Codon expansion and systematic transcriptional deletions produce tetra-, pentacoded mitochondrial peptides

Abstract

Genes include occasionally isolated codons with a fourth (and fifth) silent nucleotide(s). Assuming tetracodons, translated hypothetical peptides align with regular GenBank proteins; predicted tetracodons coevolve with predicted tRNAs with expanded anticodons in each mammal, Drosophila and Lepidosauria mitogenomes, GC contents and with lepidosaurian body temperatures, suggesting that expanded codons are an adaptation of translation to high temperature. Hypothetically, continuous stretches of tetra- and pentacodons code for peptides. Both systematic nucleotide deletions during transcription, and translation by tRNAs with expanded anticodons could produce these peptides. Reanalyses of human nanoLc mass spectrometry peptidome data detect numerous tetra- and pentapeptides translated from the human mitogenome. These map preferentially on (BLAST-detected) human RNAs matching the human mitogenome, assuming systematic mono- and dinucleotide deletions after each third nucleotide (delRNAs). Translation by expanded anticodons is incompatible with silent nucleotides in the midst rather than at codon 3′ extremity. More than 1/3 of detected tetra- and pentapeptides assume silent positions at codon extremity, suggesting that both mechanisms, regular translation of delRNAs and translation of regular RNAs by expanded anticodons, produce this peptide subgroup. Results show that systematically deleting polymerization occurs, and confirm serial translation of expanded codons. Non-canonical transcriptions and translations considerably expand the coding potential of DNA and RNA sequences.