The Potential for a Released Autosomal X-Shredder Becoming a Driving-Y Chromosome and Invasively Suppressing Wild Populations of Malaria Mosquitoes

Sex-ratio distorters based on X-chromosome shredding are more efficient than sterile male releases for population suppression. X-shredding is a form of sex distortion that skews spermatogenesis of XY males towards the preferential transmission of Y-bearing gametes, resulting in a higher fraction of sons than daughters. Strains harboring X-shredders on autosomes were first developed in the malaria mosquito Anopheles gambiae, resulting in strong sex-ratio distortion. Since autosomal X-shredders are transmitted in a Mendelian fashion and can be selected against, their frequency in the population declines once releases are halted. However, unintended transfer of X-shredders to the Y-chromosome could produce an invasive meiotic drive element, that benefits from its biased transmission to the predominant male-biased offspring and its effective shielding from female negative selection. Indeed, linkage to the Y-chromosome of an active X-shredder instigated the development of the nuclease-based X-shredding system. Here, we analyze mechanisms whereby an autosomal X-shredder could become unintentionally Y-linked after release by evaluating the stability of an established X-shredder strain that is being considered for release, exploring its potential for remobilization in laboratory and wild-type genomes of An. gambiae and provide data regarding expression on the mosquito Y-chromosome. Our data suggest that an invasive X-shredder resulting from a post-release movement of such autosomal transgenes onto the Y-chromosome is unlikely.

Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population

In species with single-locus, chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, and are not mediated by random maternal effects. SRD exhibits a heritable component, but QTL mapping analyses fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We explore several potential complex genetic mechanisms for SRD, including allelic interactions leading to sex-biased lethality, genetic sex reversal, chromosome drive mediated by sex-linked selfish elements, and incompatibilities between specific maternal and paternal genotypes. We show that no one mechanism offers a singular explanation for this population-wide SRD. Instead, our data present preliminary evidence for the action of distinct mechanisms of SRD at play in different strains. Taken together, our work exposes the pervasiveness of SRD in the CC population and nominates the CC as a powerful resource for investigating diverse genetic causes of biased sex chromosome transmission.

Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population

In species with single-locus chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, are not fully mediated by maternal effects, and are not explained by sex-biased neonatal mortality. SRD exhibits a heritable component, but QTL mapping analyses and targeted investigations of sex determination genes fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We speculate that the genetic shuffling of eight diverse parental genomes during the early CC breeding generations led to the decoupling of sex-linked drivers from their co-evolved suppressors, unleashing complex, multiallelic systems of sex chromosome drive. Consistent with this interpretation, we show that several CC strains exhibit copy number imbalances at co-evolved X- and Y-linked ampliconic genes that have been previously implicated in germline genetic conflict and SRD in house mice. Overall, our findings reveal the pervasiveness of SRD in the CC population and nominate the CC as a powerful resource for investigating sex chromosome genetic conflict in action.

Sex Ratios in a Warming World: Thermal Effects on Sex-Biased Survival, Sex Determination, and Sex Reversal

Rising global temperatures threaten to disrupt population sex ratios, which can in turn cause mate shortages, reduce population growth and adaptive potential, and increase extinction risk, particularly when ratios are male biased. Sex ratio distortion can then have cascading effects across other species and even ecosystems. Our understanding of the problem is limited by how often studies measure temperature effects in both sexes. To address this, the current review surveyed 194 published studies of heat tolerance, finding that the majority did not even mention the sex of the individuals used, with <10% reporting results for males and females separately. Although the data are incomplete, this review assessed phylogenetic patterns of thermally induced sex ratio bias for 3 different mechanisms: sex-biased heat tolerance, temperature-dependent sex determination (TSD), and temperature-induced sex reversal. For sex-biased heat tolerance, documented examples span a large taxonomic range including arthropods, chordates, protists, and plants. Here, superior heat tolerance is more common in females than males, but the direction of tolerance appears to be phylogenetically fluid, perhaps due to the large number of contributing factors. For TSD, well-documented examples are limited to reptiles, where high temperature usually favors females, and fishes, where high temperature consistently favors males. For temperature-induced sex reversal, unambiguous cases are again limited to vertebrates, and high temperature usually favors males in fishes and amphibians, with mixed effects in reptiles. There is urgent need for further work on the full taxonomic extent of temperature-induced sex ratio distortion, including joint effects of the multiple contributing mechanisms.

Transmission, Tropism, and Biological Impacts of Torix Rickettsia in the Common Bed Bug Cimex lectularius (Hemiptera: Cimicidae)

The torix group of Rickettsia have been recorded from a wide assemblage of invertebrates, but details of transmission and biological impacts on the host have rarely been established. The common bed bug (Cimex lectularius) is a hemipteran insect which lives as an obligatory hematophagous pest of humans and is host to a primary Wolbachia symbiont and two facultative symbionts, a BEV-like symbiont, and a torix group Rickettsia. In this study, we first note the presence of a single Rickettsia strain in multiple laboratory bed bug isolates derived from Europe and Africa. Importantly, we discovered that the Rickettsia has segregated in two laboratory strains, providing infected and uninfected isogenic lines for study. Crosses with these lines established transmission was purely maternal. Fluorescence in-situ hybridization analysis indicates Rickettsia infection in oocytes, bacteriomes, and other somatic tissues. We found no evidence that Rickettsia infection was associated with sex ratio distortion activity, but Rickettsia infected individuals developed from first instar to adult more slowly. The impact of Rickettsia on fecundity and fertility resulted in infected females producing fewer fertile eggs. However, we could not find any evidence for cytoplasmic incompatibility associated with Rickettsia presence. These data imply the existence of an unknown benefit to C. lectularius carrying Rickettsia that awaits further research.

Transmission, tropism and biological impacts of torix Rickettsia in the common bed bug Cimex lectularius (Hemiptera: Cimicidae)

ABSTRACTThe torix group of Rickettsia have been recorded from a wide assemblage of invertebrates, but details of transmission and biological impacts on the host have rarely been established. The common bed bug (Cimex lectularius) is a hemipteran insect which lives as an obligatory hematophagous pest of humans and is host to a primary Wolbachia symbiont and two facultative symbionts, a BEV-like symbiont, and a torix group Rickettsia. In this study, we first note the presence of a single Rickettsia strain in multiple laboratory bed bug isolates derived from Europe and Africa. Importantly, we discovered that the Rickettsia has segregated in two laboratory strains, providing infected and uninfected isogenic lines for this study. Crosses with these lines established transmission was purely maternal, in contrast to previous studies of torix infections in planthoppers where paternal infection status was also important. Fluorescence in-situ hybridization analysis indicates Rickettsia infected in oocytes and bacteriomes, and other somatic tissues. There was no evidence that Rickettsia infection was associated with sex ratio distortion activity, but Rickettsia infected individuals developed from first instar to adult more slowly. The impact of Rickettsia on fecundity and fertility were investigated. Rickettsia infected females produced fewer fertile eggs, but there was no evidence for cytoplasmic incompatibility. These data imply the existence of an unknown benefit to C. lectularius carrying Rickettsia that awaits further research.

Environmental Influences on Crustacean Sex Determination and Reproduction: Environmental Sex Determination, Parasitism, and Pollution

This chapter reviews the influences of environmental factors on sex determination, sex ratios, and reproductive behavior in the Crustacea, focusing in particular on amphipod and isopod examples. A range of abiotic and biotic environmental factors influence reproduction in Crustacea, including temperature, day length, pollutants, and parasites. Individual crustaceans may benefit from these environmental influences, but in other cases, reproductive biology responses to biotic and abiotic environments may be detrimental to individual fitness. Environmental Sex Determination (ESD) falls into the former category. ESD is an adaptive mechanism of sex determination that is rare, but has evolved in diverse taxa. Evidence from gammarid amphipods is used to explore the evolution of ESD in response to a patchy environment. While ESD is an adaptive mechanism of sex determination, the impact of other environmental factors can be very costly. Parasitic castrators can lead to a reduction or total cessation of reproduction in crustacean hosts, driving population declines. In contrast, parasitic feminizers convert male hosts into females, enhancing maternal parasite transmission but also leading to sex ratio distortion in the host population. The chapter discusses parasite-host coevolutionary conflict and reviews evidence that selection on the host in response to parasitic sex ratio distortion has led to altered mate choice in amphipods, and to the evolution of a novel system of sex determination in isopods. Human-induced environmental influences can also be seen in Crustacea, and the chapter discusses how parasites, ESD, and endocrine-disrupting chemicals can each affect sex determination and lead to abnormal intersex phenotypes. It ends by highlighting areas for future research on the diverse world of crustacean reproduction.

Battle of the Sex Chromosomes: Competition between X and Y Chromosome-Encoded Proteins for Partner Interaction and Chromatin Occupancy Drives Multicopy Gene Expression and Evolution in Muroid Rodents

Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs, which have been coamplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict in which each favors its own transmission, resulting in sex ratio distortion of the progeny when Slx/Slxl1 versus Sly copy number is unbalanced. They are specifically expressed in male postmeiotic gametes (spermatids) and have opposite effects on gene expression: Sly knockdown leads to the upregulation of hundreds of spermatid-expressed genes, whereas Slx/Slxl1-deficiency downregulates them. When both Slx/Slxl1 and Sly are knocked down, sex ratio distortion and gene deregulation are corrected. Slx/Slxl1 and Sly are, therefore, in competition but the molecular mechanism remains unknown. By comparing their chromatin-binding profiles and protein partners, we show that SLX/SLXL1 and SLY proteins compete for interaction with H3K4me3-reader SSTY1 (Spermiogenesis-specific-transcript-on-the-Y1) at the promoter of thousands of genes to drive their expression, and that the opposite effect they have on gene expression is mediated by different abilities to recruit SMRT/N-Cor transcriptional complex. Their target genes are predominantly spermatid-specific multicopy genes encoded by the sex chromosomes and the autosomal Speer/Takusan. Many of them have coamplified with not only Slx/Slxl1/Sly but also Ssty during muroid rodent evolution. Overall, we identify Ssty as a key element of the X versus Y intragenomic conflict, which may have influenced gene content and hybrid sterility beyond Mus lineage since Ssty amplification on the Y predated that of Slx/Slxl1/Sly.