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

Lookup NU author(s): Fotios Drenos, Emeritus Professor Thomas Kirkwood



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 epsilon 2 and epsilon 3 alleles of the gene at the expense of the epsilon 4 allele was predicted from the model. The epsilon 2 allele frequency was found to increase slightly more rapidly than that for epsilon 3, 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.

Publication metadata

Author(s): Drenos F, Kirkwood TBL

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2010

Volume: 5

Issue: 3

Print publication date: 01/04/2010

Date deposited: 21/05/2010

ISSN (print):

ISSN (electronic): 1932-6203

Publisher: Public Library of Science


DOI: 10.1371/journal.pone.0010022


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