title: Evolutionary origin, diversification and specialization of eukaryotic MutS homolog mismatch repair proteins.
abstract: Most eubacteria, and all eukaryotes examined thus far, encode homologs of the DNA mismatch repair protein MutS. Although eubacteria encode only one or two MutS-like proteins, eukaryotes encode at least six distinct MutS homolog (MSH) proteins, corresponding to conserved (orthologous) gene families. This suggests evolution of individual gene family lines of descent by several duplication/specialization events. Using quantitative phylogenetic analyses (RASA, or relative apparent synapomorphy analysis), we demonstrate that comparison of complete MutS protein sequences, rather than highly conserved C-terminal domains only, maximizes information about evolutionary relationships. We identify a novel, highly conserved middle domain, as well as clearly delineate an N-terminal domain, previously implicated in mismatch recognition, that shows family-specific patterns of aromatic and charged amino acids. Our final analysis, in contrast to previous analyses of MutS-like sequences, yields a stable phylogenetic tree consistent with the known biochemical functions of MutS/MSH proteins, that now assigns all known eukaryotic MSH proteins to a monophyletic group, whose branches correspond to the respective specialized gene families. The rooted phylogenetic tree suggests their derivation from a mitochondrial MSH1-like protein, itself the descendent of the MutS of a symbiont in a primitive eukaryotic precursor.
authors.affiliation: Program in Molecular Biology, Oregan State University, Corvallis, OR 97331, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Culligan
authors.forename: G
authors.initials: G
authors.lastname: Meyer-Gauen
authors.forename: J
authors.initials: J
authors.lastname: Lyons-Weiler
authors.forename: J B
authors.initials: JB
authors.lastname: Hays
mesh_terms: D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D020137:Base Pair Mismatch; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D000251:Adenosine Triphosphatases; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli