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.