Abstract
Proteomic MS/MS mass spectrometry detections are usually biased towards peptides cleaved by experimentally added digestion enzyme(s). Hence peptides resulting from spontaneous degradation and natural proteolysis usually remain undetected. Previous analyses of tryptic human proteome data (cleavage after K, R) detected non-canonical tryptic peptides translated according to tetra- and pentacodons (codons expanded by silent mono- and dinucleotides), and from transcripts systematically (a) deleting mono-, dinucleotides after trinucleotides (delRNAs), (b) exchanging nucleotides according to 23 bijective transformations. Nine symmetric and fourteen asymmetric nucleotide exchanges (X↔Y, e.g. A↔C; and X→Y→Z→X, e.g. A→C→G→A) produce swinger RNAs. Here unbiased reanalyses of these proteomic data detect preferentially non-canonical tryptic peptides despite assuming random cleavage. Unbiased analyses couldn't reconstruct experimental tryptic digestion if most detected non-canonical peptides were false positives. Detected non-tryptic non-canonical peptides map preferentially on corresponding, previously described non-canonical transcripts, as for tryptic non-canonical peptides. Hence unbiased analyses independently confirm previous trypsin-biased analyses that showed translations of del- and swinger RNA and expanded codons. Accounting for natural proteolysis completes trypsin-biased mitopeptidome analyses, independently confirms non-canonical transcriptions and translations.
Highlights
Protein sequences are more complex than texts written in natural human languages [1]
Proteomic analyses of the 96 human proteome extracts [112], when no specific cleavage enzyme is specified, lasted about 10 days for each unsupervised analysis. Four such unbiased 10-day long searches were performed, for peptides matching translations of the nine deltransformations of the human mitogenome, and of the 23 swinger-transformed versions of the human mitogenome
The latter are translated according to three codon sizes: regular tricodons, tetra- and pentacodons, which are regular codons expanded by silent mono- and dinucleotides
Summary
Protein sequences are more complex than texts written in natural human languages [1] This implies that genes include superimposed information, overprinted on the classical protein coding gene; for example, the three frames of the shortest self-replicating circular RNA virusoid code for proteins [2]. X possesses peculiar mathematical properties that enable retrieval of translational frame [3,4,5,6,7,8,9,10]. This punctuation code can be considered as cryptic superimposed information
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