Insights into The Codon Usage Bias of 13 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Isolates from Different Geo-locations

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of Coronavirus disease 2019 which is an infectious disease that spread throughout the world and was declared as a pandemic by the World Health Organization (WHO). In the present study, we analyzed genome-wide codon usage patterns in 13 SARS-CoV-2 isolates from different geo-locations (countries) by utilizing different CUB measurements. Nucleotide and di-nucleotide compositions displayed bias toward A/U content in all codon positions and CpU-ended codons preference, respectively. Relative Synonymous Codon Usage (RSCU) analysis revealed 8 common putative preferred codons among all the 13 isolates.Interestingly, all of the latter codons are A/U-ended (U-ended: 7, A-ended: 1). Cluster analysis (based on RSCU values) was performed and showed comparable results to the phylogenetic analysis (based on their whole genome sequences) indicating that the CUB pattern may reflect the evolutionary relationship between the tested isolates. To investigate the force (mutation and/or selection) influencing the pattern of CUB in SARS-CoV-2 coding sequences, we employed the following; (i). Effective number of codons (ENc), (ii). ENc-GC3 plot, (iii). Neutrality plot, and (iv) Codon adaptation index (CAI). According to their results, natural selection and/or other factors (not investigated in this study) may be the dominant force driving SARS-CoV-2 CUB. It is also worth mentioning that, by using the most expressed genes in human lung tissues as a reference set, some viral genes such as Nucleocapsid phosphoprotein, ORF7a protein, and surface glycoprotein had high CAI values which may indicate for selection force acting on their codon usage, as they play important roles in viral assembly and may help viruses avoid the host immune system. The outcome of our study may help in understanding the underlying factors involved in the evolution of SARS-CoV-2 viruses, and the interactions with their host. Also, it may aid in vaccine design strategies.

Characterization of Codon Usage Pattern in SARS-CoV-2

“…Thus, most codons of SARS-CoV-2 Wuhan-Hu-1 tended to be U ending. Moreover, the mean GC and AU compositions (Supplementary Figure 1B) were 37.9% and 62.1% (SARS-CoV-2 Wuhan-Hu-1), 41.0% and 59.0% (SARS-CoV Tor2), 40.8% and 59.2% (SARS-CoV Urbani), 41.5% and 58.5% (MERS-CoV HCoV-EMC), 36.8% and 63.2% (HCoV-OC43), 32.0% and 68.0% (HCoV-HKU1), 38.0% and 62.0% (HCoV-229E), 34.4% and 65.6% (HCoV-NL63), respectively indicating that SARS-CoV-2 Wuhan-Hu-1 as well as other human coronaviruses in this study were all AU rich, which was consistent with recent reports [11][12][13][14][15].…”

“…Additionally, the overall codon usage pattern of SARS-CoV-2 was generally similar to that of its phylogenetic relatives among non-human coronaviruses such as RaTG13. Our ndings are consistent with the recent observations [11][12][13][14][15] and provide new insights into the characteristics of codon usage pattern in coronaviruses. These results also have important implications for future work.…”

Natural selection plays a significant role in governing the codon usage bias in the novel SARS-CoV-2 variants of concern (VOC)

“…Similar approaches have been employed in the development of live attenuated vaccines against poliovirus ( Coleman et al, 2009 ), human respiratory syncytial virus ( Le Nouën et al, 2014 ), influenza virus ( Mueller et al, 2011 ), and dengue virus ( Shen et al, 2015 ). The present study results are similar to that of the previous studies performed on SARS-CoV-2 structural genes, validating our findings ( Dilucca et al, 2020 ; Khodary & Anwar, 2020 ; Kandeel et al, 2020 ; Gu et al, 2020 ; Tort, Castells & Cristina, 2020 ; Nyayanit et al, 2021 ).…”

“…The CAI values can be used to measure the extent of adaptability of the virus inside the host, its value ranges from 0 to 1. The higher value reveals higher gene expression and better adaptability in the host ( Khodary & Anwar, 2020 ). When comparing the CAI values of human isolated SARS-CoV-2 VOC with the closely related bat-CoVs and pangolin-CoVs by taking human codon usage as a reference, it was revealed similar pattern of adaptation to the human cellular system of SARS-CoV-2 and the closely related pangolin-CoV (see Fig.…”

Natural Selection Plays an Important Role in Shaping the Codon Usage of Structural Genes of the Viruses Belonging to the Coronaviridae Family

“…A recent paper by Tort et al suggested mutational pressure to be the major factor responsible for shaping the codon usage pattern (CUP) in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [16]. In another study by Anwar et al, natural selection and other factors were considered to shape the CUP of the SARS-CoV-2 [17]. A study by Dulicca et al demonstrated the influence of both mutational and selectional pressures in shaping the CUP of the SARS-CoV-2 genes [18].…”