Do Sex Ratio Distorting Microbes Inhibit the Evolution of Pesticide Resistance? An Experimental Test.

We are still largely reliant on pesticides for the suppression of arthropod pests which threaten human health and food production, but the recent rise of evolved resistance among important pest species has reduced pesticide efficacy. Despite this, our understanding of strategies that effectively limit the evolution of resistance remains weak. Male-killing sex ratio distorting microbes (SRDMs), such as Wolbachia and Spiroplasma, are common among arthropod species. Previous theoretical work has suggested that they could limit adaptive potential in two ways: first, because by distorting sex ratios they reduce the effective population size, and second, because infected females produce no male offspring which restricts gene flow. Here we present the results of a novel experiment in which we test the extent by which these two mechanisms limit the adaptive response of arthropods to pesticide. Using a fully factorial design, we manipulated the adult sex ratio of laboratory populations of Drosophila melanogaster, both in the presence and absence of SRDMs, and exposed these populations to six generations of pesticide poisoning. This design allows the effects of SRDMs on sex ratio and their effects on gene flow to be estimated separately. After six generations, individuals from populations with even sex ratios displayed a higher resistance to pesticide relative to individuals from female-biased populations. By contrast, we found no effect of the presence of SRDMs in host populations on pesticide resistance independent of sex ratio. In addition, males were more susceptible to pesticide than females-this was true of flies from both naïve and previously exposed populations. These findings provide the first empirical proof of concept that sex ratio distortion arising from SRDMs can limit adaptation to pesticides, but cast doubt on the theoretical effect of male-killers limiting adaptation by disrupting gene flow.

Virtually delivered cognitive behavioural therapy for avoidant restrictive food intake disorder (CBT-AR): a case study in an adult with elevated autistic traits.

Cognitive Behavioural Therapy for Avoidant and Restrictive Food Intake Disorder (CBT-AR; ARIFD) is a psychological treatment that targets many of the core symptoms of ARFID. Although a growing literature supports the efficacy of behavioural interventions for paediatric feeding and eating disorders, including ARFID, the applicability of these methods to adults remains undetermined. Telehealth delivery of CBT-AR in adults with autism has yet to be tested. With this study, we conduct a preliminary evaluation of CBT-AR delivered virtually to a 26-year-old white British female, with mixed ARFID and elevated autistic traits. She attended 23 remote CBT-AR sessions facilitated through a dedicated telehealth platform. Adjustments were made to accommodate her lived experience of neurodiversity. Using a pre-post treatment design, changes on measures of subjective goal attainment, eating-related and general psychosocial impairment, general anxiety, and depression were evaluated. Following treatment, the participant had made significant progress towards personally meaningful goals, with improvements observed in nutritional intake, general well-being, and reductions in eating-related psychosocial impairment and general anxiety. The results offer preliminary insights into acceptability and efficacy of virtual CBT-AR for neurodiverse individuals.

Sex ratio distorting microbes exacerbate arthropod extinction risk in variable environments.

Maternally-inherited sex ratio distorting microbes (SRDMs) are common among arthropod species. Typically, these microbes cause female-biased sex ratios in host broods, either by; killing male offspring, feminising male offspring, or inducing parthenogenesis. As a result, infected populations can experience drastic ecological and evolutionary change. The mechanism by which SRDMs operate is likely to alter their impact on host evolutionary ecology; despite this, the current literature is heavily biased towards a single mechanism of sex ratio distortion, male-killing. Furthermore, amidst the growing concerns surrounding the loss of arthropod diversity, research into the impact of SRDMs on the viability of arthropod populations is generally lacking. In this study, using a theoretical approach, we model the epidemiology of an understudied mechanism of microbially-induced sex ratio distortion-feminisation-to ask an understudied question-how do SRDMs impact extinction risk in a changing environment? We constructed an individual-based model and measured host population extinction risk under various environmental and epidemiological scenarios. We also used our model to identify the precise mechanism modulating extinction. We find that the presence of feminisers increases host population extinction risk, an effect that is exacerbated in highly variable environments. We also identified transmission rate as the dominant epidemiological trait responsible for driving extinction. Finally, our model shows that sex ratio skew is the mechanism driving extinction. We highlight feminisers and, more broadly, SRDMs as important determinants of the resilience of arthropod populations to environmental change.

Systematic approaches to assessing high-temperature limits to fertility in animals.

Critical thermal limits (CTLs) gauge the physiological impact of temperature on survival or critical biological function, aiding predictions of species range shifts and climatic resilience. Two recent Drosophila species studies, using similar approaches to determine temperatures that induce sterility (thermal fertility limits [TFLs]), reveal that TFLs are often lower than CTLs and that TFLs better predict both current species distributions and extinction probability. Moreover, many studies show fertility is more sensitive at less extreme temperatures than survival (thermal sensitivity of fertility [TSF]). These results present a more pessimistic outlook on the consequences of climate change. However, unlike CTLs, TFL data are limited to Drosophila, and variability in TSF methods poses challenges in predicting species responses to increasing temperature. To address these data and methodological gaps, we propose 3 standardized approaches for assessing thermal impacts on fertility. We focus on adult obligate sexual terrestrial invertebrates but also provide modifications for other animal groups and life-history stages. We first outline a "gold-standard" protocol for determining TFLs, focussing on the effects of short-term heat shocks and simulating more frequent extreme heat events predicted by climate models. As this approach may be difficult to apply to some organisms, we then provide a standardized TSF protocol. Finally, we provide a framework to quantify fertility loss in response to extreme heat events in nature, given the limitations in laboratory approaches. Applying these standardized approaches across many taxa, similar to CTLs, will allow robust tests of the impact of fertility loss on species responses to increasing temperatures.

The suppression of a selfish genetic element increases a male's mating success in a fly.

X chromosome meiotic drive (XCMD) kills Y-bearing sperm during spermatogenesis, leading to the biased transmission of the selfish X chromosome. Despite this strong transmission, some natural XCMD systems remain at low and stable frequencies, rather than rapidly spreading through populations. The reason may be that male carriers can have reduced fitness, as they lose half of their sperm, only produce daughters, and may carry deleterious alleles associated with XCMD. Thus, females may benefit from avoiding mating with male carriers, yielding a further reduction in fitness. Genetic suppressors of XCMD, which block the killing of Y sperm and restore fair Mendelian inheritance, are also common and could prevent the spread of XCMD. However, whether suppressed males are as fit as a wild-type male remains an open question, as the effect that genetic suppressors may have on a male's mating success is rarely considered. Here, we investigate the mating ability of XCMD males and suppressed XCMD males in comparison to wild-type males in the fruit fly Drosophila subobscura, where drive remains at a stable frequency of 20% in wild populations where it occurs. We use both competitive and non-competitive mating trials to evaluate male mating success in this system. We found no evidence that unsuppressed XCMD males were discriminated against. Remarkably, however, their suppressed XCMD counterparts had a higher male mating success compared to wild-type controls. Unsuppressed XCMD males suffered 12% lower offspring production in comparison to wild-type males. This cost appears too weak to counter the transmission advantage of XCMD, and thus the factors preventing the spread of XCMD remain unclear.

The effect of short-term exposure to high temperatures on male courtship behaviour and mating success in the fruit fly Drosophila virilis.

Human-induced climate change is leading to higher average global temperatures and increasingly extreme weather events. High temperatures can have obvious effects on animal survival, particularly in ectotherms. However, the temperature at which organisms become sterile may be significantly lower than the temperature at which other biological functions are impaired. In the fruit fly Drosophila virilis, males are sterilized at temperatures above 34 °C, but are still active and able to mate normally. We investigated the male behavioural changes associated with high-temperature fertility loss. We exposed males to a warming treatment of 34.4 °C or 36.6 °C for 4 h, and then recorded their mating behaviour after being allowed to recover for 24 h. Previous work in this species suggests that males exposed to 34.4 °C lose the ability to produce new sperm, but can utilize mature sperm produced before the heat shock. We therefore predicted that these males would increases their courtship rate, and reduce their choosiness, in order to try to ensure a mating before their remaining mature sperm die. In contrast, over two-thirds of males exposed to 36.6 °C are completely sterile. In standard mating trials, earlier exposure to 34.4 °C or 36.6 °C did not affect male courtship behaviour when compared to control males kept at 23 °C. Exposure to high temperatures also did not alter the extent to which males directed courtship toward females of the same species. However, males exposed to 36.6 °C were significantly slower to mate, and had a reduced likelihood of mating, when compared to control males. Overall, exposure to high temperatures did not alter male courtship behaviour, but did lower their likelihood of mating. This suggests that females can distinguish between normal and heat-sterilized males before mating, and that female mate choice may at least partly mitigate the population-level consequences of high-temperature induced male sterility in this species.

The United Kingdom Eating Disorders Genetics Initiative.

OBJECTIVE: The United Kingdom Eating Disorders Genetics Initiative (EDGI UK), part of the National Institute for Health and Care Research (NIHR) Mental Health BioResource, aims to deepen our understanding of the environmental and genetic etiology of eating disorders. EDGI UK launched in February 2020 and is partnered with the UK eating disorders charity, Beat. Multiple EDGI branches exist worldwide. This article serves the dual function of providing an in-depth description of our study protocol and of describing our initial sample including demographics, diagnoses, and physical and psychiatric comorbidities. METHOD: EDGI UK recruits via media and clinical services. Anyone living in England, at least 16 years old, with a lifetime probable or clinical eating disorder is eligible to sign up online: edgiuk.org. Participants complete online questionnaires, donate a saliva sample for genetic analysis, and consent to medical record linkage and recontact for future studies. RESULTS: As of September 2022, EDGI UK recruited 7435 survey participants: 98% female, 93.1% white, 97.8% cisgender, 65.9% heterosexual, and 52.1% have a university degree. Over half (57.8%) of these participants have returned their saliva DNA kit. The most common diagnoses are anorexia nervosa (48.3%), purging disorder (37.8%), bulimia nervosa (37.5%), binge-eating disorder (15.8%), and atypical anorexia nervosa (7.8%). CONCLUSION: EDGI UK is the largest UK eating disorders study and efforts to increase its diversity are underway. It offers a unique opportunity to accelerate eating disorder research. Researchers and participants with lived experience can collaborate on projects with unparalleled sample size. PUBLIC SIGNIFICANCE STATEMENT: Eating disorders are debilitating and costly for society but are under-researched due to underfunding. EDGI UK is one of the largest eating disorder studies worldwide with ongoing recruitment. The collected data constitute a resource for secondary analysis. We will combine data from all international EDGI branches and the NIHR BioResource to facilitate research that improves our understanding of eating disorders and their comorbidities.

Levels of P-element-induced hybrid dysgenesis in Drosophila simulans are uncorrelated with levels of P-element piRNAs.

Transposable elements (TEs) are genomic parasites that proliferate within host genomes, and which can also invade new species. The P-element, a DNA-based TE, recently invaded two Drosophila species: Drosophila melanogaster in the 20th century, and D. simulans in the 21st. In both species, lines collected before the invasion are susceptible to "hybrid dysgenesis", a syndrome of abnormal phenotypes apparently due to P-element-inflicted DNA damage. In D. melanogaster, lines collected after the invasion have evolved a maternally acting mechanism that suppresses hybrid dysgenesis, with extensive work showing that PIWI-interacting small RNAs (piRNAs) are a key factor in this suppression. Most of these studies use lines collected many generations after the initial P-element invasion. Here, we study D. simulans collected early, as well as late in the P-element invasion of this species. Like D. melanogaster, D. simulans from late in the invasion show strong resistance to hybrid dysgenesis and abundant P-element-derived piRNAs. Lines collected early in the invasion, however, show substantial variation in how much they suffer from hybrid dysgenesis, with some lines highly resistant. Surprisingly, although, these resistant lines do not show high levels of cognate maternal P-element piRNAs; in these lines, it may be that other mechanisms suppress hybrid dysgenesis.

Female fruit flies cannot protect stored sperm from high temperature damage.

Recently, it has been demonstrated that heat-induced male sterility is likely to shape population persistence as climate change progresses. However, an under-explored possibility is that females may be able to successfully store and preserve sperm at temperatures that sterilise males, which could ameliorate the impact of male infertility on populations. Here, we test whether females from two fruit fly species can protect stored sperm from a high temperature stress. We find that sperm carried by female Drosophila virilis are almost completely sterilised by high temperatures, whereas sperm carried by female Zaprionus indianus show only slightly reduced fertility. Heat-shocked D. virilis females can recover fertility when allowed to remate, suggesting that the delivered heat-shock is damaging stored sperm and not directly damaging females in this species. The temperatures required to reduce fertility of mated females are substantially lower than the temperatures required to damage mature sperm in males, suggesting that females are worse than males at protecting mature sperm. This suggests that female sperm storage is unlikely to ameliorate the impacts of high temperature fertility losses in males, and instead exacerbates fertility costs of high temperatures, representing an important determinant of population persistence during climate change.

The impact of female mating strategies on the success of insect control technologies.

Attempts to control insect pests and disease vectors have a long history. Recently, new technology has opened a whole new range of possible methods to suppress or transform natural populations. But it has also become clear that a better understanding of the ecology of targeted populations is needed. One key parameter is mating behaviour. Often modified males are released which need to successfully reproduce with females while competing with wild males. Insect control techniques can be affected by target species' mating ecology, and conversely mating ecology is likely to evolve in response to manipulation attempts. A better understanding of (female) mating behaviour will help anticipate and overcome potential challenges, and thus make desirable outcomes more likely.

Plastic responses of survival and fertility following heat stress in pupal and adult Drosophila virilis.

The impact of rising global temperatures on survival and reproduction is putting many species at risk of extinction. In particular, it has recently been shown that thermal effects on reproduction, especially limits to male fertility, can underpin species distributions in insects. However, the physiological factors influencing fertility at high temperatures are poorly understood. Key factors that affect somatic thermal tolerance such as hardening, the ability to phenotypically increase thermal tolerance after a mild heat shock, and the differential impact of temperature on different life stages are largely unexplored for thermal fertility tolerance. Here, we examine the impact of high temperatures on male fertility in the cosmopolitan fruit fly Drosophila virilis. We first determined whether temperature stress at either the pupal or adult life history stage impacts fertility. We then tested the capacity for heat-hardening to mitigate heat-induced sterility. We found that thermal stress reduces fertility in different ways in pupae and adults. Pupal heat stress delays sexual maturity, whereas males heated as adults can reproduce initially following heat stress, but become sterile within seven days. We also found evidence that while heat-hardening in D. virilis can improve high temperature survival, there is no significant protective impact of this same hardening treatment on fertility. These results suggest that males may be unable to prevent the costs of high temperature stress on fertility through heat-hardening, which limits a species' ability to quickly and effectively reduce fertility loss in the face of short-term high temperature events.

The application of rapid evaporative ionization mass spectrometry in the analysis of Drosophila species-a potential new tool in entomology.

There is increasing emphasis on the use of new analytical approaches in subject analysis and classification, particularly in respect to minimal sample preparation. Here, we demonstrate that rapid evaporative ionization mass spectrometry (REIMS), a method that captures metabolite mass spectra after rapid combustive degradation of an intact biological specimen, generates informative mass spectra from several arthropods, and more specifically, is capable of discerning differences between species and sex of several adult Drosophila species. A model including five Drosophila species, built using pattern recognition, achieves high correct classification rates (over 90%) using test datasets and is able to resolve closely related species. The ease of discrimination of male and female specimens also demonstrates that sex-specific differences reside in the REIMS metabolite patterns, whether analysed across all five species or specifically for D. melanogaster. Further, the same approach can correctly discriminate and assign Drosophila species at the larval stage, where these are morphologically highly similar or identical. REIMS offers a novel approach to insect typing and analysis, requiring a few seconds of data acquisition per sample and has considerable potential as a new tool for the field biologist.

Selfish genetic elements and male fertility.

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'.

Resistance to natural and synthetic gene drive systems.

Scientists are rapidly developing synthetic gene drive elements intended for release into natural populations. These are intended to control or eradicate disease vectors and pests, or to spread useful traits through wild populations for disease control or conservation purposes. However, a crucial problem for gene drives is the evolution of resistance against them, preventing their spread. Understanding the mechanisms by which populations might evolve resistance is essential for engineering effective gene drive systems. This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in general.

Sexual function and dysfunction among women with anorexia nervosa: A systematic scoping review.

OBJECTIVE: Research suggests that a variety of biological and psychosocial factors are associated with the sexual health of women diagnosed with anorexia nervosa (AN). This systematic scoping review, conducted in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, synthesizes the current literature concerning sexual function and dysfunction in women with AN. METHOD: We searched PubMed, EMBASE, and PsychInfo for literature published until April 2020. All study designs were eligible for inclusion, providing they focused on sexual function and dysfunction in women with AN. Studies that only included outcomes related to gender identity or sexual orientation were excluded. RESULTS: N = 28 studies met criteria for inclusion in the review. All studies were conducted in Western countries and the majority employed either a cohort or cross-sectional design. Although measures of sexual function and dysfunction varied markedly across studies, most studies adopted a biopsychosocial framework. Libido may be linked to body mass index (BMI), while other aspects of sexual functioning and behavior might not be specifically associated with weight status. Limited data are available on evidence-based interventions. DISCUSSION: Sexual dysfunction in women with AN is common. Although some of the variance is explained by low BMI, associated physiological sequelae and other psychosocial factors are also involved. Sexual dysfunction is a relevant clinical problem and clinicians should sensitively incorporate questions related to sexual function into their eating disorder assessments. Future research, using more robust designs and validated outcome measures, is needed to better understand causal pathways between the biological and psychosocial correlates of AN and sexual dysfunction. Identifying predictors of sexual function and dysfunction in more diverse groups of people with AN will support the development of evidence-based therapies.

OBJETIVO: La investigación sugiere que una variedad de factores biológicos y psicosociales están asociados con la salud sexual de las mujeres diagnosticadas con anorexia nervosa (AN). Esta revisión exploratoria sistemática, realizada de acuerdo con las Directrices PRISMA, sintetiza la literatura actual sobre la función y la disfunción sexual en mujeres con AN. MÉTODOS: Se realizaron búsquedas en PubMed, EMBASE y PsychInfo para la literatura publicada hasta abril de 2020. Todos los diseños de estudio fueron elegibles para su inclusión, siempre que se centraran en la función y la disfunción sexual en mujeres con AN. Se excluyeron los estudios que solo incluyeron resultados relacionados con la identidad de género u orientación sexual. RESULTADOS: Un total de N = 28 estudios cumplieron los criterios para su inclusión en la revisión. Todos los estudios se realizaron en países occidentales y la mayoría empleó un diseño de cohorte o transversal. Aunque las medidas de la función y la disfunción sexual variaron notablemente entre los estudios, la mayoría de los estudios adoptaron un marco biopsicosocial. La líbido puede estar relacionada con el IMC, mientras que otros aspectos del funcionamiento y el comportamiento sexual pueden no estar específicamente asociados con el estado de peso corporal. Se dispone de datos limitados sobre intervenciones basadas en evidencia. DISCUSIÓN: La disfunción sexual en mujeres con AN es común y plantea un problema clínico relevante. Aunque parte de la varianza se explica por el bajo IMC y las secuelas fisiológicas asociadas, otros factores psicosociales también están involucrados. Se necesitan investigaciones futuras, que usen diseños más robustos y medidas de resultado validadas, para comprender mejor las vías causales entre los correlatos biológicos y psicosociales de la AN y la disfunción sexual. La identificación de predictores de la función y la disfunción sexual en grupos más diversos de personas con AN apoyará el desarrollo de terapias basadas en la evidencia.

Mate-finding Allee effects can be exacerbated or relieved by sexual cannibalism.

Allee effects occur when individual or population survival decreases due to populations being small or sparse. A key mechanism underlying Allee effects is difficulty in finding mates at low densities. Species may be particularly vulnerable to mate-finding Allee effects if females rely on an abundance of males to reproduce successfully. In sexually cannibalistic species, females may consume males before or after copulation, potentially reducing the supply of males to the point where a mate-finding Allee effect occurs. In this study, we investigate the extent to which sexual cannibalism can modulate mate-finding Allee effects, and the conditions under which sexual cannibalism is likely to be particularly detrimental to population viability. We created an individual-based model that tracked specific females throughout the breeding season and used extinction risk and per capita growth rate to measure the strength of the Allee effects. We varied both founder population size and mate encounter rate independently of each other to expose the mechanism driving the Allee effects. We also analysed how cannibalism-derived female fecundity benefits affected extinction risk. We found that sexual cannibalism could lead to high extinction risk, particularly when cannibalism occurred before copulation, founder population size was small and mate encounter rates were low. However, post-copulatory cannibalism reduced extinction risk, if cannibalism increased female fecundity enough. We found that there were strong threshold effects, in which small changes in encounter rate could strongly alter population extinction risk. We find that sexual cannibalism is likely to negatively impact population survival as population size and mate encounter rate decrease. This may be exacerbated if male quality declines and female hunger increases in declining populations. As many top invertebrate predators, such as spiders and mantises, are sexually cannibalistic, this may have ecosystem-wide impacts. We also suggest that other reproductive behaviours, such as rejecting all but high-quality mates or requiring multiple mates to ensure fertility, are also likely to cause mate-finding Allee effects when habitat quality degrades.

Cognitive remediation for inpatients with psychosis: a systematic review and meta-analysis.

Cognitive difficulties are common in people with psychosis and associated with considerable disability. Cognitive remediation (CR) can reduce the burden of cognitive difficulties and improve functioning. While mental health care has predominantly shifted to the community, people with greater illness severity and complexity, and those with poor response to treatment and concomitant greater cognitive difficulties, continue to receive inpatient care. The aim of this study is to review and evaluate the acceptability and efficacy of CR for inpatients with psychosis. A systematic search was used to identify randomized controlled trials of CR for inpatients with psychosis. Demographic and clinical information was extracted by independent raters together with therapy outcomes. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Standardized mean change for cognitive and functional outcomes was calculated using Hedges's g and used to infer therapy effects with meta-analysis. Twenty studies were identified considering 1509 participants. Results from random-effect models suggested that CR was effective in improving processing speed (g = 0.48), memory (g = 0.48) and working memory (g = 0.56). While there was an indication of improvements in the levels of vocational, social and global functioning, these were less reliable. On average, 7% of participants dropped-out of treatment. Studies methodological quality was moderate. CR is an acceptable intervention for inpatients with psychosis and can lead to significant cognitive improvements. Evidence for improvement in functioning requires more robust and converging evidence. Future research should extend the evaluation of inpatient CR to subsequent post-discharge community functioning and further need for care.

Drosophila Sexual Attractiveness in Older Males Is Mediated by Their Microbiota.

Age is well known to be a basis for female preference of males. However, the mechanisms underlying age-based choices are not well understood, with several competing theories and little consensus. The idea that the microbiota can affect host mate choice is gaining traction, and in this study we examine whether the male microbiota influences female preference for older individuals in the fruit fly Drosophila pseudoobscura. We find that an intact microbiota is a key component of attractiveness in older males. However, we found no evidence that this decrease in older male attractiveness was simply due to impaired microbiota generally reducing male quality. Instead, we suggest that the microbiota underlies an honest signal used by females to assess male age, and that impaired microbiota disrupt this signal. This suggests that age-based preferences may break down in environments where the microbiota is impaired, for example when individuals are exposed to naturally occurring antibiotics, extreme temperatures, or in animals reared in laboratories on antibiotic supplemented diet.

An X-linked meiotic drive allele has strong, recessive fitness costs in female Drosophila pseudoobscura.

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.