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Genome Biol Evol. 2015 Aug 28;7(9):2569-84. doi: 10.1093/gbe/evv166.

Natural Selection at the Brush-Border: Adaptations to Carbohydrate Diets in Humans and Other Mammals.

Author information

1
Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy.
2
Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy Dino Ferrari Centre, Department of Physiopathology and Transplantation, University of Milan, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Italy.
3
Department of Physiopathology and Transplantation, University of Milan, Italy Don C. Gnocchi Foundation ONLUS, IRCCS, Milan, Italy.
4
Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy manuela.sironi@bp.lnf.it.

Abstract

Dietary shifts can drive molecular evolution in mammals and a major transition in human history, the agricultural revolution, favored carbohydrate consumption. We investigated the evolutionary history of nine genes encoding brush-border proteins involved in carbohydrate digestion/absorption. Results indicated widespread adaptive evolution in mammals, with several branches experiencing episodic selection, particularly strong in bats. Many positively selected sites map to functional protein regions (e.g., within glucosidase catalytic crevices), with parallel evolution at SI (sucrase-isomaltase) and MGAM (maltase-glucoamylase). In human populations, five genes were targeted by positive selection acting on noncoding variants within regulatory elements. Analysis of ancient DNA samples indicated that most derived alleles were already present in the Paleolithic. Positively selected variants at SLC2A5 (fructose transporter) were an exception and possibly spread following the domestication of specific fruit crops. We conclude that agriculture determined no major selective event at carbohydrate metabolism genes in humans, with implications for susceptibility to metabolic disorders.

KEYWORDS:

LCT; MGAM; SI; SLC2A2; TREH; natural selection

PMID:
26319403
PMCID:
PMC4607523
DOI:
10.1093/gbe/evv166
[Indexed for MEDLINE]
Free PMC Article

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