Variation in synonymous nucleotide composition among genomes of sarbecoviruses and consequences for the origin of COVID-19

The subgenus Sarbecovirus includes two human viruses, SARS-CoV and SARS-CoV-2, respectively responsible for the SARS epidemic and COVID-19 pandemic, as well as many bat viruses and two pangolin viruses. Here, the synonymous nucleotide composition (SNC) of Sarbecovirus genomes was analysed by examining third codon-positions, dinucleotides, and degenerate codons. The results show evidence for the eight following groups: (i) SARS-CoV related coronaviruses (SCoVrC including many bat viruses from China), (ii) SARS-CoV-2 related coronaviruses (SCoV2rC; including five bat viruses from Cambodia, Thailand and Yunnan), (iii) pangolin sarbecoviruses, (iv) three bat sarbecoviruses showing evidence of recombination between SCoVrC and SCoV2rC genomes, (v) two highly divergent bat sarbecoviruses from Yunnan, (vi) the bat sarbecovirus from Japan, (vii) the bat sarbecovirus from Bulgaria, and (viii) the bat sarbecovirus from Kenya. All these groups can be diagnosed by specific nucleotide compositional features except the one concerned by recombination between SCoVrC and SCoV2rC. In particular, SCoV2rC genomes have less cytosines and more uracils at third codon-positions than other sarbecoviruses, whereas the genomes of pangolin sarbecoviruses show more adenines at third codon-positions. I suggest that taxonomic differences in the imbalanced nucleotide pools available in host cells during viral replication can explain the eight groups of SNC here detected among Sarbecovirus genomes. A related effect due to hibernating bats and their latitudinal distribution is also discussed. I conclude that the two independent host switches from Rhinolophus bats to pangolins resulted in convergent mutational constraints and that SARS-CoV-2 emerged directly from a horseshoe bat sarbecovirus.