SARS-COV2 Could Take Approximately 30 Years to Emerge From Bat to Human Host
Estimating the time frame to evolute SARS-COV2 from RaTG13 is intricate and depends on mutation rate and other factors. Especially the Retrovirus evolution is complicated as it depends on the forces that drive the mutation rate per site nucleotide in the genome for its extra step of reverse transcription. The optional mutation rate is context dependent at which rate the errors are made during replication of the viral genome. Apart from depending on the size of the genome, it also depends on the fidelity of RDRP (RNA Directed RNA Polymerase), proofreading activity and selection pressure (13). RDRP could be very different for each Retrovirus, as for example, SARS-COV2 and Ebola RDRP are completely different (no significant similarities, data not shown) but SARS-COV2 RDRP bears considerable identity with SARS-COV (1, 2). Again, all Retrovirus do not possess proofreading activities, but Coronavirus have strong proofreading activities. Thus, a general consensus about a mutation rate in SARS-COV2 cannot be reached although the mutation rate for positive strand Retrovirus have been estimated as 10-4 to 10-6/s(substitution)/n(nucleotide) /c (cell infection). Cell infection estimates the viral generation) (13, 14).
RaTG13 of bat is believed to be the ancestor of SARS-COV2 that bears 96.3% nucleotide identities, which overall corresponds ~1106 nucleotides (100-96.3=3.7/100 x 29903) substitutions assuming the genome size of SARS-COV2 is 29903bases (2). Thus, a huge number (~1106) of nucleotide substitutions occurred in RATG13 of bat to become present-day SARS-COV2 of human.
After the emergence of SARS-COV2 since December, 2019 a large number of genomic sequences are deposited in various database and several reports about their phylogeny has been elucidated(4, 15-17). Pairwise sequence analysis of eighty-three SARS-COV2 genomic sequences from collection date of December, 2019 to April 2020 by BLAST with reference genome, we calculated the average mutation rate [Fig. 1A ] of the virus to get an estimation that how rapidly the virus was changing. The average nucleotide changes occurred ~2 bp/month [Fig1B ] in January to 4.89 bp/month in April. The typical average nucleotide substituted from December 2019 to April (1st-10th) for 4 months is 11.94 ~12 nucleotides. If this observed mutation after selection continues at this rate in human host, a simple extension of this calculation gives us 36 nucleotide (12 x 12/4) substitutions per year, which ultimately takes 30.7 years (1106 nucleotide/36) to evolute present-day SARS-COV2 from RaTG13 of bat.