Michel, C. J. | bioRxiv Science

bioRxiv2020

Characterization of accessory genes in coronavirus genomes

The Covid19 infection is caused by the SARS-CoV-2 virus, a novel member of the coronavirus (CoV) family. CoV genomes code for a ORF1a / ORF1ab polyprotein and four structural proteins widely studied as major drug targets. The genomes also contain a variable number of open reading frames (ORFs) coding for accessory proteins that are not essential for virus replication, but appear to have a role in pathogenesis. The accessory proteins have been less well characterized and are difficult to predict by classical bioinformatics methods. We propose a computational tool GOFIX to characterize potential ORFs in virus genomes. In particular, ORF coding potential is estimated by searching for enrichment in motifs of the X circular code, that is known to be over-represented in the reading frames of viral genes. We applied GOFIX to study the SARS-CoV-2 and related genomes including SARS-CoV and SARS-like viruses from bat, civet and pangolin hosts, focusing on the accessory proteins. Our analysis provides evidence supporting the presence of overlapping ORFs 7b, 9b and 9c in all the genomes and thus helps to resolve some differences in current genome annotations. In contrast, we predict that ORF3b is not functional in all genomes. Novel putative ORFs were also predicted, including a truncated form of the ORF10 previously identified in SARS-CoV-2 and a little known ORF overlapping the Spike protein in Civet-CoV and SARS-CoV. Our findings contribute to characterizing sequence properties of accessory genes of SARS coronaviruses, and especially the newly acquired genes making use of overlapping reading frames.

bioinformatics↗

bioRxiv2020

Potential role of the X circular code in the regulation of gene expression

The X circular code is a set of 20 trinucleotides (codons) that has been identified in the protein-coding genes of most organisms (bacteria, archaea, eukaryotes, plasmids, viruses). It has been shown previously that the X circular code has the important mathematical property of being an error-correcting code. Thus, motifs of the X circular code, i.e. a series of codons belonging to X, which are significantly enriched in the genes, allow identification and maintenance of the reading frame in genes. X motifs have also been identified in many transfer RNA (tRNA) genes and in important functional regions of the ribosomal RNA (rRNA), notably in the peptidyl transferase center and the decoding center. Here, we investigate the potential role of X motifs as functional elements in the regulation of gene expression. Surprisingly, the definition of a simple parameter identifies several relations between the X circular code and gene expression. First, we identify a correlation between the 20 codons of the X circular code and the optimal codons/dicodons that have been shown to influence translation efficiency. Using previously published experimental data, we then demonstrate that the presence of X motifs in genes can be used to predict the level of gene expression. Based on these observations, we propose the hypothesis that the X motifs represent a new genetic signal, contributing to the maintenance of the correct reading frame and the optimization and regulation of gene expression. Author SummaryThe standard genetic code is used by (quasi-) all organisms to translate information in genes into proteins. Recently, other codes have been identified in genomes that increase the versatility of gene decoding. Here, we focus on the circular codes, an important class of genome codes, that have the ability to detect and maintain the reading frame during translation. Motifs of the X circular code are enriched in protein-coding genes from most organisms from bacteria to eukaryotes, as well as in important molecules in the gene translation machinery, including transfer RNA (tRNA) and ribosomal RNA (rRNA). Based on these observations, it has been proposed that the X circular code represents an ancestor of the standard genetic code, that was used in primordial systems to simultaneously decode a smaller set of amino acids and synchronize the reading frame. Using previously published experimental data, we highlight several links between the presence of X motifs in genes and more efficient gene expression, supporting the hypothesis that the X circular code still contributes to the complex dynamics of gene regulation in extant genomes.

bioinformatics↗