Neighboring-Site Effects of Amino Acid Substitutions in the Mouse Genome

Nucleotide evolution models benefit a lot from the reported neighbor-dependent nucleotide mutations. Investigations of neighboring-site effects of amino acid substitutions may also promote the development of protein evolution models. Here, the neighboring-site effects of amino acid substitutions in the mouse genome are evaluated by grouping the 20 amino acids into four categories: nonpolar neutral (NON), polar neutral (NEU), positive (POS) and negative (NEG) amino acids. Our data indicate that amino acid substitutions are evidently neighboring-site dependent, and the most prominent bias is the NEG→NEG substitution occurring in NEG_NEG context, the frequency of which is 2-fold higher than that of expectation. The neighboring-site effects are also correlated with some types of protein secondary structures. Through this study, we conclude that like neighbor-dependent nucleotide mutations, amino acid substitutions are also neighboring-site dependent. The mutation bias of nucleotide sequence and natural or functional selection on protein structure might be two underlying reasons for the neighboring-site effects of amino acid substitutions in the mouse genome.