RNA editing as a source of genetic variation.

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Kinetoplastid RNA editing alters mitochondrial RNA transcripts by addition and deletion of uridine residues, producing open reading frames that may be twice as long as the original RNA. Although the COIII gene encoding cytochrome c oxidase subunit III in Trypanosoma brucei is edited along its entire length, the presumably homologous genes in two related trypanosomes, Leishmania tarentolae and Crithidia fasciculata, are only modestly edited at their 5' ends. We used a comparative approach to investigate the evolution of an edited gene and to determine how well editing creates conserved protein sequences. As RNA editing probably involves the pairing of several guide RNA molecules with the messenger RNA, we expected the edited proteins to be resistant to evolutionary change. Here we report that RNA editing is extensive in the mitochondria of four species of the insect parasite Herpetomonas, which is possibly an evolutionary precursor of T. brucei and L. tarentolae, and the discovery that RNA editing is a novel source of frameshift mutations over evolutionary time. The edited proteins accumulate mutations nearly twice as rapidly as the unedited versions.