selection on alleles affecting human longevity and late-life disease the example of apolipoprotein e选择在等位基因影响人类长寿和老年疾病的例子载脂蛋白e.pdfVIP

Selection on Alleles Affecting Human Longevity and Late-Life Disease: The Example of Apolipoprotein E ¤ Fotios Drenos* , Thomas B. L. Kirkwood Institute for Ageing and Health, Newcastle University, Newcastle Upon Tyne, Tyne, United Kingdom 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 e2 and e3 alleles of the gene at the expense of the e4 allele was predicted from the model. The e2 allele frequency was found to increase slightly more rapidly than that for e3, 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. Citation: Drenos F, Kirkwood TBL (2010) Selection on Alleles Affecting Human Longevity and Late-Life Disease: The Example of Apolipoprotein E. PLoS ONE 5(4): e10022. doi:10.1371/journal.pone.0010022 Editor: Matt Kaeberlein, University of Washington, United States of America Received January 14, 2010; Accepted March 13, 2010; Published April 2, 2010 Copyright: 2010 Drenos, Kirkwood. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors thank the Dr Hadwen Trust for financial