Identification of a circular code periodicity in the bacterial ribosome: origin of codon periodicity in genes?

Abstract

Three-base periodicity (TBP), where nucleotides and higher order n-tuples are preferentially spaced by 3, 6, 9, etc. bases, is a well-known intrinsic property of protein-coding DNA sequences. However, its origins are still not fully understood. One hypothesis is that the periodicity reflects a primordial coding system that was used before the emergence of the modern standard genetic code (SGC). Recent evidence suggests that the X circular code, a set of 20 trinucleotides allowing the reading frames in genes to be retrieved locally, represents a possible ancestor of the SGC. Motifs from the X circular code have been found in the reading frame of protein-coding regions in extant organisms from bacteria to eukaryotes, in many transfer RNA (tRNA) genes and in important functional regions of the ribosomal RNA (rRNA), notably in the peptidyl transferase centre and the decoding centre. Here, we have used a powerful correlation function to search for periodicity patterns involving the 20 trinucleotides of the X circular code in a large set of bacterial proteincoding genes, as well as in the translation machinery, including rRNA and tRNA sequences. As might be expected, we found a strong circular code periodicity 0 modulo 3 in the protein-coding genes. More surprisingly, we also identified a similar circular code periodicity in a large region of the 16S rRNA. This region includes the 3ʹ major domain corresponding to the primordial proto-ribosome decoding centre and containing numerous sites that interact with the tRNA and messenger RNA (mRNA) during translation. Furthermore, 3D structural analysis shows that the periodicity region surrounds the mRNA channel that lies between the head and the body of the SSU. Our results support the hypothesis that the X circular code may constitute an ancestral translation code involved in reading frame retrieval and maintenance, traces of which persist in modern mRNA, tRNA and rRNA despite their long evolution and adaptation to the SGC.

The Relation Between k-Circularity and Circularity of Codes

“…Firstly, the circular code X (1.1) is also identified in genes of archaea, plasmids and viruses, in addition to bacteria and eukaryotes, and by two different statistical approaches (Michel 2015(Michel , 2017. Furthermore, motifs from the circular code X , called X -motifs, are significantly enriched in the genes of most organisms, from bacteria to eukaryotes (Michel et al 2017;, and also exist in the ribosomal and transfer RNAs (rRNAs and tRNAs) (Michel 2012(Michel , 2013Michel 2014, 2015;Michel and Thompson 2020). However, these X -motifs in genes are separated by words which are not in the code X .…”

“… 2019 ), and also exist in the ribosomal and transfer RNAs (rRNAs and tRNAs) (Michel 2012 , 2013 ; El Soufi and Michel 2014 , 2015 ; Dila et al. 2019 ; Michel and Thompson 2020 ). However, these X -motifs in genes are separated by words which are not in the code X .…”

A role for circular code properties in translation

“…Another indication that circular code properties may be mainly involved with translation dynamics is the recent discovery of circular code periodicities in certain regions of the 16S rRNA. These findings have been tentatively explained with the need for correct frame synchronization and retrieval in primeval forms of the translation machinery 35,39 .…”

Negative CG dinucleotide bias: An explanation based on feedback loops between Arginine codon assignments and theoretical minimal RNA rings

“…[ 66–69 ] , as noted above for tRNAs. Codon usages of the 25 self‐hybridizing RNA rings are biased for codons belonging to the natural circular code, [ 69–71 ] as noted for rRNAs, tRNAs and mRNAs.…”

“…Transfer RNAs are structurally embedded within ribosomal RNAs, [ 50,58–69 ] indicating complex multifunctional interactions between the most central biomolecules of the cell's translational apparatus. Conserved natural circular code trinucleotide motifs occur within rRNAs.…”