Codon Usage and Phenotypic Divergences of SARS-CoV-2 Genes.

Maddalena Dilucca,Sergio Forcelloni,Andrea Giansanti,Alexandros G Georgakilas,Athanasia Pavlopoulou

doi:10.3390/v12050498

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a high mortality rate, and has spread around the world. To gain an understanding of the evolution of the newly emerging SARS-CoV-2, we herein analyzed the codon usage pattern of SARS-CoV-2. For this purpose, we compared the codon usage of SARS-CoV-2 with that of other viruses belonging to the subfamily of Orthocoronavirinae. We found that SARS-CoV-2 has a high AU content that strongly influences its codon usage, which appears to be better adapted to the human host. We also studied the evolutionary pressures that influence the codon usage of five conserved coronavirus genes encoding the viral replicase, spike, envelope, membrane and nucleocapsid proteins. We found different patterns of both mutational bias and natural selection that affect the codon usage of these genes. Moreover, we show here that the two integral membrane proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their corresponding genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins (S), although they are regarded as are important targets for the development of vaccines and antiviral drugs, tend to evolve faster in comparison to the two genes mentioned above. Overall, our results suggest that the higher divergence observed for the latter three genes could represent a significant barrier in the development of antiviral therapeutics against SARS-CoV-2.

Highlights

The name “coronavirus” is derived from the Greek κoρωνα, due to the viruses’ typical shapes being crown-like
To investigate the factors determining the codon usage patterns of SARS-CoV-2 and other coronaviruses, several analytical methods were used in our study
In line with the common nucleotide composition of other RNA viruses such as SARS, our results show that SARS-CoV-2 has a high AU content and a low GC content

Summary

Introduction

The name “coronavirus” is derived from the Greek κoρωνα, due to the viruses’ typical shapes being crown-like. The first complete genome of a coronavirus (mouse hepatitis virus—MHV), a positive sense, single-stranded RNA virus, was first reported in 1990 [1]. It belongs to the family Coronaviridae and ranges from 26.4 (ThCoV HKU12) to 31.7 (SW1) kb in genome length [2], having the largest genome among all known RNA viruses, with G + C contents varying from 32% to 43% [3]. Viruses 2020, 12, 498 sub-family consists of four genera based on their genetic properties: Alphacoronavirus, Betacoronavirus (subdivided in subgroups A, B, C and D), Gammacoronavirus and Deltacoronavirus. We have focused on 30 coronavirus (CoV) genomes: 28 viruses from Woo et al Coronaviruses can infect humans and diverse animal species, including swine, cattle, horses, camels, cats, dogs, rodents, birds, bats, rabbits, ferrets, minks, snakes and other wildlife animals.

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