Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Atkins, John F.; Loughran, Gary; Bhatt, Pramod R.; Firth, Andrew E.; Baranov, Pavel V.

Some long-term bacterial endosymbionts of insects have their genomes reduced to the range of 160-790 kb and an A T-content >70% (243). In frameshifted cell wall genes of an endosymbiont associated with aphids, and a histidine biosynthetic gene of an endosymbiont associated with ants, frequent transcription slippage/realignment at long poly(A) runs yields 12-50% of transcripts with 'corrected' reading frames (244) . The pathogenic kinetopast protists Trypanosoma and Leishmania have long been known to have mitochondrial uridine insertion/deletion type editing. But it also occurs in the mitochondria of endosymbiont kinetoplast Perkinsela where only six protein-coding genes have been identified despite the large size of the Perkinsela mitochondrial genome. Given the number of post-editing 'problem' mRNAs (245) , potential translational 'correction' seems also likely. Ribosomal frameshifting can also compensate for the effects of otherwise inactivating singlenucleotide insertions at various places in the encoding DNA, and examples occur in the mitochondria of several free-living species. Single nucleotide inserts occur in a small number (currently 6 known) of essential genes in the mitochondria of species from 4 animal phyla and 1 protist. Compensatory +1 ribosomal frameshifting apparently yields an adequate amount of functional product (246) . An insert occurs in the NADH dehydrogenase subunit 3 gene of the majority of birds (247, 248) . The homologous gene in some turtles has the same insert and the insert likely originated in a common ancestor of birds and turtles more than 200 million years ago (246) . In some other turtles the insert is elsewhere (246, 248) . An insert also occurs in the cytochrome b genes of at least one oyster species (249) and at any of several sites in this gene in several ant species (250) . However, among the currently known instances, natural mitochondrial single-nucleotide frameshifting is most prevalent in glass sponges (251, 252) . These siliceous spicule-containing Hexactinellid sponges have exceptionally low metabolism, live in a low oxygen environment and their mitochondrial coding sequences show evidence of relaxed selection pressure (252) . The coding sequence of mitochondrial genes of several calcium carbonate spicule-containing Calcaronean sponges is largely unrecognizable and their transcripts have single or double U insertions in pre-existing short poly(U) tracts (nearly all their genes on individual and likely linear chromosomes) (253) . How the inserts occur and whether extensive compensatory ('corrective') frameshifting is involved in the synthesis of their protein products is unknown.