title: Adaptive amino acid replacements accompanied by domain fusion in reverse transcriptase.
abstract: Two basic processes are involved in protein evolution: One is amino acid replacement and another is reorganization of structural or functional units of proteins. Multidomain or multifunctional proteins are thought to have evolved by fusion of smaller structural units such as modules or domains. Reverse transcriptase (RT) is one of such fused proteins. The N-terminal part forms of globular domain with polymerase activity and the C-terminal part forms another globular domain with ribonuclease H activity (RNase H domain). There are single-domain enzymes which are homologous with the RNase H domain. The group of enzymes is called type I ribonuclease H (RNase HI). It is most likely that the ancestors of RNase HI and the polymerase domain were fused and became contemporary RT. At fusion, amino acid replacements presumably occurred at the interface of the domains to reinforce the interdomain interactions. Such replaced amino acid residues are conserved during evolution of the fused enzyme. We analyzed the pattern of amino acid replacement at each residue site in the free form, RNase HI group, and the integrated form, RNase H domain group. Then we compared the patterns between the two forms. Drastic fitting replacements of amino acid residues occurred at four of 29 residue sites involved in interdomain contact. Hydrophilic amino acid residues of the free form were substituted with hydrophobic or ambivalent ones in the integrated form. These substitutions aid in stabilizing the fused conformation by hydrophobic interactions at the interface of the domains. These observations imply that domain fusion could have occurred with only a relatively small number of adaptive amino acid substitutions.
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shirai
authors.forename: M
authors.initials: M
authors.lastname: Go
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry*; D016914:Ribonuclease H / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: D000596:Amino Acids; D012194:RNA-Directed DNA Polymerase; D016914:Ribonuclease H; C078856:ribonuclease HI