title: Positive selection of protective variants for type 2 diabetes from the Neolithic onward: a case study in Central Asia.
abstract: 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.
authors: 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.
authors: Laure
authors: L
authors: Ségurel
authors: Frederic
authors: F
authors: Austerlitz
authors: Bruno
authors: B
authors: Toupance
authors: Mathieu
authors: M
authors: Gautier
authors: Joanna L
authors: JL
authors: Kelley
authors: Patrick
authors: P
authors: Pasquet
authors: Christine
authors: C
authors: Lonjou
authors: Myriam
authors: M
authors: Georges
authors: Sarah
authors: S
authors: Voisin
authors: Corinne
authors: C
authors: Cruaud
authors: Arnaud
authors: A
authors: Couloux
authors: Tatyana
authors: T
authors: Hegay
authors: Almaz
authors: A
authors: Aldashev
authors: Renaud
authors: R
authors: Vitalis
authors: Evelyne
authors: E
authors: Heyer
mesh_terms: D000483:Alleles; D001209:Asia, Central; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012424:Rural Population; D012641:Selection, Genetic