Selection against amino acid replacements in human proteins

Abstract

The vast majority of mutations occurring in the coding regions of human genes alter the encoded amino acids of proteins. A significant proportion of these mutations are known to disrupt the structure and/or function of human proteins. The similarity of a large fraction of amino acid residues of human protein sequences with that of other species implies that the amino acid altering mutations were purged through natural selection during the evolution of the human lineage. In contrast, due to the effects of genetic drift, amino acid replacement mutations are present within human populations at low frequencies and a high proportion of such mutations are harmful to humans. Therefore, understanding the contrasting patterns of long‐term and short‐term evolutionary histories of human proteins are vital in identifying the amino acid mutations associated with human genetic diseases.