A PHYLOGENOMIC STUDY OF THE MUTS FAMILY OF PROTEINS

The MutS protein of Escherichia coli plays a key role in the recogniti on and repair of errors made during the replication of DNA, Homologs o f MutS have been found in many species including eukaryotes, Archaea a nd other bacteria, and together these proteins have been grouped into the MutS family. Although many of these proteins have similar activiti es to the E.coli MutS, there is significant diversity of function amon g the MutS family members. This diversity is even seen within species; many species encode multiple MutS homologs with distinct functions. T o better characterize the MutS protein family, I have used a combinati on of phylogenetic reconstructions and analysis of complete genome seq uences. This phylogenomic analysis is used to infer the evolutionary r elationships among the MutS family members and to divide the family in to subfamilies of orthologs, Analysis of the distribution of these ort hologs in particular species and examination of the relationships with in and between subfamilies is used to identify likely evolutionary eve nts (e,g, gene duplications, lateral transfer and gene loss) in the hi story of the MutS family. In particular, evidence is presented that a gene duplication early in the evolution of life resulted in two main M utS lineages, one including proteins known to function in mismatch rep air and the other including proteins known to function in chromosome s egregation and crossing-over. The inferred evolutionary history of the MutS family is used to make predictions about some of the uncharacter ized genes and species included in the analysis. For example, since fu nction is generally conserved within subfamilies and lineages, it is p roposed that the function of uncharacterized proteins can be predicted by their position in the MutS family tree. The uses of phylogenomic a pproaches to the study of genes and genomes are discussed.