How much does the unguarded X contribute to sex differences in life span?

Abstract

Females and males often have markedly different mortality rates and life spans, but it is unclear why these forms of sexual dimorphism evolve. The unguarded X hypothesis contends that dimorphic life spans arise from sex differences in X or Z chromosome copy number (i.e., one copy in the "heterogametic" sex; two copies in the "homogametic" sex), which leads to a disproportionate expression of deleterious mutations by the heterogametic sex (e.g., mammalian males; avian females). Although data on adult sex ratios and sex-specific longevity are consistent with predictions of the unguarded X hypothesis, direct experimental evidence remains scant, and alternative explanations are difficult to rule out. Using a simple population genetic model, we show that the unguarded X effect on sex differential mortality is a function of several reasonably well-studied evolutionary parameters, including the proportion of the genome that is sex linked, the genomic deleterious mutation rate, the mean dominance of deleterious mutations, the relative rates of mutation and strengths of selection in each sex, and the average effect of mutations on survival and longevity relative to their effects on fitness. We review published estimates of these parameters, parameterize our model with them, and show that unguarded X effects are too small to explain observed sex differences in life span across species. For example, sex differences in mean life span are known to often exceed 20% (e.g., in mammals), whereas our parameterized models predict unguarded X effects of a few percent (e.g., 1-3% in Drosophila and mammals). Indeed, these predicted unguarded X effects fall below statistical thresholds of detectability in most experiments, potentially explaining why direct tests of the hypothesis have generated little support for it. Our results suggest that evolution of sexually dimorphic life spans is predominantly attributable to other mechanisms, potentially including "toxic Y" effects and sexual dimorphism for optimal investment in survival versus reproduction.

Keywords: Deleterious mutations; evolution of life span; evolutionary theory; inbreeding depression; population genetics; sex chromosomes; sex ratio; sexual dimorphism.

Figure 1

Curated published estimates of species‐specific sex‐biased mutation rates, expressed as the ratio of male to female rates ($R_{\mu }={\overline{\mu }}_m/{\overline{\mu }}_f$). Results were compiled by surveying the primary literature, including preprints (for details, see the main text and the Supporting Information). We focused on the subset of estimates in which sex‐biased mutation rates could be calculated for individual species or species lineages rather than groups of related species. In cases where there were multiple estimates for a species, we took the average (we excluded a single outlier of $R_{\mu }\sim 20$ from humans; Wilson Sayres et al. 2011). This process yielded a total of 118 species‐specific estimates (numbers per species group are shown in the figure) from 29 studies (17 mammal, six bird, six other). The vertical broken lines denote equal rates of mutation between the sexes ($R_{\mu }=1$); values exceeding one are male biased $(R_{\mu }>1;{\overline{\mu }}_m>{\overline{\mu }}_f)$.

Figure 2

Unguarded X effects in species with mammalian‐like, Drosophila‐like, and bird‐like sex chromosomes. Results are shown for plausible values of the haploid genomic deleterious mutation rate (U_H  = 1.1 for vertebrates, based on a relatively high estimate from humans: Keightley ; Dukler et al. ; U_H  = 0.5 for Drosophila: Haag‐Liautard et al. 2007), with typical sex chromosome sizes for mammals, flies, and birds (bird results are based on the upper end of range of Z chromosome sizes: 0.07 < P_Z  < 0.1; Stiglec et al. ; Sultanova et al. 2020), and equally strong purifying selection in each sex (β = 1). The gray‐shaded regions correspond to the range of $\overline{\alpha }$ estimates obtained from Drosophila studies ($0.1<\overline{\alpha }<0.3$; Charlesworth 2015), and the orange lines correspond to dominance values consistent with both theory and mutation accumulation studies from model organisms ($\overline{h}=0.25$; see Manna et al. 2011).