title: Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.
abstract: 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 epsilon2 and epsilon3 alleles of the gene at the expense of the epsilon4 allele was predicted from the model. The epsilon2 allele frequency was found to increase slightly more rapidly than that for epsilon3, 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.
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle Upon Tyne, Tyne, United Kingdom. F.Drenos@ucl.ac.uk
authors.forename: Fotios
authors.initials: F
authors.lastname: Drenos
authors.forename: Thomas B L
authors.initials: TB
authors.lastname: Kirkwood
mesh_terms: D017677:Age Distribution; D000367:Age Factors; D000483:Alleles; D053329:Apolipoprotein E2 / Q000235:genetics / Q000502:physiology; D053318:Apolipoprotein E3 / Q000235:genetics / Q000502:physiology; D053327:Apolipoprotein E4 / Q000235:genetics / Q000502:physiology; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology; D003198:Computer Simulation; D019143:Evolution, Molecular; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008957:Models, Genetic; D012641:Selection, Genetic
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E