Using Phylogeny and a Conserved Genomic Neighborhood Analysis to Extract and Visualize Gene Sets Involved in Target Gene Function: The Case of [NiFe]-hydrogenase and Succinate Dehydrogenase.

Several enzymes have subunits that require the addition of cofactors or maturation of the active center, which is facilitated by other genes. Information on these functionally-related genes not only aids in the functional anal-ysis of target genes, but is also useful for heterologous expression. In the present study, we analyzed the homologs of a target gene and their relationships with adjacent genes within the genome by constructing clusters of neighboring genes, quantifying the number of clustered genes, and examining their conservation in a taxonomic clade of target gene homologs. [NiFe]-hydrogenase was selected as the target because of the availability of a concrete database for subsequent evaluations in our anal-ysis. The present results indicate that genes associated with target gene function were conserved according to the molecular phylogeny of the target gene. We subsequently introduced automated clustering of the phylogenetic tree clade of clustered genes and applied this method to large datasets not yet analyzed and our previous data. The results obtained suggest that this approach provides insights into a comprehensive set of genes involved in cellular functions, particularly when the genes being analyzed are complex and require maturation. The procedure developed herein also provided similar and reproducible results on previously analyzed succinate dehydrogenase, which was not arbitrary.