The search for sexually antagonistic genes: Practical insights from studies of local adaptation and statistical genomics

Abstract

Sexually antagonistic (SA) genetic variation-in which alleles favored in one sex are disfavored in the other-is predicted to be common and has been documented in several animal and plant populations, yet we currently know little about its pervasiveness among species or its population genetic basis. Recent applications of genomics in studies of SA genetic variation have highlighted considerable methodological challenges to the identification and characterization of SA genes, raising questions about the feasibility of genomic approaches for inferring SA selection. The related fields of local adaptation and statistical genomics have previously dealt with similar challenges, and lessons from these disciplines can therefore help overcome current difficulties in applying genomics to study SA genetic variation. Here, we integrate theoretical and analytical concepts from local adaptation and statistical genomics research-including F ST and F IS statistics, genome-wide association studies, pedigree analyses, reciprocal transplant studies, and evolve-and-resequence experiments-to evaluate methods for identifying SA genes and genome-wide signals of SA genetic variation. We begin by developing theoretical models for between-sex F ST and F IS , including explicit null distributions for each statistic, and using them to critically evaluate putative multilocus signals of sex-specific selection in previously published datasets. We then highlight new statistics that address some of the limitations of F ST and F IS , along with applications of more direct approaches for characterizing SA genetic variation, which incorporate explicit fitness measurements. We finish by presenting practical guidelines for the validation and evolutionary analysis of candidate SA genes and discussing promising empirical systems for future work.

Sex-Specific Selection Drives the Evolution of Alternative Splicing in Birds

“…Recent theoretical work has indicated that patterns of elevated intersexual differentiation previously observed in the literature that have been attributed to ongoing sexual conflict would require implausibly large selective pressures and mortality loads ( Kasimatis et al. 2017 , 2019 , 2020 ; Ruzicka et al. 2020 ).…”

Is the X chromosome a hot spot for sexually antagonistic polymorphisms? Biases in current empirical tests of classical theory

“…To bridge the gap between theoretical predictions and empirical metrics of SA variation, we have merged and extended three independent strands of prior theory: (i) population genetic models of SA polymorphism [27,28,30,32], (ii) quantitative genetic models of sex-specific fitness (co)variance [72][73][74], and (iii) models of between-sex F ST estimates [46]. To set clear empirical benchmarks for testing Rice's hypothesis, we have derived predictions for what empiricists might expect to observe in cases where the X and autosomes are equally permissive locations for SA polymorphism.…”

“…Sex differences in selection generate allele frequency differences between the female and male gametes that give rise to offspring of the next generation, with fertilized eggs or ovules enriched for female-beneficial alleles, and fertilizing sperm or pollen enriched for male-beneficial alleles [57]. Allele frequencies are often estimated from samples of the adults of a population, and estimates of between-sex F ST may indirectly reflect sex differences in viability selection (reviewed in [45,46]).…”

“…In practice, F ST,i is calculated using allele frequency estimates from samples of adults, in which case, estimated allele frequency differences between sexes reflect actual allele frequency differences in the population as well as statistical noise associated with allele frequency estimation (see [46]). Accounting for both effects, the expected F ST,i estimates for an autosomal and X-linked locus (respectively) are:…”

“…Finally, Lucotte et al [44] showed that estimates of allele frequency differences between adult human females and males (i.e. 'intersexual F ST ' estimates) are elevated on the X compared with autosomes, which may imply an enrichment of SA polymorphisms on the human X due to sex differences in viability selection [45,46].…”