Preprint Short Note Version 1 Preserved in Portico This version is not peer-reviewed

Evolution of Nucleotide Composition in the SARS-CoV-2 Lineage: Implications for Vaccine Design

Version 1 : Received: 20 June 2020 / Approved: 21 June 2020 / Online: 21 June 2020 (10:16:01 CEST)

A peer-reviewed article of this Preprint also exists.

Subramanian, S. The Long-Term Evolutionary History of Gradual Reduction of CpG Dinucleotides in the SARS-CoV-2 Lineage. Biology 2021, 10, 52. Subramanian, S. The Long-Term Evolutionary History of Gradual Reduction of CpG Dinucleotides in the SARS-CoV-2 Lineage. Biology 2021, 10, 52.


The worldwide outbreak of a novel coronavirus, SARS-CoV-2 has caused a pandemic of respiratory disease. Due to this emergency, researchers around the globe have been investigating the evolution of the genome of SARS-CoV-2 in order to design vaccines. Here I examined the evolution of GC content of SARS-CoV-2 by comparing the genomes of the members of the group Betacoronavirus. The results of this investigation revealed a highly significant positive correlation between the GC contents of betacoronaviruses and their divergence from SARS-CoV-2. The betacoronaviruses that are distantly related to SARS-CoV-2 have much higher GC contents than the latter. Conversely, the closely related ones have low GC contents, which are only slightly higher than that of SARS-CoV-2. This suggests a systematic reduction in the GC content in the SARS-CoV-2 lineage over time. The declining trend in this lineage predicts a much-reduced GC content in the coronaviruses that will descend/evolve from SARS-CoV-2 in the future. Due to the three consecutive outbreaks (MERS-CoV, SARS-CoV and SARS-CoV-2) caused by the members of the SARS-CoV-2, the scientific community is emphasizing the need for universal vaccines that are effective across many strains including those, that will inevitably emerge in the near future. The reduction in GC contents implies an increase in the rate of GC→AT mutations than that the mutational changes in the reverse direction. Therefore, understanding the evolution of base composition and mutational patterns of SARS-CoV-2 could be useful in designing broad-spectrum vaccines that could identify and neutralize the present and future strains of this virus.


Nucleotide composition; mutational change; GC to AT; COVID-19; SARS-CoV-2; Vaccine design


Biology and Life Sciences, Biochemistry and Molecular Biology

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