Intellectual Merit: Reverse transcriptases are enzymes that perform DNA synthesis on RNA templates. It is widely believed that reverse transcriptase activity is mostly used by selfish genetic elements, such as retrotransposons and retroviruses, for their own replication and propagation. The only known exceptions are telomerases, which are encoded by single-copy genes and maintain eukaryotic chromosome ends by repeatedly copying a small region of the associated RNA template onto DNA. This project seeks to understand the evolutionary origins and cellular functions of RNA-dependent polymerization by studying novel reverse transcriptase-related genes found in diverse eukaryotes, using computational, biochemical, and genetic approaches. Phylogenetic distribution and relationships with other classes of reverse transcriptases, enzymatic activity of the encoded products, and possible involvement in cellular pathways will be investigated. These studies could reveal previously unknown roles for RNA-dependent polymerization in living cells. Elucidation of evolutionary origins and cellular functions of reverse transcriptase-related genes is of fundamental importance and may be expected to have a major impact on the fields of molecular biology, genetics, and evolution.
Broader Impacts: The project will have both scientific and educational impacts. The results of the study are expected to challenge the currently established views on the role of RNA-dependent polymerization, which may be significantly under-appreciated. Educational activities will include training of graduate and undergraduate students and their direct involvement in research, which will result in student-coauthored publications. Other activities will include: active participation in national and international scientific meetings to ensure broader dissemination of the results to members of the scientific community; organization of regional meetings to provide venues for information exchange and training and, through travel grants, to attract minority participants; and active involvement in science fairs at local high schools. Outreach efforts will be aimed at bringing results of NSF-funded research to non-specialists and the general public through media interviews and contributions to popular books targeted at wider audiences.