Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus.

@article{citeulike:2064309, abstract = {The Duffy blood group locus, which encodes a chemokine receptor, is characterized by three alleles-FY*A, FY*B, and FY*O. The frequency of the FY*O allele, which corresponds to the absence of Fy antigen on red blood cells, is at or near fixation in most sub-Saharan African populations but is very rare outside Africa. The FST value for the FY*O allele is the highest observed for any allele in humans, providing strong evidence for the action of natural selection at this locus. Homozygosity for the FY*O allele confers complete resistance to vivax malaria, suggesting that this allele has been the target of selection by Plasmodium vivax or some other infectious agent. To characterize the signature of directional selection at this locus, we surveyed DNA sequence variation, both in a 1.9-kb region centered on the FY*O mutation site and in a 1-kb region 5-6 kb away from it, in 17 Italians and in a total of 24 individuals from five sub-Saharan African populations. The level of variation across both regions is two- to threefold lower in the Africans than in the Italians. As a result, the pooled African sample shows a significant departure from the neutral expectation for the number of segregating sites, whereas the Italian sample does not. The FY*O allele occurs on two major haplotypes in three of the five African populations. This finding could be due to recombination, recurrent mutation, population structure, and/or mutation accumulation and drift. Although we are unable to distinguish among these alternative hypotheses, it is likely that the two major haplotypes originated prior to selection on the FY*O mutation.}, address = {Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.}, author = {Hamblin, M. T. and Di Rienzo, A. }, citeulike-article-id = {2064309}, issn = {0002-9297}, journal = {Am J Hum Genet}, keywords = {binding\_site, cis\_regulatory\_elements, regulatory\_evolution, regulatory\_polymorphism, regulatory\_sequence\_evolution, turnover}, month = {May}, number = {5}, pages = {1669--1679}, posted-at = {2007-12-05 22:53:19}, priority = {3}, title = {Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/10762551}, volume = {66}, year = {2000} }

TY - JOUR ID - citeulike:2064309 L3 - citeulike-article-id:2064309 TI - Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus. JF - Am J Hum Genet VL - 66 IS - 5 SP - 1669 EP - 1679 AD - Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. SN - 0002-9297 N2 - The Duffy blood group locus, which encodes a chemokine receptor, is characterized by three alleles-FY*A, FY*B, and FY*O. The frequency of the FY*O allele, which corresponds to the absence of Fy antigen on red blood cells, is at or near fixation in most sub-Saharan African populations but is very rare outside Africa. The FST value for the FY*O allele is the highest observed for any allele in humans, providing strong evidence for the action of natural selection at this locus. Homozygosity for the FY*O allele confers complete resistance to vivax malaria, suggesting that this allele has been the target of selection by Plasmodium vivax or some other infectious agent. To characterize the signature of directional selection at this locus, we surveyed DNA sequence variation, both in a 1.9-kb region centered on the FY*O mutation site and in a 1-kb region 5-6 kb away from it, in 17 Italians and in a total of 24 individuals from five sub-Saharan African populations. The level of variation across both regions is two- to threefold lower in the Africans than in the Italians. As a result, the pooled African sample shows a significant departure from the neutral expectation for the number of segregating sites, whereas the Italian sample does not. The FY*O allele occurs on two major haplotypes in three of the five African populations. This finding could be due to recombination, recurrent mutation, population structure, and/or mutation accumulation and drift. Although we are unable to distinguish among these alternative hypotheses, it is likely that the two major haplotypes originated prior to selection on the FY*O mutation. KW - binding_site KW - cis_regulatory_elements KW - regulatory_evolution KW - regulatory_polymorphism KW - regulatory_sequence_evolution KW - turnover AU - Hamblin, MT AU - Di Rienzo, A PY - 2000/05// UR - http://view.ncbi.nlm.nih.gov/pubmed/10762551 ER -