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The genetic variation of our species reflects human demographic history and adaptation to diverse local environments. Part of this genetic variation affects individual responses to exogenous substances, such as food, pollutants and drugs, and plays an important role in drug efficacy and safety. This review provides a synthesis of the evolution of loci implicated in human pharmacological response and metabolism, interpreted within the theoretical framework of population genetics and molecular evolution. In particular, I review and discuss key evolutionary aspects of different pharmacogenes in humans and other species, such as the relationship between the type of substrates and rate of evolution; the selective pressure exerted by landscape variables or dietary habits; expected and observed patterns of rare genetic variation. Finally, I discuss how this knowledge can be translated directly or after the implementation of specific studies, into practical guidelines.

Beyond drugs: the evolution of genes involved in human response to medications