Adaptation to food resources is a driver of molecular evolution in mammals and a major transition in human history, the development of agriculture, determined increased carbohydrate consumption. We investigated the evolutionary history of 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 involved positions of fundamental importance to protein function (e.g. within glucosidase catalytic crevices), with parallel evolution at SI and MGAM. In human populations five genes were targeted by positive selection. Analysis of ancient DNA samples indicated that most selected alleles were already present in the Paleolithic, thus predating the emergence of agriculture. Thus, agriculture determined no major selective event at carbohydrate metabolism genes in humans, with implications for susceptibility to metabolic disorders. Our work also provides a list of candidate functional variants to be prioritized in functional studies
