High genomic deleterious mutation rates in hominids

被引:288
作者
Eyre-Walker, A [1 ]
Keightley, PD
机构
[1] Univ Sussex, Ctr Study Evolut, Brighton BN1 9QG, E Sussex, England
[2] Univ Sussex, Sch Biol Sci, Brighton BN1 9QG, E Sussex, England
[3] Univ Edinburgh, Inst Cell Anim & Populat Biol, Edinburgh EH9 3JT, Midlothian, Scotland
关键词
D O I
10.1038/16915
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
It has been suggested that humans may suffer a high genomic deleterious mutation rate(1,2). Here we test this hypothesis by applying a variant of a molecular approach(3) to estimate the deleterious mutation rate in hominids from the level of selective constraint in DNA sequences. Under conservative assumptions, we estimate that an average of 4.2 amino-acid-altering mutations per diploid per generation have occurred in the human lineage since humans separated from chimpanzees. Of these mutations, we estimate that at least 38% have been eliminated by natural selection, indicating that there have been more than 1.6 new deleterious mutations per diploid genome per generation. Thus, the deleterious mutation rate specific to protein-coding sequences alone is close to the upper limit tolerable by a species such as humans that has a low reproductive rate(4), indicating that the effects of deleterious mutations may have combined synergistically, Furthermore, the level of selective constraint in hominid protein-coding sequences is atypically low, A large number of slightly deleterious mutations may therefore have become fixed in hominid lineages.
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页码:344 / 347
页数:4
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