Evolutionary demographic models reveal the strength of purifying selection on susceptibility alleles to late-onset diseases.
Résumé
Geneticists have long considered alleles involved in post-menopause mortality to be neutral as no reproduction occurs anymore. Population genetics models have predicted that genetic drift rather than purifying selection was shaping the allelic spectrum of late-onset diseases, leading to a few common variants explaining most of the diseases’ prevalences. However, recent association studies show that most susceptibility alleles to late onset diseases have low frequencies: a characteristic of alleles under negative selection. We show that susceptibility alleles to late onset diseases are under purifying selection for most known age-at-onset distributions of late-onset genetic diseases. We conclude that neutrality is probably the exception among alleles that have a deleterious effect in old age and that accounting for sociocultural factors is required to understand the full extent of the force of selection shaping senescence in humans.