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

Abstract

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. Impact Summary Females and males are dimorphic for a wide range of traits, including the average lengths of their life spans. Sex differences in life span are both conspicuous and variable among species. For example, in mammals, females live ∼20% longer than males (on average), whereas in birds, males live ∼10% longer than females. One leading explanation for these patterns—the unguarded X hypothesis—argues that sex differences in life span emerge from the distinct sex chromosomes that females and males inherit. For many species, one sex (e.g., female mammals; male birds) carries two copies of each X-linked gene, whereas the other carries one. Because harmful mutations are partially recessive, the sex with only one copy of the X is more prone to expressing them, and that sex should therefore have a shorter average life span. This prediction of the unguarded X hypothesis is qualitatively consistent with observations of sex-ratio bias in adults and sexual dimorphism for longevity (e.g., mammalian males have one copy of the X and have shorter lives than females). However, there are other possible explanations for these patterns, making it unclear how much the unguarded X explains species diversity for sex-specific longevity. We developed a mathematical model for the contribution of unguarded X effects to sex differences in survival and life span, and used data on mutation rates and their effects on survival and fitness to quantify the importance of the unguarded X across species. The model, when combined with current data, suggests that the unguarded X hypothesis cannot explain the conspicuous sex differences in life span that are commonly reported in animal species, particularly vertebrates. Our results suggest that the unguarded X is an unlikely general explanation for the evolution of sexually dimorphic life spans, which gives weight to alternative mechanisms, including “toxic Y” effects and sex differential selection via trade-offs between survival and reproduction.