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.

21 Unravelling Transmission Ratio Distortion Across the Genome of a Crossbreed Beef Cattle Population

Transmission ratio distortion (TRD) is a process when one allele from either parent is preferentially transmitted to the offspring. The identification of genomic regions affected by TRD might help in the detection of lethal alleles or potential genes affecting reproduction. Here, we investigated TRD in crossbreed beef cattle population aiming to identify genomic regions showing altered deviations in segregation that could be affecting reproduction performance. A total of 237 genotyped animals were used including 46 sires, 80 dams, and 111 parent-offspring (trios). The predominant breeds of these animals were Angus (61.83%), Simmental (18.99%), Gelbvieh (6.12%), Charolais (3.65%), Hereford (2.46%) and Limousin (1.57%). After excluding SNPs with minor allele frequency lower than 0.05 and call-rate lower than 0.90, a total of 369,902 autosomal SNPs were retained for further analyses. The SNP-by-SNP analysis was performed within a Bayesian framework using TRDscanv.2.0 software, using 100,000 iterations, with 10,000 iterations being discarded as burn-in. As table 1 shows, 33 SNPs were identified with TRD, considering a Bayes Factor (BF)≥100 and the approximate empirical null distribution of TRD at 0.01% margin error. Among them, 26 SNPs were parent-unspecific and 7 SNPs were parent-specific TRD. For parent-specific TRD, 214 were identified for sire- and 162 for dam-TRD (BF≥100). Among them, 4 SNPs were detected with sire- and dam-TRD in opposite direction of preference of transmission. Preliminary functional and positional analysis was performed using the list of TRD regions with BF≥100 and the approximate empirical null distribution of TRD at 0.01% margin error. For sire-TRD, 14% of the identified QTL (n = 254) were related to non-return rate. For dam-TRD, 21 regions related to conception rate were found (1.5%) and 13 regions related to stillbirth (0.93%). Haplotype analysis is in progress to identify additional candidate regions and alleles with TRD to better understand this phenomenon in a crossbreed beef population.

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.

Does degeneration or genetic conflict shape gene content on UV sex chromosomes?

Studies of sex chromosomes have played a central role in understanding the consequences of suppressed recombination and sex-specific inheritance among several genomic phenomena. However, we argue that these efforts will benefit from a more rigorous examination of haploid UV sex chromosome systems, in which both the female-limited (U) and male-limited (V) experience suppressed recombination and sex-limited inheritance, and both are transcriptionally active in the haploid and diploid states. We review the life cycle differences that generate UV sex chromosomes and genomic data showing that ancient UV systems have evolved independently in many eukaryotic groups, but gene movement on and off the sex chromosomes, and potentially degeneration continue to shape the current gene content of the U and V chromosomes. Although both theory and empirical data show that the evolution of UV sex chromosomes is shaped by many of the same processes that govern diploid sex chromosome systems, we highlight how the symmetrical inheritance between the UV chromosomes provide an important test of sex-limited inheritance in shaping genome architecture. We conclude by examining how genetic conflict (over sexual dimorphism, transmission-ratio distortion, or parent-offspring conflict) may drive gene gain on UV sex chromosomes, and highlight the role of breeding system in governing the action of these processes. Collectively these observations demonstrate the potential for evolutionary genomic analyses of varied UV sex chromosome systems, combined with natural history studies, to understand how genetic conflict shapes sex chromosome gene content.

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.

Impact of SNP calling quality on the detection of transmission ratio distortion in goats

Transmission ratio distortion (TRD) is the preferential transmission of one specific allele to offspring at the expense of the other one. The existence of TRD is mostly explained by the segregation of genetic variants with deleterious effects on the developmental processes that go from the formation of gametes to fecundation and birth. A few years ago, a statistical methodology was implemented in order to detect TRD signals on a genome-wide scale as a first step to uncover the biological basis of TRD and reproductive success in domestic species. In the current work, we have analyzed the impact of SNP calling quality on the detection of TRD signals in a population of Murciano-Granadina goats. Seventeen bucks and their offspring (N=288) were typed with the Goat SNP50 BeadChip, while the genotypes of the dams were lacking. Performance of a genome-wide scan revealed the existence of 36 SNPs showing significant evidence of TRD. When we calculated GenTrain scores for each one of the SNPs, we observed that 25 SNPs showed scores below 0.8. The allele frequencies of these SNPs in the offspring were not correlated with the allele frequencies estimated in the dams with statistical methods, thus evidencing that flawed SNP calling quality might lead to the detection of spurious TRD signals. We conclude that, when performing TRD scans, the GenTrain scores of markers should be taken into account to discriminate SNPs that are truly under TRD from those yielding spurious signals due to technical problems.

Genetic Mapping of the Gamete Eliminator Locus, S2, Causing Hybrid Sterility and Transmission Ratio Distortion Found between Oryza sativa and Oryza glaberrima Cross Combination

Hybrid sterility is a reproductive barrier that prevents gene flow between species. In Oryza species, some hybrid sterility loci, which are classified as gamete eliminators, cause pollen and seed sterility and sex-independent transmission ratio distortion (siTRD) in hybrids. However, the molecular basis of siTRD has not been fully characterized because of lacking information on causative genes. Here, we analyze one of the hybrid sterility loci, S2, which was reported more than forty years ago but has not been located on rice chromosomes. Hybrids between African rice (Oryza glaberrima) and a near-isogenic line that possesses introgressed chromosomal segments from Asian rice (Oryza sativa) showed sterility and siTRD, which confirms the presence of the S2 locus. Genome-wide SNP marker survey revealed that the near-isogenic line has an introgression on chromosome 4. Further substitution mapping located the S2 locus between 22.60 Mb and 23.54 Mb on this chromosome. Significant TRD in this chromosomal region was also observed in a calli population derived from cultured anther in hybrids of another cross combination of African and Asian rice species. This indicates that the pollen abortion caused by the S2 locus occurs before callus induction in anther culture. It also suggests the wide existence of the S2-mediated siTRD in this interspecific cross combination. Chromosomal location of the S2 locus will be valuable for identifying causative genes and for understanding of the molecular basis of siTRD.

Within-trio tests provide little support for post-copulatory selection on major histocompatibility complex haplotypes in a free-living population

Sexual selection has been proposed as a force that could help maintain the diversity of major histocompatibility complex (MHC) genes in vertebrates. Potential selective mechanisms can be divided into pre-copulatory and post-copulatory, and in both cases, the evidence for occurrence is mixed, especially in natural populations. In this study, we used a large number of parent-offspring trios that were diplotyped for MHC class II genes in a wild population of Soay sheep ( Ovis aries ) to examine whether there was within-trio post-copulatory selection on MHC class II genes at both the haplotype and diplotype levels. We found there was transmission ratio distortion of one of the eight MHC class II haplotypes (E) which was transmitted less than expected by fathers, and transmission ratio distortion of another haplotype (A) which was transmitted more than expected by chance to male offspring. However, in both cases, these deviations were not significant after correction for multiple tests. In addition, we did not find any evidence of post-copulatory selection at the diplotype level. These results imply that, given known parents, there is no strong post-copulatory selection on MHC class II genes in this population.