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It is often claimed that genes affecting health in old age, such as cardiovascular and Alzheimer diseases, are beyond the reach of natural selection. We show in a simulation study based on known genetic (apolipoprotein E) and non-genetic risk factors (gender, diet, smoking, alcohol, exercise) that, because there is a statistical distribution of ages at which these genes exert their influence on morbidity and mortality, the effects of selection are in fact non-negligible. A gradual increase with each generation of the  ε2  and  ε3  alleles of the gene at the expense of the  ε4  allele was predicted from the model. The  ε2  allele frequency was found to increase slightly more rapidly than that for  ε3 , although there was no statistically significant difference between the two. Our result may explain the recent evolutionary history of the epsilon 2, 3 and 4 alleles of the apolipoprotein E gene and has wider relevance for genes affecting human longevity.

Selection on Alleles Affecting Human Longevity and Late-Life Disease: The Example of Apolipoprotein E