Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13

Abstract

The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 -4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3'-to-5' exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.

Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

“…The average percent difference in codon usage was 0.029%, or ~3 codons / 10,000, clearly showing that variation in sequences is not significantly affecting overall codon usage. This degree of mutation between strains is corroborated by a recently published study [25].…”

“…Since it is a surface protein, it is under constant pressure to avoid the immune response, and as a result, it is the least conserved of the coronavirus proteins, diverging both in its amino acid and its codon usage [25]. Being under constant selective pressure could be the reason why it has been able to adapt to the host genome more than other proteins.…”

CoV2ID: Detection and Therapeutics Oligo Database for SARS-CoV-2

“…These results demonstrate the existence of several mutated positions across the genome leading to relatively low percentage of identical sites (62 to 64%). However, the level of genetic diversity is relatively low, as shown by the high percentage of pairwise identity (>99%), suggesting that most mutations only occur in a few genomes, in line with other studies[18][19][20].…”

Patient-derived mutations impact pathogenicity of SARS-CoV-2

“…https://doi.org/10.1101/2020. 04.14.20060160 doi: medRxiv preprint in the S protein is the most variable genomic part in the betacoronavirus group (Wu et al,69 2020; Zhou et al, 2020), and some sites of S protein might be subjected to positive 70 selection (Lv et al, 2020). Despite the abundant variability of SARS-CoV-2, one key 71 question remains as to whether these mutations have any real functional impact on the 72 pathogenicity of SARS-CoV-2.…”