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Positive selection of protective variants for type 2 diabetes from the Neolithic onward: a case study in Central Asia.
MedLine Citation:
PMID:  23340510     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The high prevalence of type 2 diabetes and its uneven distribution among human populations is both a major public health concern and a puzzle in evolutionary biology. Why is this deleterious disease so common, while the associated genetic variants should be removed by natural selection? The 'thrifty genotype' hypothesis proposed that the causal genetic variants were advantageous and selected for during the majority of human evolution. It remains, however, unclear whether genetic data support this scenario. In this study, we characterized patterns of selection at 10 variants associated with type 2 diabetes, contrasting one herder and one farmer population from Central Asia. We aimed at identifying which alleles (risk or protective) are under selection, dating the timing of selective events, and investigating the effect of lifestyle on selective patterns. We did not find any evidence of selection on risk variants, as predicted by the thrifty genotype hypothesis. Instead, we identified clear signatures of selection on protective variants, in both populations, dating from the beginning of the Neolithic, which suggests that this major transition was accompanied by a selective advantage for non-thrifty variants. Combining our results with worldwide data further suggests that East Asia was particularly prone to such recent selection of protective haplotypes. As much effort has been devoted so far to searching for thrifty variants, we argue that more attention should be paid to the evolution of non-thrifty variants.European Journal of Human Genetics advance online publication, 23 January 2013; doi:10.1038/ejhg.2012.295.
Authors:
Laure Ségurel; Frederic Austerlitz; Bruno Toupance; Mathieu Gautier; Joanna L Kelley; Patrick Pasquet; Christine Lonjou; Myriam Georges; Sarah Voisin; Corinne Cruaud; Arnaud Couloux; Tatyana Hegay; Almaz Aldashev; Renaud Vitalis; Evelyne Heyer
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  -     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Eco-Anthropologie et Ethnobiologie, UMR 7206, Muséum National d'Histoire Naturelle - Centre National de la Recherche Scientifique - Université Paris 7 Diderot, Paris, France [2] Department of Human Genetics, University of Chicago, Chicago, IL, USA.
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