The evolving proteome of SARS-CoV-2 predominantly uses mutation combination strategy for survival

The knowledge about SARS-CoV-2 proteome variations is important to understand its evolutionary tactics and in drug/vaccine design. An extensive analysis of 125,747 whole proteome reveals 7915 recurring mutations (involving 5146 positions) during December2019-November 2020. Among these, 10 and 51 are highly and moderately recurring mutations respectively. Ever since the pandemic outbreak, ∼50% new proteome variants evolve every month, resulting in 5 major clades. Intriguingly, ∼70% of the variants reported in January 2020 are due to the emergence of new mutations, which sharply declines to ∼ 40% in April 2020 and thenceforth, declines steadily till November 2020(∼10%). An exactly opposite trend is seen for variants evolved with cocktail of existing mutations: the lowest in January 2020(∼20%) and the highest in November 2020(80%). This leads to a steady increase in the average number of mutations per sequence. This indicates that the virus has reached the slow pace to accept new mutations. Instead, it uses a mutation combination strategy for survival.