title: Natural Selection at the Brush-Border: Adaptations to Carbohydrate Diets in Humans and Other Mammals.
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.
authors: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy.
authors: Chiara
authors: C
authors: Pontremoli
authors: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy.
authors: Alessandra
authors: A
authors: Mozzi
authors: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy.
authors: Diego
authors: D
authors: Forni
authors: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy.
authors: Rachele
authors: R
authors: Cagliani
authors: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy.
authors: Uberto
authors: U
authors: Pozzoli
authors: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy.
authors: Giorgia
authors: G
authors: Menozzi
authors: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy.
authors: Jacopo
authors: J
authors: Vertemara
authors: 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.
authors: Nereo
authors: N
authors: Bresolin
authors: Department of Physiopathology and Transplantation, University of Milan, Italy Don C. Gnocchi Foundation ONLUS, IRCCS, Milan, Italy.
authors: Mario
authors: M
authors: Clerici
authors: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy manuela.sironi@bp.lnf.it.
authors: Manuela
authors: M
authors: Sironi
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics; D000483:Alleles; D000818:Animals; D050260:Carbohydrate Metabolism / Q000235:genetics; D004040:Dietary Carbohydrates / Q000378:metabolism*; D019143:Evolution, Molecular; D006071:Gorilla gorilla / Q000235:genetics; D006801:Humans; D008322:Mammals / Q000235:genetics*; D008871:Microvilli / Q000201:enzymology; D002679:Pan troglodytes / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012641:Selection, Genetic; D013394:Sucrase-Isomaltase Complex / Q000235:genetics; D000520:alpha-Glucosidases / Q000235:genetics
chemical_list: D004040:Dietary Carbohydrates; D013394:Sucrase-Isomaltase Complex; D000520:alpha-Glucosidases
keywords: LCT; MGAM; SI; SLC2A2; TREH; natural selection