems would behave in realistic populations where individuals move over continuous space remains largely unknown. Here, we study several underdominance systems in continuous-space population models and show that their dynamics are drastically altered from those in panmictic populations. Specifically, we find that all underdominance systems we studied can fail to persist in such environments, even after successful local establishment. At the same time, we find that a two-locus two-toxin-antitoxin system can still successfully invade neighboring populations in many scenarios even under weak migration. This suggests that the parameter space for underdominance systems to both establish in a given region and remain confined to that region would likely be highly limited. Overall, these results indicate that spatial context must be considered when assessing strategies for the deployment of underdominance systems.

Underdominance gene drives are frequency-dependent drives that aim to spread a desired homozygote genotype within a population. When the desired homozygote is released above a threshold frequency, heterozygote fitness disadvantage acts to drive the desired trait to fixation. Underdominance drives have been proposed as a way to control vector-borne disease through population suppression and replacement in a spatially contained and reversible way—benefits that directly address potential safety concerns with gene drives. 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. Further, the different genetic and ecological fitness costs that can arise from genetic modification and artificial rearing are investigated through their effect on the population threshold frequency that is required to trigger the drive mechanism. We show that male-only releases must be significantly larger than bi-sex releases to trigger the underdominance drive. In addition, we find that female-specific lethality averts a higher percentage of disease cases over a control period than does bi-sex lethality. Decreases in the genetic fitness of the engineered homozygotes can increase the underdominance threshold substantially, but we find that the mating success of transgenic mosquitoes with wild-type females (influenced by a lack of competitiveness or the evolution of behavioural resistance in the form of active female mate preference) and the longevity of artificially-reared mosquitoes are vitally important to the success chances of underdominance based gene drive control efforts.

Background and aims Arbuscular mycorrhizal fungi (AMF) play an important role in plant nutrition and protection against pests and diseases, as well as in soil structuration, nutrient cycling and, generally speaking, in sustainable agriculture, particularly under drought, salinity and low input or organic agriculture. However, little is known about the genetics of the AMF-plant association in tomato. The aim of this study was the genetic analysis of root AMF colonization in tomato via the detection of the quantitative trait loci (QTLs) involved. Methods A population of 130 recombinant inbred lines derived from the wild species Solanum pimpinellifolium, genotyped for 1899 segregating, non-redundant single nucleotide polymorphisms (SNPs) from the SolCAP tomato panel, was characterized for intensity, frequency and arbuscular abundance of AMF colonization to detect the QTLs involved and to analyse the genes within their peaks (2-2.6 Mbp). Key results The three AMF colonization parameters were highly correlated (0.78-0.97) and the best one, with the highest heritability (0.23), corresponded to colonization intensity. A total of eight QTLs in chromosomes 1, 3, 4, 5, 6, 8, 9 and 10 were detected. Seven of them simultaneously affected intensity and arbuscule abundance. The allele increasing the expression of the trait usually came from the wild parent in accordance with the parental means, and several epistatic interactions were found relevant for breeding purposes. SlCCaMK and SlLYK13 were found among the candidate genes. Carbohydrate transmembrane transporter activity, lipid metabolism and transport, metabolic processes related to nitrogen and phosphate-containing compounds, regulation of carbohydrates, and other biological processes involved in the plant defence were found to be over-represented within the QTL peaks. Conclusions Intensity is genetically the best morphological measure of tomato root AMF colonization. Wild alleles can improve AMF colonization, and the gene contents of AMF colonization QTLs might be important for explaining the establishment and functioning of the AMF-plant symbiosis.

Replacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions provides self-perpetuating methods of disease prevention and population suppression, respectively. Gene drive mechanisms that require the gene drive element and linked cargo exceed a high threshold frequency to spread are attractive because they offer several points of control: they bring about local, but not global population replacement; and transgenes can be eliminated by reintroducing wildtypes into the population so as to drive the frequency of transgenes below the threshold required for drive. It has long been recognized that reciprocal chromosome translocations could, in principal, be used to bring about high threshold gene drive through a form of underdominance. However, translocations able to drive population replacement have not been reported, leaving it unclear if translocation-bearing strains fit enough to mediate gene drive can easily be generated. Here we use modeling to identify a range of conditions under which translocations should spread, and the equilibrium frequencies achieved, given specific introduction frequencies, fitness costs and migration rates. We also report the creation of engineered translocation-bearing strains ofDrosophila melanogaster, generated through targeted chromosomal breakage and homologous recombination. By several measures translocation-bearing strains are fit, and drive high threshold, reversible population replacement in laboratory populations. These observations, together with the generality of the tools used to generate translocations, suggest that engineered translocations may be useful for controlled population replacement in many species.

The requirement to develop new techniques for insect control that minimize negative environmental impacts has never been more pressing. Here we discuss population suppression and population replacement technologies. These include sterile insect technique, genetic elimination methods such as the release of insects carrying a dominant lethal (RIDL), and gene driving mechanisms offered by intracellular bacteria and homing endonucleases. We also review the potential of newer or underutilized methods such as reproductive interference, CRISPR technology, RNA interference (RNAi), and genetic underdominance. We focus on understanding principles and potential effectiveness from the perspective of evolutionary biology. This offers useful insights into mechanisms through which potential problems may be minimized, in much the same way that an understanding of how resistance evolves is key to slowing the spread of antibiotic and insecticide resistance. We conclude that there is much to gain from applying principles from the study of resistance in these other scenarios – specifically, the adoption of combinatorial approaches to minimize the spread of resistance evolution. We conclude by discussing the focused use of GM for insect pest control in the context of modern conservation planning under land‐sparing scenarios.

A number of different genetics-based vector control methods have been proposed. Two approaches currently under development in Aedes aegypti mosquitoes are the two-locus engineered underdominance and killer-rescue gene drive systems. Each of these is theoretically capable of increasing in frequency within a population, thus spreading associated desirable genetic traits. Thus they have gained attention for their potential to aid in the fight against various mosquito-vectored diseases. In the case of engineered underdominance, introduced transgenes are theoretically capable of persisting indefinitely (i.e. it is self-sustaining) whilst in the killer-rescue system the rescue component should initially increase in frequency (while the lethal component (killer) is common) before eventually declining (when the killer is rare) and being eliminated (i.e. it is temporally self-limiting). The population genetics of both systems have been explored using discrete generation mathematical models. The effects of various ecological factors on these two systems have also been considered using alternative modelling methodologies. Here we formulate and analyse new mathematical models combining the population dynamics and population genetics of these two classes of gene drive that incorporate ecological factors not previously studied and are simple enough to allow the effects of each to be disentangled. In particular, we focus on the potential effects that may be obtained as a result of differing ecological factors such as strengths of larval competition; numbers of breeding sites; and the relative fitness of transgenic mosquitoes compared with their wild-type counterparts. We also extend our models to consider population dynamics in two demes in order to explore the effects of dispersal between neighbouring populations on the outcome of UD and KR gene drive systems., Author summary Vector-borne diseases represent a severe burden to both human and animal health worldwide. The methods currently being used to control a range of these diseases do not appear sufficient to address the issues at hand. As such, alternate methods for the control of vector-borne diseases are currently being investigated. Among the promising techniques currently being considered are a range of genetic control methods known as gene drive systems. These allow desirable genetic traits (such as a much reduced capacity for vectors to transmit viruses) to be spread through a target population; taking advantage of natural mate seeking behaviour to locate vector sub-populations that can be extremely difficult for humans to locate and reach. Here we use mathematical models (parameterised to consider mosquito populations) to demonstrate the robustness of the engineered underdominance and killer-rescue classes of gene drive to different ecological factors including birth and death rates; the number and quality of breeding sites (i.e. carrying capacity); and the strength of density-dependent competition during the larval development phase. We then go on to explore the range of potential outcomes that may result from the migration of individuals between two neighbouring populations.

Highlights • A model with mutation in engineered underdominance gene drive components is proposed. • Loss-of-function mutations are likely to cause elimination of the gene drive. • The gene drive is likely to persist at high frequency for hundreds of generations. • Engineered underdominance can be reversed by release of free-suppressor constructs. • Free-suppressors can reverse engineered underdominance with extremely small releases., 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.

International audience; Chromosomal change is recognized as an important force in speciation-with-gene-flow models. Although Robertsonian (Rb) translocations contribute to hybrid unfitness and modify recombination patterns, they are generally not considered as efficient as inversions in reducing gene flow. The present study analyses two hybridizing chromosomal races of the house mouse (Mus musculus domesticus), one carrying nine Rb fusions (2n = 22) and the other carrying the ancestral karyotype (2n = 40). Chromosomal heterozygosity involves simple meiotic configurations, the underdominance of which is not as efficient in promoting speciation as more complex chromosomal differences. The pattern of divergence between these races was investigated using 32 microsatellite loci distributed over all autosomes. The results highlighted a relatively large differentiation between the two chromosomal races. The contribution of variation in recombination patterns to this differentiation was supported by the contrasting levels of divergence between proximal vs. non-proximal microsatellite loci. Clinal analyses of the Rb fusions through the hybrid zone uncovered differences in steepness between metacentrics, suggesting associated differences in selection which did not involve linked genic incompatibilities. This study illustrates the significant role of Rb-associated changes in recombination in promoting or maintaining divergence between chromosomal races of the house mouse.