Elucidating the origins and functions of unknown genes

描述(由申请人提供)：细菌基因组中的大多数基因，即使在有广泛实验证据的物种中，也具有假设或未知的功能。这一提议的目的是通过阐明“ORFans”的来源和功能来研究这类神秘的基因，即基因组中编码与任何其他基因组中的蛋白质没有同源性(而且往往没有结构相似性)的蛋白质的序列。此外，ORFan基因的独特性禁止使用任何传统上被用来建立基因功能的基于同源性的方法。因此，这些基因对发现它们在细菌基因组中的作用提出了重大挑战。在许多方面，这些基因构成了细菌基因组中最耐人寻味的部分，因为它们为新基因的起源提供了线索，并可能对细菌的显著多样性和适应性做出贡献。虽然已经假设ORFans可能代表非编码区而不是实际的基因，但我们最近证实，存在于大肠杆菌基因组中的绝大多数ORFans处于选择性限制之下，并编码功能蛋白。通过结合实验和生物信息学方法，本提案将分析ORFan的起源、功能和结构特性，以及它们如何在细胞功能中发挥关键作用。

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.