Elevated evolutionary rate in genes with homopolymeric amino acid repeats constituting nondisordered structure.

Homopolymeric amino acid repeats are tandem repeats of single amino acids. About 650 genes are known to have repeats of this kind comprising seven residues or more in the human genome. According to the evolutionary conservativeness, we classified the repeats into three categories: those whose length is conserved among mammals (CM), those whose length differs among nonprimate mammals but is conserved among primates (CP), and those whose length differs among primates (VP). The frequency of each repeat, especially Ala, Leu, Pro, and Glu repeats, varies greatly in each category. The 3D structure of homopolymeric amino acid repeats is considered to be intrinsically disordered. As expected, a large proportion of the repeats had a disordered structure, and nearly half of the repeats were predicted as completely disordered. However, a number of the repeats predicted to have nondisordered structure: 13% and 25% of the repeats for categories CM and VP, respectively. Comparison of the substitution rates showed a higher Ka/Ks ratio for the genes with not disordered repeats than the genes with disordered repeats. These results indicate that amino acid substitution rates have been elevated in the genes with nondisordered repeats.