Evolutionary Applications

The European flat oyster (Ostrea edulis), like numerous other oyster species, has been exploited for millennia and cultivated and translocated for centuries. Following a severe population decline, and in the context of ongoing conservation and restoration programs, genetic considerations must now be addressed to avoid mistakes. The objective of our study was to complement population genetic studies conducted at various scales along European coasts. Our sampling primarily targeted the French Atlantic, English Channel, and Mediterranean coasts, aiming to provide a fine-scale genetic characterization of populations in these regions. By integrating SNP array and low-coverage sequencing datasets, we obtained a comprehensive overview of the population genetic structure of Ostrea edulis across western Europe. Most previously identified clusters in Western Europe were confirmed. In France, populations assigned to these clusters exhibited notable within-patch homogeneity. However, two key findings emerged: (1) an extensive overlap zone between the Atlantic and western Mediterranean clusters, spanning at least from southern Portugal to southern France, and (2) the detection of a novel, clearly distinct cryptic cluster east of the English Channel, whose geographic range remains to be better delineated. These insights are critical for informing management decisions, particularly as restoration and conservation plans are currently being implemented across the species range.

Genetic interventions to modify wild population densities are typically framed around pest suppression, with parallel approaches for boosting beneficial or endangered populations remaining largely undeveloped. Imposing a sustained but non-eliminative genetic load could in principle address both objectives, but existing designs rely on genes with intermediate fitness effects whose loads are difficult to predict under field conditions. Here we describe engineered balanced lethal systems, in which CRISPR-based gene drive establishes two complementing recessive-lethal alleles at a single locus, producing a sustained 50% load through Mendelian segregation. Modelling shows these systems spread from small releases, and that the resulting population-level consequences depend on density regulation and on the timing of lethality: the same 50% load can suppress pests, boost populations of beneficial or endangered species, dampen boom-bust cycles, or raise effective population size. Additional systems at independent loci scale the effect in stepwise increments, and a split-drive variant localises it geographically. These results demonstrate that gene drives imposing genetic load can be expanded beyond elimination, to support and preserve beneficial and endangered populations.

Genomic offset (GO) is increasingly used to predict population maladaptation risk under climate change, with larger offsets assumed to indicate greater vulnerability. Despite rapid adoption in conservation planning, it remains unclear how sensitive GO estimates are to key methodological choices, including SNP set composition, genotype-environment association (GEA) methods, and the specific GO metric used. Empirical validation against observed population dynamics also remains limited. Here, we evaluate the methodological robustness and predictive performance of GO using multidecadal demographic monitoring data from Lycaeides butterflies, a system with short generation times and high fecundity that may facilitate rapid adaptive responses. GO estimates were broadly consistent across SNP sets, regardless of composition or size, with climate-associated and randomly selected SNPs yielding largely concordant values. Consistency across GEA methods was moderate and depended on the SNP set used. In contrast, GO metrics differed substantially in the magnitude of maladaptation estimated, suggesting they capture distinct biological signals and should not be treated as interchangeable. Crucially, GO was a poor predictor of observed population trends, regardless of SNP set composition, GO metric, or GEA method, both at sites used to fit GEA models and when extrapolated to independent demographic sites. These findings suggest that, while GO provides a valuable conceptual framework for assessing potential maladaptation, its quantitative estimates and predictive power are sensitive to methodological choices and species-specific biological context. We therefore urge careful alignment of GO metric assumptions with conservation objectives, along with rigorous empirical validation, before GO estimates are used to inform management decisions.

Thermal history provenancing can guide the choice of parental broodstock for selective breeding of corals from distinct reefs and has been proposed as an intervention for enhancing climate resilience. However, the genetic and molecular mechanisms underlying resultant offspring responses to heat stress, particularly during early life stages, remain poorly understood. Here, we generated Acropora tersa larvae and recruits by crossing parental colonies from the historically warmer Martin Reef and cooler Davies Reef and assessed the effects of within- and between-reef crosses on genetic diversity and transcriptional responses to heat stress. Genome-wide single nucleotide polymorphism analyses showed that broodstock from Martin and Davies Reefs were weakly differentiated (FST = 0.008) and exhibited comparable heterozygosity, as did all larval offspring groups. Transcriptomic analyses of recruits exposed to heat stress (32 {degrees}C for 36 days) revealed that both within- and between-reef offspring groups activated conserved stress-response pathways, with seven genotype-independent heat-responsive genes detected across all offspring groups. Differential expression and enrichment analyses showed induction of defence, protein homeostasis, intracellular transport, and metabolic processes alongside repression of growth- and signalling-related functions, consistent with the Type A General Coral Stress Response. Taken together, these findings suggest that the benefits of thermal history provenancing-informed selective breeding may be limited in low-differentiation systems and that targeted pre-screening of broodstock may help capture functional genetic variation relevant to restoration applications.

Morus rubra is native to the eastern United States, with its range extending into the Upper Midwest and southern Ontario, Canada. Its present distribution suggests that past glacial events in North America may have influenced the genetic structure of populations at the species northwestern range boundary. This study assessed genetic variation among six M. rubra populations believed to have experienced postglacial colonization using published nuclear microsatellite markers and sequences from the chloroplast trnL-trnF region. Five nuclear microsatellite markers previously developed for M. alba were successfully transferred to M. rubra, while the chloroplast trnL-trnF region provided an additional marker for evaluating chlorotype diversity. Nuclear microsatellite diversity was higher in southern unglaciated populations than in northern glaciated populations, a pattern consistent with the observed distribution of chlorotype diversity. Together, these results support ancient founder effects associated with leading-edge expansion following glacial recession and suggest that postglacial colonization contributed to the present-day genetic structure of M. rubra at its northwestern range boundary. Because M. rubra hybridizes with the naturalized invasive M. alba, reduced genetic diversity in marginal populations may increase their vulnerability to genetic swamping. The markers characterized in this study provide useful tools for population genetic research in Morus, and the findings have important implications for the conservation and management of marginal and threatened M. rubra populations in the Upper Midwest.

BackgroundLyme borreliosis is a common tick-borne disease in Europe caused by spirochetes of the Borrelia burgdorferi sensu lato complex, including Borrelia afzelii, which is maintained in nature through interactions with rodent reservoir hosts. These spirochetes have evolved several surface proteins to manipulate rodent host immunity, some of which remain polymorphic in Borrelia populations. Among these proteins, OspE, which binds the host complement-regulating factor CFH to evade destruction by complement, is one of the most variable. Yet, what evolutionary forces maintain this polymorphism is not well understood. Motivated by a recent discovery of CFH polymorphism in the bank vole (Clethrionomys glareolus), the main reservoir host of B. afzelii, we hypothesized that the polymorphism is maintained by host-parasite coevolution involving specific associations between host and parasite genetic variants. MethodsWe analyzed associations between bank vole CFH alleles and B. afzelii OspE variants across three datasets sampled in Poland. Selection acting on OspE was evaluated using omegaMap. Host-pathogen genotype associations were tested using partial redundancy analysis (RDA), and co-structure was assessed using co-correspondence analysis (CoCA). ResultsWe found that OspE evolves under positive selection, however, we found no evidence for an association between OspE and host CFH variants at the individual level based on RDA or at the population level based on CoCA. ConclusionsDespite evidence of positive selection acting on OspE, we found no support for specific genetic matching between B. afzelii and its bank vole host at the CFH-OspE interface. These results suggest that the evolution of CFH and OspE may be shaped by broader selective pressures, potentially including interactions with multiple host species.

Understanding spatial and temporal connectivity among individuals with different migration strategies is essential for migratory ecology and effective conservation, yet it often requires integrating multiple data sources. In Northeast Atlantic European sea bass (Dicentrarchus labrax), electronic tagging has revealed partial migration, with both resident and long-distance migrants showing fidelity to summer feeding and winter spawning areas. However, the role of regional spawning-site philopatry in shaping migration patterns and stock connectivity remains unclear. Here, we combine reconstructed migration trajectories with genome-wide analyses of gene flow and recent relatedness in 708 individuals sampled from 10 French Atlantic locations. We identify a seasonally shifting genetic discontinuity between the Bay of Biscay (BOB) and Northern (NS) stocks, located off western Brittany during winter spawning and displaced northeastward into the central English Channel during summer feeding. Despite seasonal mixing in the English Channel, an association between individual genetic composition and spawning-site selection supports regional spawning-site philopatry. Analyses of long genomic segments shared identical-by-descent reveal substantially greater connectivity within stocks than between stocks, indicating that philopatry constrains effective gene flow despite seasonal mixing. Reanalysis of independent genomic data further shows that sea bass from the northern Atlantic range predominantly belong to the Northern stock. Together, these results show how seasonal movements reshape spatial genetic structure while maintaining demographic subdivision, with direct implications for fisheries management.

The global study of freshwater clams in the genus Corbicula is frequently confounded by invasive androgenetic lineages that experience mitochondrial DNA capture and clonal propagation. In contrast, the endemic Corbicula of Sulawesi's ancient lakes reproduce sexually, offering a uniquely reliable system for mitochondrial population genetics. This study provides the first population-genetic framework for two endemic species, Corbicula possoensis (Lake Poso) and C. linduensis (Lake Lindu), using the cytochrome c oxidase subunit I (COI) marker. We analysed 90 newly generated COI sequences from C. possoensis (six stations) and C. linduensis (three stations), integrated with reference sequences from GenBank, to assess genetic diversity, population structure, and phylogeographic patterns. Hierarchical AMOVA revealed deep divergence between the two lakes ({Phi}_CT = 0.607), consistent with prolonged independent isolation rather than a single shared vicariance event, as the two species do not form a sister pair in the phylogeny. Within Lake Poso, C. possoensis exhibited exceptionally high genetic diversity (24 haplotypes; h = 0.876; {pi} = 0.016) and pronounced micro-geographic structuring into three phylogeographic zones (North: Tentena and Siuri; East: Tando Nceppo and Busogo Beach; Southwest: Bancea and Pendolo), each characterised by distinct haplogroups. Remarkably, the maximum divergence between zones (K2P = 2.33%) approached the interspecific distance between C. possoensis and C. linduensis (K2P = 2.42%), indicating that within-lake mitochondrial divergence has reached near-interspecific levels. Conversely, C. linduensis displayed near-panmixia and extreme genetic depauperation (3 haplotypes; h = 0.246; {pi} = 0.0004), indicating long-term demographic stasis within a restricted habitat. The deep phylogeographic zonation in C. possoensis suggests that its discrete populations should be treated as separate Management Units (MUs) in conservation planning to preserve locally adapted gene complexes, whereas the severely depauperate gene pool of C. linduensis renders it critically vulnerable to environmental disturbance and invasive species, warranting urgent IUCN Red List assessment. To validate these mitochondrial boundaries and inform future conservation strategies, multi-marker and genome-wide reassessments are strongly recommended.

The coast redwood (Sequoia sempervirens) is a long-lived, hexaploid conifer of high ecological, cultural, and economic value whose range has been greatly reduced by historical logging. Effective restoration and conservation depend on understanding patterns of genetic differentiation across the redwood range to delineate populations for management prioritization. Yet, past range-wide studies provided only a partial picture of population structure in coast redwood as they relied on a limited set of genetic markers or limited sampling, as sequencing was done on the same range-wide provenance collection. Here, we analyze 334,029 SNPs from a new range-wide set of 224 individuals using a dosage-based approach that accounts for polyploidy. Principal coordinates and neighbor-joining analyses reveal clear latitudinal genetic differentiation, with a distinct break south of San Francisco Bay. Outlier SNP analysis indicates new candidate loci involved in salinity tolerance, climate stress response, and nutrient uptake, suggesting potential local adaptation. These results point to the central role of geography in shaping genetic variation in coast redwood and give scientific basis for designing new conservation strategies and future experiments, including assisted migration, provenance trials, and restoration planning aimed at preserving the species into the future.

Understanding the genetic structure of keystone species within river networks is essential for effective conservation and management. While population differentiation of anadromous species often occurs between river systems, less research has been conducted on differentiation within rivers with smaller catchment areas. In this study, we investigated the population genetic structure of wild Atlantic salmon (Salmo salar) across the small-scale river Ronne [a] system in southernmost Sweden using Restriction-site Associated DNA sequencing (RADseq). Although the Admixture analysis did not detect clearly defined genetic clusters, significant pairwise FST values and DAPC revealed emerging population differentiation among the Ronne [a] tributaries. The observed patterns are consistent with a system characterized by connectivity, where genetic flow is present but can be reduced by behavioral and ecological factors such as spawning homing behavior and selective movements. These findings suggest that, despite overall connectivity, Atlantic salmon populations in the Ronne [a] catchment area may function as partially independent sub-populations. This highlights the importance of conservation and management strategies in fragmented river systems to consider population genetic structure to support resilient salmon populations under ongoing anthropogenic pressures.

Japanese chum salmon supported by one of the world largest hatchery programs have experienced severe declines in marine survival and egg size. To investigate the underlying mechanisms, we analyzed a 21-year time series (1999-2019) of reproductive traits of age-4 chum salmon from 13 rivers together with climate and salmon abundance data using a bootstrap-supported Bayesian network. Here, we assumed that environmental variables can affect the chum salmon populations, but not vice versa, and that there could be maternal effect on reproductive traits, but not the other way around. These constraints enabled us to infer the causal links that shaped the biogeography of North Pacific chum salmon. Global warming caused a decline in Japanese chum salmon abundance, resulting in the increase of the competing Russian chum, which in turn decreased the female body size, fecundity, and egg size of Japanese chum. These findings suggest that climate-driven warming may have exposed genetic effects of hatchery practices, contributing to fitness decline in Japanese chum salmon and the ecological reorganization of chum salmon populations in the North Pacific.

The unprecedented rate of climate warming threatens many species, and assessing their vulnerability to climate change represents a critical challenge in conservation biology. The Apollo butterfly, an emblematic mountain species, is expected to be impacted by climate change. Here, we analysed thousands of SNPs from 101 localities across Apollo French distribution. We identified 93 SNPs strongly associated with climate variation using five genotype-environment association analyses. We forecasted future climate maladaptation of French Apollo populations using four genomic offset methods and integrated these results with neutral and adaptive genetic diversity, genetic structure and adaptive climatic niches to infer their vulnerability to climate change. Jura and Alps populations exhibited the lowest risk of vulnerability to climate change, with low genomic offsets, high genetic diversity and connectivity, whereas Auvergne populations showed the highest genomic offsets and lowest neutral and adaptive genetic diversity. Only a reduced percentage (<1%) of the current distribution is predicted to face climatic conditions outside the current range, suggesting that adaptive variability required to adapt to future climates may already be present, and that assisted gene flow could represent an effective conservation strategy. Finally, we discuss some of the main challenges of genomic forecasts, particularly for declining non-model species.

Biological invasions on islands provide a natural framework to study how dispersal and connectivity influence evolutionary and ecological processes. The avian nest parasitic fly, Philornis downsi - first recorded in Darwin's finch nests in 1997 - causes high mortality in endemic land birds, yet its inter-island and sex-specific patterns of dispersal and genetic structure remain poorly understood. We use low-coverage whole genome sequencing to investigate genome-wide patterns of genetic diversity, directional migration and effective population size in P. downsi across five major Galapagos Islands and its native range in mainland Ecuador. We find evidence for a genetic bottleneck in the Galapagos, isolation by distance, and evidence that the island closest to the Ecuadorian mainland, San Cristobal, is genetically divergent from the other four islands sampled, despite retaining the highest genetic diversity. No evidence was found for sex-biased dispersal; however, sex-biased genetic structure was detected using only markers from inferred autosomal scaffolds. We found asymmetric gene flow with higher migration rates from San Cristobal westward to the other islands, matching the direction of both southeast trade winds and major cargo shipping routes. Our results suggest both natural and human-mediated colonisation of P. downsi from the mainland through San Cristobal to the other islands, followed by high inter-island dispersal among closely situated sink islands. Our findings are critical for prioritising islands for control strategies that will reduce P. downsi impacts on vulnerable endemic birds and underscore the value of understanding directional migration patterns for managing invasive species in metapopulations.

A core aim of ex situ conservation is to represent wild genetic diversity in managed living collections. For the climate-threatened tropical montane cloud forest (TMCF) flora of northeast Australia, an ex situ metacollection of plants and seeds has been established by the Tropical Mountain Plant Science (TroMPS) project. In this study we used reduced-representation sequencing (DArTseq) of wild, herbarium, and ex situ material alongside provenance information for ten species, to pursue two central aims: to characterise landscape-scale genetic structure across species' ranges, and to evaluate how well the assembled metacollections represent that wild diversity. Analyses revealed consistent patterns of genetic differentiation among mountain top populations across multiple species, reflecting the isolating influence of lowland gaps between upland habitats, with the degree of differentiation varying among species. These results provide the first genetic baseline for Australian TMCF flora and reinforce the importance of treating individual mountain top populations as distinct units for conservation management. Additionally, the project provided valuable insights into the logistical challenges of coordinated multi-institutional collecting, informing strategies for metacollection design more broadly. Evaluation of the metacollection revealed both strengths and gaps in representation across species, providing an evidence base to refine the current holdings and guide future targeted collecting to strengthen their long-term conservation value.

Knowledge regarding variation in habitat use among individuals is crucial for understanding population dynamics and for management and conservation measures. This is especially important for diadromous fishes that shift between habitats, being affected by external pressures and environmental change in different habitats over ontogeny. Herer, we assessed individual variation in habitat use of European eel along a salinity gradient, ranging from fully marine to freshwater in northern Europe, using otolith microchemistry data from >3600 eel together with established time-series segmentation and clustering methods. We show that eel display high degree of individual variation in habitat use. Assigned life-histories included coastal resident, freshwater resident, and coastal and freshwater habitat shifting individuals. Coastal resident eels were observed in a large range of salinities. Given the widespread occurrence of migration barriers in freshwater, it is unknown whether the coastal resident eel preferred that habitat, or if it was the only available habitat for them. Our findings nonetheless highlight the need to include coastal habitats when assessing population development and silver eel production of the critically endangered European eel.

Homing endonuclease genes spread by cleaving homologous chromosomes that lack the endonuclease cassette, after which repair from the endonuclease-containing chromosome converts the cut allele into a copy of the drive allele. This mechanism has provided a conceptual foundation for synthetic gene drive systems, including CRISPR-based drives, that represent promising strategies for the genetic control of insect pests. However gene drive performance depends critically on the repair pathways available in the germline of the target organism. Here, we report a set of transgenic assays originally developed as part of an attempt to establish gene targeting in the malaria mosquito Anopheles gambiae using an in vivo-generated linear targeting molecule. Although the intended FLP-mediated excision step was not achieved in the mosquito germline, analysis of the component strains revealed efficient germline activity of the rare-cutting homing endonuclease I-SceI and a striking bias towards homology-based repair of I-SceI-induced double-strand breaks. Across reporter and donor configurations, cleavage outcomes were dominated by single-strand annealing, microhomology-mediated repair, synthesis-dependent strand annealing and gene conversion-like events, with comparatively limited evidence for classical non-homologous end joining. In reciprocal crosses designed to distinguish gene conversion from gamete loss, I-SceI cleavage also produced inheritance distortion consistent with both conversion of the cleaved allele and reduced recovery of gametes carrying extensively damaged donor alleles. These findings indicate that the An. gambiae germline can strongly favour homology-dependent repair following homing endonuclease cleavage and that cleavage can also generate meiotic drive-like distortion through selective loss of damaged gametes. The results have direct relevance for the design and interpretation of homing endonuclease and CRISPR-based gene drives in malaria mosquitoes, where the balance between homology-directed repair, end joining and gamete viability will determine drive efficiency, resistance formation and transmission bias. Author summaryGene drives depend on a simple but demanding principle: a nuclease cuts one chromosome, and the cell repairs the break using the homologous chromosome as a template, copying the drive element in the process. Before CRISPR, this type of system was explored using naturally occurring homing endonucleases such as I-SceI. We attempted to develop a gene targeting system in Anopheles gambiae based on the Rong and Golic strategy, in which FLP recombinase would excise a donor molecule and I-SceI would linearise it to stimulate recombination. The full knockout technology did not work because FLP-mediated excision was not detected in the mosquito germline. However, the component tests revealed something more broadly important: I-SceI-induced breaks were repaired predominantly through homology-based pathways rather than simple end joining. We also observed inheritance distortion consistent with both gene conversion and loss of damaged gametes. These results help explain why homing-based systems can work in mosquitoes, while also highlighting why repair pathway choice and gamete viability need to be measured directly in any new drive configuration.

Invasive ambrosia beetles and fungal pathogens threaten forest ecosystems worldwide, exemplified in Hawaii by the widespread loss of keystone species [o]hia (Metrosideros polymorpha), due to Rapid [O]hia Death (ROD). A unique occurrence of five ambrosia beetle species (one native, four introduced) that vary in their symbiotic relationships with two introduced fungal pathogens provide an opportunity to test hypotheses of how opportunistic symbioses facilitate disease dynamics involving dominant forest trees. ROD is caused by two novel Ceratocystis fungal pathogens whose spores can spread via association with ambrosia beetles as they bore into [o]hia trees. We examined beetle-pathogen interactions of all five ambrosia beetle species in three ROD-affected regions on Hawaii Island, and used quantitative PCR (qPCR) to provide the first molecular confirmation of the two ROD pathogens associated with the exterior, mycangia, and gut of each beetle species. Results from generalized linear models and correlation networks show that pathogen acquisition and transport, including the potential for consumption and the presence of the pathogens, are determined by beetle invasion status and mycangia morphology. A niche construction framework suggests that both varying symbioses and opportunism facilitate disease spread, with the three invasive Xyleborus species emerging as key disease vectors. Identifying the beetle species that are more likely to contribute to disease spread, and understanding their biology as vectors, can inform targeted conservation strategies for [o]hia and for insect-pathogen threats in forests worldwide, and illustrates the potential ecosystem-level impacts of novel and opportunistic symbioses between globally distributed invasive vectors and pathogens.

Bacterial leaf blight (BB), caused by Xanthomonas oryzae pv. oryzae (Xoo), causes yield losses exceeding 50% in affected areas, including the Bagre rice plain in Burkina Faso. Genome-edited (GEd) rice lines have been successful in tackling BB. Modifications in the Xoo virulence protein target site upstream of three SWEET susceptibility genes in two elite rice varieties, IR64 and Ciherang-Sub1, have been demonstrated to confer broad-spectrum resistance to Asian and East African Xoo strains. Here, we evaluate the potential of the GEd lines as a solution for BB management in Burkina Faso. We challenged the GEd lines against five locally collected Burkinabe Xoo strains under controlled green-house conditions and assessed their agro-morphological performance under field conditions representative of local agroecological conditions. Greenhouse pathogen assays demonstrated that GEd IR64 and Ciherang-Sub1 lines were resistant to all tested local Xoo strains across three successive generations. We identified TalC as the primary disease-causing effector in the local Xoo populations. Irrigated field trials conducted over two seasons in the Kou Valley, Burkina Faso, revealed absence of agro-morphological penalties in GEd lines compared to their parental wild-type lines. Observed trait variation was attributable to environmental fluctuations rather than genomic modifications. Collectively, our findings demonstrate that genome editing of the rice lines does not impose growth penalties, and support the suitability of GEd IR64 and Ciherang-Sub1 for large-scale adoption in Burkina Faso, pending multi-location validation and introgression into locally adapted varieties.

The global invasion of the Asian tiger mosquito Aedes albopictus has led to an increase in arboviral disease, including within Mesoamerica. Understanding vector invasion routes is important for public health because it directs biosecurity and identifies sources of adaptive allele spread. Panama is an important hub of global trade with opportunities for Aedes introduction through both maritime and overland routes but dispersal into the Isthmus has not yet been investigated. We therefore sought to investigate the population structure and invasion history of Ae. albopictus into Panama, targeting both its mitogenome and associated Wolbachia. Historical demographic analysis with Bayesian phylogeographic diffusion models and estimates of divergence revealed that Panamanian Ae. albopictus and its associated Wolbachia have a convergent evolutionary history resulting from multiple introductions. Both could be traced to Asian-derived lineages introduced via the Americas, with invasion primarily through the maritime trade of the Panama Canal rather than overland dispersal from neighboring Costa Rica. An investigation of the relative density of Wolbachia in Panama revealed that both the strains wAlbB and wAlbA were at a notably lower density compared to other worldwide locations. This finding has implications for arbovirus transmission and raises important questions about how Wolbachia density is impacted by the environment and impacts on population control. Overall, the Panama Canal is a key route for vector introductions into Mesoamerica.

Aedes aegypti is a major vector of arboviruses, and belongs to subfamily Culicinae, a diverse group of mosquitoes with homomorphic sex-determining chromosomes. Males are the heterogametic sex with a dominant male-determining locus (M locus). The M locus and its counterpart m locus are embedded in a region of suppressed recombination, with a large portion of this recombination desert showing significant molecular differentiation despite homomorphy. We developed a mathematical framework to examine M-linked genome editors that specifically target the m-chromosome during spermatogenesis, mimicking the naturally occurring sex ratio distorters (SRDs) in Culicinae that produce male-biased meiotic drives. Unlike previous models for species with heteromorphic sex chromosomes (e.g., X and Y), we incorporate features stemming from the homomorphic nature of the Ae. aegypti sex chromosomes such as varied linkage to the M locus, making the degree of super-Mendelian inheritance readily tunable. We evaluated in silico SRDs with a range of M-linkage and editing efficiencies and established the theoretical foundation for developing highly efficient SRDs that outperform several methods of population suppression. These SRDs can be tuned to mitigate impact on a neighboring population. The framework developed here is suitable for exploring SRD-mediated genetic biocontrol of pests with homomorphic sex chromosomes.