From SARS and MERS CoVs to SARS‐CoV‐2: Moving toward more biased codon usage in viral structural and nonstructural genes

Kandeel, Mahmoud; Ibrahim, Abdelazim; Fayez, Mahmoud; Al‐Nazawi, Mohammed

doi:10.1002/jmv.25754

Cited by 176 publications

(164 citation statements)

References 33 publications

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“…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].…”

Section: Resultssupporting

confidence: 92%

Characterization of Codon Usage Pattern in SARS-CoV-2

Hou¹

2020

Preprint

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The outbreak of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed significant threats to international health. The genetic traits as well as evolutionary processes in this novel coronavirus are not fully characterized, and their roles in viral pathogenesis are yet largely unknown. To get a better picture of the codon architecture of this newly emerging coronavirus, in this study we perform bioinformatic analysis, based on publicly available nucleotide sequences of SARS-CoV-2 along with those of other members of human coronaviruses as well as non-human coronaviruses in different hosts, to take a snapshot of the genome-wide codon usage pattern of SARS-CoV-2 and uncover that all over-represented codons end with A/U and this newly emerging coronavirus has a relatively low codon usage bias, which is shaped by both mutation pressure and natural selection. Additionally, there is slight variation in the codon usage pattern among the SARS-CoV-2 isolates from different geo-locations. Furthermore, the overall codon usage pattern of SARS-CoV-2 is generally similar to that of its phylogenetic relatives among non-human betacoronaviruses such as RaTG13. Taken together, we comprehensively analyze the characteristics of codon usage pattern in SARS-CoV-2 via bioinformatic approaches. The information from this research may not only be helpful to get new insights into the evolution of SARS-CoV-2, but also have potential value for developing coronavirus vaccines.

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Section: Resultssupporting

confidence: 92%

Characterization of Codon Usage Pattern in SARS-CoV-2

Hou¹

2020

Preprint

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“…A strong bias toward A and U ending codons was found. This in agreement with very recent studies revealing a significant predominance of A and U at third codon positions in CoV genomes (Sheikh et al, 2020;Wang et al, 2018;Kandeel et al, 2020). These results also suggest that these differences are related to codon usage preferences.…”

Section: Discussionsupporting

confidence: 93%

A comprehensive analysis of genome composition and codon usage patterns of emerging coronaviruses

2020

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1 These authors contributed equally to this work. Highlights• A comprehensive genome and codon usage analysis of SARS-CoV-2 was performed.• SARS-CoV-2 has a distinct genome composition in relation to other βCoV strains.• The overall codon usage in SARS-CoV-2 is slightly biased.• Most of the highly frequent codons are A-and U-ending codons.• Different codon preferences in SARS-CoV-2 genes in relation to human ones were found.• These differences are due to codon usage preferences. J o u r n a l P r e -p r o o f Abstract An outbreak of atypical pneumonia caused by a novel Betacoronavirus (βCoV), named SARS-CoV-2 has been declared a public health emergency of international concern bythe World Health Organization. In order to gain insight into the emergence, evolution and adaptation of SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of βCoV circulating in China was performed. A biased nucleotide composition was found for SARS-CoV-2 genome. This bias in genomic composition is reflected in its codon and amino acid usage patterns. The overall codon usage in SARS-CoV-2 is similar among themselves and slightly biased. Most of the highly frequent codons are A-and U-ending, which strongly suggests that mutational bias is the main force shaping codon usage in this virus. Significant differences in relative synonymous codon usage frequencies among SARS-CoV-2 and human cells were found. These differences are due to codon usage preferences.

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“…The unusually skewed distribution of nucleotide frequencies in synonymous sites in SARS-CoV-(Kandeel, et al 2020), along with high divergence, complicates the estimation of synonymous divergence in SARS-CoV-2 and related viruses. In particular, in the third codon position the nucleotide frequency of T is 43.5% while it is just 15.7% for C. This resulting codon usage is not optimized for mammalian cells (e.g, Chamary, et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Synonymous mutations and the molecular evolution of SARS-Cov-2 origins

Wang

Pipes

Nielsen

2020

Preprint

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1Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely 2 related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and 3 RmYN02. However, there is a segment of high amino acid similarity between human CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of 5 the spike protein, a pattern that can be caused by either recombination or by convergent 6 amino acid evolution driven by natural selection. We perform a detailed analysis of the 7 synonymous divergence, which is less likely to be affected by selection than amino acid 8 divergence, between human SARS-CoV-2 and related strains. We show that the 9 synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than 10 between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for 11 the recombination hypothesis. However, the synonymous divergence between pangolin 12 strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent 13 recombination between them, instead it suggests a recombination into RaTG13. We also 14 find a 14-fold increase in the d N /d S ratio from the lineage leading to SARS-CoV-2 to the 15 strains of the current pandemic, suggesting that the vast majority of non-synonymous 16 mutations currently segregating within the human strains have a negative impact on viral 17fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-18CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% 19 C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively. 20 21 a coronavirus (Lu, et al. 2020; Zhang and Holmes 2020), Severe acute respiratory syndrome 1 coronavirus 2 (SARS-CoV-2), an RNA virus with a 29,891 bp genome consisting of four major 2 structural genes (Wu, et al. 2020; Zhou, Yang, et al. 2020). Of particular relevance to this study 3 is the spike protein which is responsible for binding to the primary receptor for the virus, 4 angiotensin-converting enzyme 2 (ACE2) (Wan, et al. 2020; Wu, et al. 2020; Zhou, Yang, et al. 5 2020). 6Human SARS-CoV-2 is related to a coronavirus (RaTG13) isolated from the bat 7Rhinolophus affinis from Yunnan province of China (Zhou, Yang, et al. 2020). RaTG13 and the 8 human strain reference sequence (Genbank accession number MN996532) are 96.2% identical 9and it was first argued that, throughout the genome, RaTG13 is the closest relative to human 10 SARS-CoV-2 (Zhou, et al. 2020). Zhang, et al. 2020 showed that RaTG13 and SARS-CoV-2 11 were 91.02% and 90.55% identical ,respectively, to coronaviruses isolated from pangolins 12 (Pangolin-CoV), which therefore form a close outgroup to the SARS-CoV-2+RaTG13 clade . 13 Furthermore, five key amino acids in the receptor-binding domain (RBD) of spike were identical 14 between SARS-CoV-2 and Pangolin-CoV, but differed between those two strains and RaTG13. 15 (Lam, et al. 2020) independently made similar observations and additionally showed that when 16 analyzing...

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From SARS and MERS CoVs to SARS‐CoV‐2: Moving toward more biased codon usage in viral structural and nonstructural genes

Cited by 176 publications

References 33 publications

Characterization of Codon Usage Pattern in SARS-CoV-2

Characterization of Codon Usage Pattern in SARS-CoV-2

A comprehensive analysis of genome composition and codon usage patterns of emerging coronaviruses

Synonymous mutations and the molecular evolution of SARS-Cov-2 origins

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