Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.

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,...

Full description

Saved in:
Bibliographic Details
Main Authors: Fotios Drenos, Thomas B L Kirkwood
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-04-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010022&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850133833414868992
author Fotios Drenos
Thomas B L Kirkwood
author_facet Fotios Drenos
Thomas B L Kirkwood
author_sort Fotios Drenos
collection DOAJ
description 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.
format Article
id doaj-art-4bb0d544ee3248c3a6e931306e3f89d3
institution OA Journals
issn 1932-6203
language English
publishDate 2010-04-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-4bb0d544ee3248c3a6e931306e3f89d32025-08-20T02:31:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-04-0154e1002210.1371/journal.pone.0010022Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.Fotios DrenosThomas B L KirkwoodIt 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010022&type=printable
spellingShingle Fotios Drenos
Thomas B L Kirkwood
Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.
PLoS ONE
title Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.
title_full Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.
title_fullStr Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.
title_full_unstemmed Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.
title_short Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.
title_sort selection on alleles affecting human longevity and late life disease the example of apolipoprotein e
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010022&type=printable
work_keys_str_mv AT fotiosdrenos selectiononallelesaffectinghumanlongevityandlatelifediseasetheexampleofapolipoproteine
AT thomasblkirkwood selectiononallelesaffectinghumanlongevityandlatelifediseasetheexampleofapolipoproteine