Functional Classification of Inositol-5-Monophosphate Dehydrogenase (IMPDH) Brian Chen, University of Pittsburgh Hugh B. Nicholas, Ph.D., Pittsburgh Supercomputing Center June 13 th , 2008 Introduction The sequence of a gene or protein holds a lot of information about its biochemical function and physiological role. Sequences or parts of sequences are often conserved in genes or proteins throughout evolution so that many different organisms will share a similar gene. These homologues are grouped together and referred to as gene or protein superfamilies; but changes could alter sequences in such a way that functions can change or be eliminated. Orthologous sequences are characterized as having minor mutations with the original role still conserved. On the other hand, mutations can be associated with the process of gene duplication to result in a new function, generating what is known as paralogous sequences. (Nicholas, Ropelewski, and Deerfield 572) By analyzing the conserved segments of sequences and pinpointing the differences, residues crucial to the role changes can be identified. With more understanding of residues that contribute to change, the functions of proteins encoded by newly discovered genes can be predicted. (Nicholas, Deerfield, and Ropelewski 1174) Functional classification or determining what role a protein plays can be accomplished using phylogenomic inference, which assumes evolutionary influence. Traditionally, database searching was used to characterize a newly discovered gene by comparing it to known, sequenced genes. However, phylogenomic inference is more advantageous because it is less error-prone than database searching and can also identify existing annotation errors. From the construction of a phylogenetic tree, relations of a protein’s function can be seen amongst species.