A census of protein repeats.

In this study, we analyzed all known protein sequences for repeating amino acid segments. Although duplicated sequence segments occur in 14 % of all proteins, eukaryotic proteins are three times more likely to have internal repeats than prokaryotic proteins. After clustering the repetitive sequence segments into families, we find repeats from eukaryotic proteins have little similarity with prokaryotic repeats, suggesting most repeats arose after the prokaryotic and eukaryotic lineages diverged. Consequently, protein classes with the highest incidence of repetitive sequences perform functions unique to eukaryotes. The frequency distribution of the repeating units shows only weak length dependence, implicating recombination rather than duplex melting or DNA hairpin formation as the limiting mechanism underlying repeat formation. The mechanism favors additional repeats once an initial duplication has been incorporated. Finally, we show that repetitive sequences are favored that contain small and relatively water-soluble residues. We propose that error-prone repeat expansion allows repetitive proteins to evolve more quickly than non-repeat-containing proteins.