Population genetic and phylogenetic evidence for positive selection on regulatory mutations at the factor VII locus in humans. Export

@article{citeulike:1776701, abstract = {The abundance of cis-regulatory polymorphisms in humans suggests that many may have been important in human evolution, but evidence for their role is relatively rare. Four common polymorphisms in the 5' promoter region of factor VII (F7), a coagulation factor, have been shown to affect its transcription and protein abundance both in vitro and in vivo. Three of these polymorphisms have low-frequency alleles that decrease expression of F7 and may provide protection against myocardial infarction (heart attacks). The fourth polymorphism has a minor allele that increases the level of transcription. To look for evidence of natural selection on the cis-regulatory variants flanking F7, we genotyped three of the polymorphisms in six Old World populations for which we also have data from a group of putatively neutral SNPs. Our population genetic analysis shows evidence for selection within humans; surprisingly, the strongest evidence is due to a large increase in frequency of the high-expression variant in Singaporean Chinese. Further characterization of a Japanese population shows that at least part of the increase in frequency of the high-expression allele is found in other East Asian populations. In addition, to examine interspecific patterns of selection we sequenced the homologous 5' noncoding region in chimpanzees, bonobos, a gorilla, an orangutan, and a baboon. Analysis of these data reveals an excess of fixed differences within transcription factor binding sites along the human lineage. Our results thus further support the hypothesis that regulatory mutations have been important in human evolution.}, address = {Department of Biology, Duke University, Durham, North Carolina 27708, USA. mwhahn@ucdavis.edu}, author = {Hahn, M. W. and Rockman, M. V. and Soranzo, N. and Goldstein, D. B. and Wray, G. A.}, citeulike-article-id = {1776701}, citeulike-linkout-0 = {http://dx.doi.org/10.1534/genetics.103.025726}, citeulike-linkout-1 = {http://www.genetics.org/cgi/content/abstract/167/2/867}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15238535}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15238535}, doi = {10.1534/genetics.103.025726}, issn = {0016-6731}, journal = {Genetics}, keywords = {evolution, genetics, human, population, regulation, selection, species}, month = {June}, number = {2}, pages = {867--877}, posted-at = {2008-08-07 16:17:06}, priority = {2}, title = {Population genetic and phylogenetic evidence for positive selection on regulatory mutations at the factor VII locus in humans.}, url = {http://dx.doi.org/10.1534/genetics.103.025726}, volume = {167}, year = {2004} }

TY - JOUR ID - citeulike:1776701 L3 - citeulike-article-id:1776701 N2 - The abundance of cis-regulatory polymorphisms in humans suggests that many may have been important in human evolution, but evidence for their role is relatively rare. Four common polymorphisms in the 5' promoter region of factor VII (F7), a coagulation factor, have been shown to affect its transcription and protein abundance both in vitro and in vivo. Three of these polymorphisms have low-frequency alleles that decrease expression of F7 and may provide protection against myocardial infarction (heart attacks). The fourth polymorphism has a minor allele that increases the level of transcription. To look for evidence of natural selection on the cis-regulatory variants flanking F7, we genotyped three of the polymorphisms in six Old World populations for which we also have data from a group of putatively neutral SNPs. Our population genetic analysis shows evidence for selection within humans; surprisingly, the strongest evidence is due to a large increase in frequency of the high-expression variant in Singaporean Chinese. Further characterization of a Japanese population shows that at least part of the increase in frequency of the high-expression allele is found in other East Asian populations. In addition, to examine interspecific patterns of selection we sequenced the homologous 5' noncoding region in chimpanzees, bonobos, a gorilla, an orangutan, and a baboon. Analysis of these data reveals an excess of fixed differences within transcription factor binding sites along the human lineage. Our results thus further support the hypothesis that regulatory mutations have been important in human evolution. IS - 2 JF - Genetics SN - 0016-6731 AD - Department of Biology, Duke University, Durham, North Carolina 27708, USA. mwhahn@ucdavis.edu EP - 877 TI - Population genetic and phylogenetic evidence for positive selection on regulatory mutations at the factor VII locus in humans. VL - 167 SP - 867 KW - evolution KW - genetics KW - human KW - population KW - regulation KW - selection KW - species AU - Hahn, MW AU - Rockman, MV AU - Soranzo, N AU - Goldstein, DB AU - Wray, GA PY - 2004/06// UR - http://dx.doi.org/10.1534/genetics.103.025726 ER -