A widespread class of reverse transcriptase-related cellular genes

This work was supported by NSF grant MCB-0821956 to I.A.

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 108 (2011):20311-20316, doi:10.1073/pnas.1100266108.

Reverse transcriptases (RTs) polymerize DNA on RNA templates. They fall into several structurallyrelated but distinct classes, and form an assemblage of RT-like enzymes which, in addition to RTs, alsoincludes certain viral RNA-dependent RNA polymerases (RdRP) polymerizing RNA on RNA templates. Itis generally believed that most RT-like enzymes originate from retrotransposons or viruses and have nospecific function in the host cell, with telomerases being the only notable exception. Here we report on thediscovery and properties of a novel class of RT-related cellular genes collectively named rvt. We presentevidence that rvt are not components of retrotransposons or viruses, but single-copy genes with acharacteristic domain structure, may contain introns in evolutionarily conserved positions, occur insyntenic regions, and evolve under purifying selection. These genes can be found in all major taxonomicgroups including protists, fungi, animals, plants, and even bacteria, although they exhibit patchyphylogenetic distribution in each kingdom. We also show that the RVT protein purified from one of itsnatural hosts, Neurospora crassa, exists in a multimeric form and has the ability to polymerize NTPs aswell as dNTPs in vitro, with a strong preference for NTPs, using Mn2+ as a cofactor. The existence of apreviously unknown class of single-copy RT-related genes calls for re-evaluation of the current views onevolution and functional roles of RNA-dependent polymerases in living cells.