Genetic constraints underlying human reproductive timing in a premodern Swiss village

The trade-off between reproductive investment in early versus late life is central to life-history theory. Despite abundant empirical evidence supporting different versions of this trade-off, the specific trade-off between age at first reproduction (AFR) and age at last reproduction (ALR) has received little attention, especially in long-lived species with a pronounced reproductive senescence such as humans. Using genealogical data for a 19th-century Swiss village, we (i) quantify natural selection acting on reproductive timing, (ii) estimate the underlying additive genetic (co)variances, and (iii) use these to predict evolutionary responses. Selection gradients were computed using multiple linear regression, and the additive genetic variance-covariance matrix was estimated using a restricted maximum-likelihood animal model. We found strong selection for both an early AFR and a late ALR, which resulted from selection for an earlier and longer reproductive period (RP, i.e., ALR-AFR). Furthermore, postponing AFR shortened RP in both sexes, but twice as much in women. Finally, AFR and ALR were strongly and positively genetically correlated, which led to a considerable reduction in the predicted responses to selection, or even rendered them maladaptive. These results provide evidence for strong genetic constraints underlying reproductive timing in humans, which may have contributed to the evolution of menopause.