title: Overlapping genes coded in the 3'-to-5'-direction in mitochondrial genes and 3'-to-5' polymerization of non-complementary RNA by an 'invertase'.
abstract: Suppressor tRNAs induce expression of additional (off-frame) genes coded by stopless genetic codes without lengthening genomes, decreasing DNA replication costs. RNA 3'-to-5' polymerization by tRNAHis guanylyltransferase suggests further cryptic code: hypothetical 'invertases' polymerizing in the 3'-to-5' direction, advancing in the 5'-to-3' direction would produce non-complementary RNA templated by regular genes, with different coding properties. Assuming 'invertase' activity, BLAST analyses detect GenBank-stored RNA ESTs and proteins (some potentially coding for the hypothesized invertase) for human mitochondrial genes. These peptides' predicted secondary structures resemble their GenBank homologues'. 3'-to-5' EST lengths increase with their self-hybridization potential: Single-stranded RNA degradation perhaps limits 3'-to-5' elongation. Independent methods confirm predicted 3'-to-5' overlapping genes: (a) Presumed 3'-to-5' overlapping genes avoid codons belonging to circular codes; (b) Spontaneous replicational deamination (mutation) gradients occur at 3rd codon positions, unless these are involved in overlap coding, because mutations are counter selected in overlapping genes. Tests a and b converge on predicted 3'-to-5' gene expression levels. Highly expressed ones include also fewer stops, and mitochondrial genomes (in Primates and Drosophila) adapt to avoid dependence of 3'-to-5' coding upon antitermination tRNA activity. Secondary structure, circular code, gradient and coevolution analyses yield each clear positive results independently confirming each other. These positive results (including physical evidence for 3'-to-5' ESTs) indicate that 3'-to-5' coding and invertase activity is an a priori improbable working hypothesis that cannot be dismissed. Note that RNAs produced by invertases potentially produce triple-stranded DNA:RNA helices by antiparallel Hoogsteen pairings at physiological pH, as previously observed for mitochondrial genomes.
authors.affiliation: National Natural History Museum Collections, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel. podarcissicula@gmail.com
authors.forename: Hervé
authors.initials: H
authors.lastname: Seligmann
mesh_terms: D000818:Animals; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D003641:Deamination / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D019143:Evolution, Molecular; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial / Q000235:genetics*; D005807:Genes, Overlapping / Q000235:genetics*; D006801:Humans; D058977:Molecular Sequence Annotation; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames / Q000235:genetics*; D010455:Peptides / Q000737:chemistry; D058105:Polymerization; D017433:Protein Structure, Secondary; D016372:RNA, Antisense / Q000235:genetics; D018075:RNA, Complementary / Q000737:chemistry / Q000235:genetics*; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D003062:Codon; D010455:Peptides; D016372:RNA, Antisense; D018075:RNA, Complementary; D012343:RNA, Transfer; D012321:DNA-Directed RNA Polymerases