Elucidating the origins and functions of unknown genes

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): The majority of genes in bacterial genomes, even in species for which extensive experimental evidence is available, are of hypothetical or unknown functions. The aims of this proposal are to investigate this enigmatic class of genes by elucidating the source and functions of "ORFans", i.e., sequences within a genome that encode proteins having no homology (and often no structural similarity) to proteins in any other genome. Moreover, the uniqueness of ORFan genes prohibits use of any of homology-based methods that have traditionally been employed to establish gene function. Thus, these genes present a major challenge to discovering their roles in bacterial genomes. In many respects, these genes constitute the most intriguing portion of bacterial genomes because they give clue to how new genes originate, and likely contribute to the remarkable diversification and adaptation of bacteria. Although it has been hypothesized that ORFans might represent non-coding regions rather than actual genes, we have recently established that the vast majority that ORFans present in the E. coli genome are under selective constraints and encode functional proteins. By combining experimental and bioinformatic approaches, the present proposal will analyze the origins, functions and structural properties of ORFans, and how they have assumed key roles in cellular function.