MBE Advance Access published online on February 12, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msh074
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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1 Centre de recherche, Hôpital Sainte-Justine, Université de Montréal, Québec, H3T 1C5, Canada
* To whom correspondence should be addressed. E-mail: damian.labuda{at}umontreal.ca.
The human scavenger receptor class B type I (SR-BI and splice variant SR-BII) plays a central role in HDL cholesterol metabolism and represents a candidate gene for a number of related diseases. We examined the genetic diversity of its coding and flanking regions in a sample of 178 chromosomes from individuals of European, African, East Asian (including South-East Asian), Middle-Eastern as well as Amerindian descent. Nine of the 14 polymorphisms observed are new. Four of the 5 variants causing amino acid replacements, G2S, S229G, R484W and G499R, are likely to affect protein structure and function. SR-BI/BII diversity is partitioned among 19 haplotypes; all but one interconnected by single mutation or a recombination event. Such tight haplotype network and the unusual geographic partitioning of this diversity, high not only in Africa but in East-Asia as well, suggests its recent origin and possible effect of selection. Coalescent analysis infers a relatively short time to the most recent common ancestor and points to population expansion in Africa and East Asia. These two continents differ significantly in pairwise FST values, differing as well from a single cluster formed by Europe, Middle East and America. In the context of findings for similarly analyzed other loci, we propose that a selective sweep at the origin of modern human populations could explain the low level of ancestral SR-BI/II diversity. The unusually deep split between Africa and Asia, well beyond the Upper Paleolithic when inferred under neutrality, is consistent with subsequent geographical and demographic expansion favoring the accumulation of new variants, especially in groups characterized by large effective population sizes, such as Asians and Africans. The relevance of such partitioning of SR-BI/II diversity remains to be investigated in genetic epidemiological studies which can be guided by the present findings. Key Words:
human populations, genetic diversity, scavenger receptor gene, coalescence analysis
© 2004 Society for Molecular Biology and Evolution
Original Articles
Genetic Diversity Patterns in the SR-BI/II Locus Can Be Explained by a Recent Selective Sweep
2 Centre de recherche, Hôpital Sainte-Justine, Université de Montréal, Québec, H3T 1C5, Canada; Département de Pédiatrie, Université de Montréal, Québec, H3T 1C5, Canada
3 Centre de recherche, Hôpital Sainte-Justine, Université de Montréal, Québec, H3T 1C5, Canada; Département de Nutrition, Université de Montréal, Québec, H3T 1C5, Canada
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