Journal of Vaccines & Vaccination

Preliminary Estimates of the Mutational Frequencies of Individual Genes in SARS-Cov-2 Genome

Wenfa Ng^* Department of Biomedical Engineering, National University of Singapore, Novena, Singapore
^*Correspondence: Wenfa Ng, Department of Biomedical Engineering, National University of Singapore, Novena, Singapore, Email:

Received: 05-Nov-2021 Published: 26-Nov-2021

Description

Mutations are common in viral genes and genomes as they are the bedrock on which the virus evolves to evade immune surveillance and attack, as well as adapt to new host environment [1-4].

Hence, it is important to gain an understanding of the mutational frequencies of each gene in the genome of a virus in order to appreciate its evolutionary trajectory, and predict how it will evolve in future [5-7].

This work sought to obtain preliminary estimates of the mutational frequencies of each gene in the genome of SARSCoV- 2 to help decipher the underlying reasons why there have been frequent emergence of variants of concern.

A total of 10 different genomes of the virus belonging to individual isolates were downloaded from European NucleotideArchive.

The genome sequence of each isolate is used as template on which different genes in the reference genome of SARSCoV- 2 downloaded from Genbank was aligned.

Mutation in gene is called when there is no exact match in the isolate’s genome sequence for a particular gene in the reference genome. Mutational data was thus aggregated over ten isolates and help produce the mutational frequency table. All computations and bioinformatics analysis were conducted using MATLAB.

Results presented in Table 1 reveal that five genes suffer high mutational burden compared to other genes in the genome of SARS-CoV-2. These genes are ORF1ab encoding RNAdependent RNA polymerase, spike protein, ORF3a protein, nucleocapsid protein and ORF8 protein. In particular, RNAdependent RNA polymerase and spike protein suffer the highest mutational burden at 90% mutational frequency, which holds significant implications for vaccine development and containing the spread of variants of concern. Specifically, mutations in RNA-dependent RNA polymerase changes the shape and possibly the functional efficiency of the enzyme, which suggests that errors will creep in during transcription of large genes that may increase the pathogenic potential of the virus. In the case of spike protein, mutations in this protein will alter its shape, and thwart efforts to develop neutralizing antibodies for this antigen or in vaccine development.

Table 1: Mutational frequency of each gene in the genome of SARS-CoV-2.

Conclusion

Overall, mutations drive the evolution of virus in unpredictable ways. Although the course of evolution can be shaped by natural selection pressure in the lab, the same cannot be said of virus in the environment exposed to changing environmental conditions and host factors. This work probes the mutational frequency of each gene in the genome of SARS-CoV-2 and reveals that five genes are of highest mutational burden. These genes are ORF1ab, spike protein, ORF3a protein, ORF8 protein, and nucleocapsid protein. Of particular concern is the exceedingly high mutational frequency (90%) of ORF1ab (RNA-dependent RNA polymerase) and spike protein, which explains the frequent emergence of new variants of concern with higher infectivity, as well portends a future in which new variants will emerge if we fail to contain the spread of the virus, as mutations potentially occur with each replication of the virus in cells.

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