Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions

Carlos Farkas; Francisco Fuentes-Villalobos; Jose Luis Garrido; Jody J Haigh; María Inés Barría

The COVID-19 pandemic caused by a novel 2019 SARS coronavirus, known as SARS-CoV-2, that SARS-CoV-2 is a close relative of the RaTG13 bat-derived coronavirus (around 88% 53 identity) rather than of SARS-CoV-1 (79% identity) or middle east respiratory syndrome 54 coronavirus MERS-CoV (50% identity) (Lu et al. 2020 ). Due to this association with bat 55 coronaviruses, it was also argued that SARS-CoV-2 virus has the potential to spread into another 56 species, as bat coronaviruses do (Hu et al. 2018) . Recently, it was demonstrated that SARS-CoV-57 2 is closely related to a pangolin coronavirus (Pangolin-CoV) found in dead Malayan pangolins 58 with a 91.02% identity, the closest relationship found so far for SARS-CoV-2 (Zhang et al. 59 2020). In that study, genomic analyses revealed that the S1 protein of Pangolin-CoV is related 60 closer to SARS-CoV-2 than to RaTG13 coronavirus. Also, five key amino acid residues involved 61 in the interaction with the human ACE2 receptor are maintained in Pangolin-CoV and SARS-62 CoV-2, but not in RaTG13 coronavirus. Thus, it is likely that pangolin species are a natural 63 reservoir of SARS-CoV-2-like coronaviruses and SARS-CoV-2 will continue to evolve with 64 novel mutations, as the pandemic evolves. mutations in the helicase and orf1a proteins of the virus were found more frequently than others, 82 suggesting that these proteins are prone to evolve throughout natural selection. As proof of the 83 latter, a single nucleotide polymorphism (SNP) in an Australian sample causes a bona-fide stop 84 codon in the helicase protein, strongly suggest this protein will evolve on SARS-CoV-2 in the 85 future. As genetic drift prompts the mutational spectrum of the virus, we recommend frequently Washington study, hereafter referred as USA-WA) and remarkably, all of them displayed Since SARS-CoV-2 is an RNA virus that rapidly evolves after infection, these evolutionary 241 events will likely affect its fitness over time. In this study, we reveal the early mutational events