Sex differences in deleterious mutational effects in Drosophila melanogaster: combining quantitative and population genetic insights

Abstract

Abstract Fitness effects of deleterious mutations can differ between females and males due to: (i) sex differences in the strength of purifying selection; and (ii) sex differences in ploidy. Although sex differences in fitness effects have important broader implications (e.g., for the evolution of sex and lifespan), few studies have quantified their scope. Those that have belong to one of two distinct empirical traditions: (i) quantitative genetics, which focusses on multi-locus genetic variances in each sex, but is largely agnostic about their genetic basis; and (ii) molecular population genetics, which focusses on comparing autosomal and X-linked polymorphism, but is poorly suited for inferring contemporary sex differences. Here, we combine both traditions to present a comprehensive analysis of female and male adult reproductive fitness among 202 outbred, laboratory-adapted, hemiclonal genomes of Drosophila melanogaster. While we find no clear evidence for sex differences in the strength of purifying selection, sex differences in ploidy generate multiple signals of enhanced purifying selection for X-linked loci. These signals are present in quantitative genetic metrics—i.e., a disproportionate contribution of the X to male (but not female) fitness variation—and population genetic metrics—i.e., steeper regressions of an allele’s average fitness effect on its frequency, and proportionally less nonsynonymous polymorphism on the X than autosomes. Fitting our data to models for both sets of metrics, we infer that deleterious alleles are partially recessive. Given the often-large gap between quantitative and population genetic estimates of evolutionary parameters, our study showcases the benefits of combining genomic and fitness data when estimating such parameters.