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  • Title: Two genetic codes, one genome: frameshifted primate mitochondrial genes code for additional proteins in presence of antisense antitermination tRNAs.
    Author: Seligmann H.
    Journal: Biosystems; 2011 Sep; 105(3):271-85. PubMed ID: 21669250.
    Abstract:
    Genomic amino acid usages coevolve with cloverleaf formation capacities of corresponding primate mitochondrial tRNAs, also for antisense tRNAs, suggesting translational function for sense and antisense tRNAs. Some antisense tRNAs are antitermination tRNAs (anticodons match stops (UAR: UAA, UAG; AGR: AGA, AGG)). Genomes possessing antitermination tRNAs avoid corresponding stops in frames 0 and +1, preventing translational antitermination. In frame +2, AGR stop frequencies and corresponding antisense antitermination tRNAs coevolve positively. This suggests expression of frameshifted overlapping genes, potentially shortening genomes, increasing metabolic efficiency. Blast analyses of hypothetical proteins translated from one and seven +1, respectively, +2 frameshifted human mitochondrial protein coding genes align with eleven GenBank sequences (31% of the mitochondrial coding regions). These putative overlap genes contain few UARs, AGRs align with arginine. Overlap gene numbers increase in presence of, and with time since evolution of antitermination tRNA AGR in 57 primate mitochondrial genomes. Numbers of putative proteins translated from antisense protein coding sequences and detected by blast also coevolve positively with antitermination tRNAs; expression of two of these 'antisense' mRNAs increases under low resource availability. Although more direct evidence is still lacking for the existence of proteins translated from overlapping mitochondrial genes and for antisense tRNAs activity, coevolutions between predicted overlap genes and the antitermination tRNAs required to translate them suggest expression of overlapping genes by an overlapping genetic code. Functions of overlapping genes remain unknown, perhaps originating from dual lifestyles of ancestral free living-parasitic mitochondria. Their amino acid composition suggests expression under anaerobic conditions.
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