Secular changes in sexual and natural selection against deleterious genetic mutations in humans

Abstract

All genetic variation once arose by mutation. Genetic variation is the substance on which natural selection can act, but mutations are random. Therefore, new variations usually have negative or no effects on an organism’s evolutionary fitness. This dissertation is not about the exciting exceptions to this rule, which drive evolutionary adaptation, but about harmful mutations. We know that the average human child is born with 70-100 genetic variants that its parents did not carry, around 2.2 of which are estimated to be harmful. Why don't these harmful mutations build up irreversibly? Natural and sexual selection may have continuously worked against harmful mutations building up, but do they still? Geneticists commonly worry that human civilisation has sheltered us from the purifying selection against mutations by reducing infant mortality, introducing modern medicine, social transfers, and the like. In this work, I studied whether we can find evidence of changes in purifying selection by examining the relationship between paternal age, an index of de novo mutations, and evolutionary fitness in four large cohorts from before and after the industrial revolution and more than 1.4 million people. We find no evidence for such changes, in so far as paternal age effects are a useful index, nor do we find that contemporary fathers are unprecedentedly old and hence a bigger source of mutations. In a second study, we tested whether the hormonal contraceptive pill interferes with evolutionarily adapted shifts in mate preferences across the menstrual cycle. Although we find changes in sexual desire and behaviour across the menstrual cycle in women who do not use the pill, we find no evidence of changed mate preferences. Our research cannot allay worries about relaxed selection, delayed reproduction, and altered mate choices, but we report evidence that, given proper context and empirical comparisons, these changes do not seem drastic. The balance between mutation and selection may not be as fragile as some have predicted, but it is clearly a topic worth examining. We call for further careful and empirical examination of this topic and the many other factors that may affect strength and efficacy of selection.