Peer Review #1 of "Excessive G–U transversions in novel allele variants in SARS-CoV-2 genomes (v0.2)"

Abstract

Background. SARS-CoV-2 is a novel coronavirus that causes COVID-19 infection, with a closest known relative found in bats. For this virus, hundreds of genomes have been sequenced. This data provides insights into SARS-CoV-2 adaptations, determinants of pathogenicity and mutation patterns. A comparison between patterns of mutations that occurred before and after SARS-CoV-2 jumped to human hosts may reveal important evolutionary consequences of zoonotic transmission. Methods. We used publically available complete genomes of SARS-CoV-2 to calculate relative frequencies of single nucleotide variations. These frequencies were compared with relative substitutions frequencies between SARS-CoV-2 and related animal coronaviruses. A similar analysis was performed for human coronaviruses SARS-CoV and HKU1. Results. We found a 9-fold excess of G to U transversions among SARS-CoV-2 mutations over relative substitution frequencies between SARS-CoV-2 and a close relative coronavirus from bats (RaTG13). This suggests that mutation patterns of SARS-CoV-2 have changed after transmission to humans. The excess of G to U transversions was much smaller in a similar analysis for SARS-CoV and non-existent for HKU1. Remarkably, we did not find a similar excess of complementary C to A mutations in SARS-CoV-2. We discuss possible explanations for these observations.