Comparative study of synonymous codon usage variations between the nucleocapsid and spike genes of coronavirus, and C-type lectin domain genes of human and mouse

Abstract

Coronaviruses (CoVs) are single-stranded RNA viruses which contain the largest RNA genomes, and severe acute respiratory syndrome coronavirus (SARS-CoV), a newly found group 2 CoV, emerged as infectious disease with high mortality rate. In this study, we compared the synonymous codon usage patterns between the nucleocapsid and spike genes of CoVs, and C-type lectin domain (CTLD) genes of human and mouse on the codon basis. Findings indicate that the nucleocapsid genes of CoVs were affected from the synonymous codon usage bias than spike genes, and the CTLDs of human and mouse partially overlapped with the nucleocapsid genes of CoVs. In addition, we observed that CTLDs which showed the similar relative synonymous codon usage (RSCU) patterns with CoVs were commonly derived from the human chromosome 12, and mouse chromosome 6 and 12, suggesting that there might be a specific genomic region or chromosomes which show a more similar synonymous codon usage pattern with viral genes. Our findings contribute to developing the codon-optimization method in DNA vaccines, and further study is needed to determine a specific correlation between the codon usage patterns and the chromosomal locations in higher organisms.

Figure 1

Principal component analysis of the % GC contents on the 1^st, 2^nd and 3^rd codon position. The first two factors from the principal component analysis (PRIN1 and PRIN2) were presented with each eigenvalue proportion. Nucleocapsid (A) and spike (B) coding genes of Coronavirus genus were compared with CTLD genes of human (homo sapiens) and mouse (mus musculus) species (C, D). Family names of CTLDs were also presented with each plot. G1, Group 1 CoV; G2, Group 2 CoV; G3, Group 3 CoV; N, nucleocapsid gene of CoV; S, spike gene of CoV; homo, homo sapiens; mus, mus musculus.

Figure 2

The results of phylogenetic analysis using the CTLD genes of human (homo sapiens) and mouse (mus musculus) species (A), and the scatter plots of the correspondence analysis using the relative synonymous codon usage values of the nucleocapsid and spike genes of CoVs as well as the CTLDs of human and mouse (B). Phylogram was derived by Neighbor-Joining method with bootstrap analysis of 1000 iterations, and bootstrap values (%) that are not 100% are represented as circulated numbers in each node. Each chromosome source of CTLD was also presented on the right column of tree. G1, Group 1 CoV; G2, Group 2 CoV; G3, Group 3 CoV; N, nucleocapsid gene of CoV; S, spike gene of CoV; CLEC, C-type lectin domain gene.

Figure 3

The profiles of the relative synonymous codon usage were shown as the vertical bar graph. The nucleocapaid (A) and spike (B) genes of human and mouse SARS-CoVs, as well as the human and mouse CTLD genes which were located near the nucleocapsid genes of SARS-CoVs (C) and were located far from those of SARS-CoVs (D) in the correspondence analysis in Figure 2B are presented. Genbank accession numbers are presented in legends. G1, Group 1 CoV; G2, Group 2 CoV; G3, Group 3 CoV; N, nucleocapsid gene of CoV; S, spike gene of CoV; CLEC, C-type lectin domain gene.