Comparative Analysis of Human Coronaviruses Focusing on Nucleotide Variability and Synonymous Codon Usage Pattern

Abstract

AbstractPrevailing pandemic across the world due to SARSCoV-2 drawing great attention towards discovering its evolutionary origin. We perform an exploratory study to understand the variability of the whole coding region of possible proximal evolutionary neighbours of SARSCoV-2. We consider seven (07) human coronavirus strains from six different species as a candidate for our study.First, we observe a good variability of nucleotides across candidate strains. We did not find a significant variation of GC content across the strains for codon position first and second. However, we interestingly see huge variability of GC-content in codon position 3rd (GC3), and pairwise mean GC-content (SARSCoV, MERSCoV), and (SARSCoV-2, hCoV229E) are quite closer. While observing the relative abundance of dinucleotide feature, we find a shared typical genetic pattern, i.e., high usage of GC and CT nucleotide pair at the first two positions (P12) of codons and the last two positions (P23) of codons, respectively. We also observe a low abundance of CG pair that might help in their evolution bio-process. Secondly, Considering RSCU score, we find a substantial similarity for mild class coronaviruses, i.e., hCoVOC43, hCoVHKU1, and hCoVNL63 based on their codon hit with high RSCU value (≥ 1.5), and minim number of codons hit (count-9) is observed for MERSCoV. We see seven codons ATT, ACT, TCT, CCT, GTT, GCT and GGT with high RSCU value, which are common in all seven strains. These codons are mostly from Aliphatic and Hydroxyl amino acid group. A phylogenetic tree built using RSCU feature reveals proximity among hCoVOC43 and hCoV229E (mild). Thirdly, we perform linear regression analysis among GC content in different codon position and ENC value. We observe a strong correlation (significant p-value) between GC2 and GC3 for SARSCoV-2, hCoV229E and hCoVNL63, and between GC1 and GC3 for hCoV229E, hCoVNL63, SARSCoV. We believe that our findings will help in understanding the mechanism of human coronavirus.