Getting Started in Gene Orthology and Functional Analysis

selection pressure on a gene, revealed from its evolutionary history, is determined by the role played by the gene, i.e., its biological function. The known conservation of a gene's sequence coupled with the knowledge of the timing/dating of evolutionary events provides clues about the gene's function. If a gene is preserved in all species with high sequence similarity and there are only a few duplication events along its evolutionary history, we have high confidence that its orthologs have the same function in different species. On the other hand, a large number of duplications and/or deletions along a gene's evolutionary history could indicate neofunctionalization and/or nonorthologous gene displacement (3), and consequently, orthologs in different genomes may have different functions. These facts highlight the significance of function- oriented ortholog identification. In this article, we will review the general procedures to identify orthologs and make ortholog groups. We will focus on the functional analyses of orthologs, review previous work to assess functional consistency of orthologs, and make suggestions to construct better ortholog groups. Lastly, because orthologs can only be identified when the whole gene inventories from all the involved species are examined, the distribution of identified orthologs among species is an immediate result of looking into the composition of ortholog groups. Compo- sition of ortholog groups, which bears important information for downstream re- search and applications, will also be briefly discussed.