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Chapter 5 : Reprint of Temin's 1971 Paper Proposing the Protovirus Hypothesis
Following the discovery of reverse transcriptase and widespread acceptance of the provirus hypothesis, Howard Temin turned his attention to the possible roles of RNA-directed DNA synthesis (reverse transcription) in the cells of healthy organisms. He predicted that this unique mode of information transfer was not restricted to viruses but would also be found in healthy cells, where the transfer of information from RNA to DNA might play a role both in normal development and in generating the mutations responsible for non-virus-induced carcinogenesis. These considerations formed the basis of the protovirus hypothesis, as discussed in this 1971 editorial. The central predictions of the protovirus hypothesis, the existence of reverse transcriptase and RNA->DNA information transfer in cells as well as in viruses, have been thoroughly substantiated. Reverse transcriptases not only are widely distributed in eukaryotes (including yeasts, plants, and animals) but also have been found in bacteria. In mammals, transposable elements that move via RNA->DNA information transfer (retrotransposons) constitute approximately 10% of genomic DNA. Also as predicted in the protovirus hypothesis, mutations induced by the movement of retrotransposons can contribute to the development of cancer both by activating oncogenes and by inactivating tumor suppressor genes. The retrotransposons that have been described to date appear to be parasitic self-replicating elements that transpose to random sites throughout the genome. However, much remains to be learned concerning the molecular mechanisms of development and differentiation, and a normal physiological role for RNA->DNA information transfer may still await discovery.