SARS-CoV-2 evasion from ADAR hyper-editing is both genome-encoded and sustained by the virus replication strategy

SARS-CoV-2 is threatening the human society because of its capability to subvert antiviral defenses, causing cytokine hyper-activation and prolonged damage in multiple tissues with unpredictable outcomes in the mid-long term. Here, we evaluated the role of ADAR, an interferon-stimulated gene able to control the activation of the immune system and to directly modify exogenous dsRNAs, during in-vivo infection by SARS-CoV-2. After accurate analysis of 863 RNA-seq samples from different species, we identified ADAR-mediated hyper-editing of SARS-CoV-2 only in 49 human datasets at a low level (0.036‰ hyper edited reads on average) and preferentially on ORF6. Conversely, in mouse datasets we found abundant hyper-editing of viral reads (up to 1.16‰). The analysis of dinucleotide frequency along the ORFs of α, β, δ and γ coronaviruses highlighted the evolutionary pressure of ADAR enzymes, suggesting that the SARS-CoV-2 resistance to hyper-editing is both genome-encoded and supported by the viral transcription strategy.

Comparative Analyses of Base Compositions, DNA Sizes, and Dinucleotide Frequency Profiles in Archaeal and Bacterial Chromosomes and Plasmids

In the present paper, I compared guanine-cytosine (GC) contents, DNA sizes, and dinucleotide frequency profiles in 109 archaeal chromosomes, 59 archaeal plasmids, 1379 bacterial chromosomes, and 854 bacterial plasmids. In more than 80% of archaeal and bacterial plasmids, the GC content was lower than that of the host chromosome. Furthermore, most of the differences in GC content found between a plasmid and its host chromosome were less than 10%, and the GC content in plasmids and host chromosomes was highly correlated (Pearson’s correlation coefficient in bacteria and 0.917 in archaea). These results support the hypothesis that horizontal gene transfers have occurred frequently via plasmid distribution during evolution. GC content and chromosome size were more highly correlated in bacteria () than in archaea (). Interestingly, there was a tendency for archaea with plasmids to have higher GC content in the chromosome and plasmid than those without plasmids. Thus, the dinucleotide frequency profile of the archaeal plasmids has a bias toward high GC content.

Using Growing Self-Organising Maps to Improve the Binning Process in Environmental Whole-Genome Shotgun Sequencing

Metagenomic projects using whole-genome shotgun (WGS) sequencing produces many unassembled DNA sequences and small contigs. The step of clustering these sequences, based on biological and molecular features, is called binning. A reported strategy for binning that combines oligonucleotide frequency and self-organising maps (SOM) shows high potential. We improve this strategy by identifying suitable training features, implementing a better clustering algorithm, and defining quantitative measures for assessing results. We investigated the suitability of each of di-, tri-, tetra-, and pentanucleotide frequencies. The results show that dinucleotide frequency is not a sufficiently strong signature for binning 10 kb long DNA sequences, compared to the other three. Furthermore, we observed that increased order of oligonucleotide frequency may deteriorate the assignment result in some cases, which indicates the possible existence of optimal species-specific oligonucleotide frequency. We replaced SOM with growing self-organising map (GSOM) where comparable results are obtained while gaining7%–15%speed improvement.