Sex-Specific Selection and Sex-Biased Gene Expression in Humans and Flies

Abstract

Sexual dimorphism results from sex-biased gene expression, which evolves when selection acts differently on males and females. While there is an intimate connection between sex-biased gene expression and sex-specific selection, few empirical studies have studied this relationship directly. Here we compare the two on a genome-wide scale in humans and flies. We find a distinctive “Twin Peaks” pattern in humans that relates the strength of sex-specific selection, quantified by genetic divergence between male and female adults at autosomal loci, to the degree of sex-biased expression. Genes with intermediate degrees of sex-biased expression show evidence of ongoing sex-specific selection, while genes with either little or completely sex-biased expression do not. This pattern apparently results from differential viability selection in males and females acting in the current generation. The Twin Peaks pattern is also found in Drosophila using a different measure of sex-specific selection acting on fertility. We develop a simple model that successfully recapitulates the Twin Peaks. Our results suggest that many genes with intermediate sex-biased expression experience ongoing sex-specific selection in humans and flies.

Population genetics of sexual conflict in the genomic era

“…Sex-biased genes are typically thought to represent largely resolved sexual conflict over optimal expression (Box 2) 10,26,45 , however one study 25 found that moderately sex-biased genes showed elevated FST in humans. This observation suggests that loci with intermediate However, inter-sexual genetic differentiation alone cannot distinguish loci subject to sexual conflict over survival from loci where sexual conflict has been resolved through the evolution of separate genetic architecture [46][47][48] (Fig.…”

“…Preliminary 29 and published studies 25,38,40,41 of sexual conflict have measured nucleotide diversity with Tajima's D (Box 2), which estimates the proportion of nucleotide sites in a given sequence that are polymorphic within a population. This approach is based on the assumption that balancing selection from sexual conflict will lead to the maintenance of multiple alleles, which will in turn cause higher than expected levels of sequence diversity compared to regions not under balancing selection.…”

“…However, two recent studies have used one such measure, the fixation index (FST), to assess the extent of allelic differentiation between males and females in a population 18,25 . Importantly, allele frequency is identical between the sexes at conception before selection acts because it is defined at the start of each generation by Hardy-Weinberg equilibrium based on the allele frequency of the parental population.…”

“…It is worth noting that if genetic differentiation between females and males is the product of sexual conflict over adult survival or mortality (for example, from differential predation) the age of the samples could have an important influence on FST estimates. However, if sexual conflict occurs over viability and embryonic lethality, it is sufficient to sample individuals that have survived until birth (or eclosion in the case of insects).Sex-biased genes are typically thought to represent largely resolved sexual conflict over optimal expression (Box 2) 10,26,45 , however one study 25 found that moderately sex-biased genes showed elevated FST in humans. This observation suggests that loci with intermediate However, inter-sexual genetic differentiation alone cannot distinguish loci subject to sexual conflict over survival from loci where sexual conflict has been resolved through the evolution of separate genetic architecture [46][47][48] (Fig.…”

“…For example, previous evidence suggested that sexual conflict is primarily the result of an allele increasing the reproductive fitness of one sex at some cost to the other [14][15][16] . However, more recent studies point to the potential for sexual conflict over viability or survival, where an allele increases the likelihood that one sex will live long enough to reproduce at some cost to the other 17,18, 25 . Published [25][26][27][28] and preliminary 29 studies have also sparked new debate, for example, about how often and how quickly sexual conflict can be resolved.…”