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 eigth 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 viruses, (iv) three bat viruses showing evidence of recombination between SCoVrC and SCoV2rC genomes, (v) two highly divergent bat viruses from Yunnan, (vi) the bat virus from Japan, (vii) the bat virus from Bulgaria, and (viii) the bat virus 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 are characterised by the lowest percentages of cyosine and highest percentages of uracil at third codon-positions, whereas the genomes of pangolin viruses exhibit the highest percentages of adenine at third codon-positions. I suggest that latitudinal and taxonomic differences in the imbalanced nucleotide pools available in host cells during viral replication can explain the seven groups of SNC here detected among Sarbecovirus genomes. A related effect due to hibernating bats is also considered. 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 virus.

A novel SARS-CoV-2 related coronavirus in bats from Cambodia

Knowledge of the origin and reservoir of the coronavirus responsible for the ongoing COVID-19 pandemic is still fragmentary. To date, the closest relatives to SARS-CoV-2 have been detected in Rhinolophus bats sampled in the Yunnan province, China. Here we describe the identification of SARS-CoV-2 related coronaviruses in two Rhinolophus shameli bats sampled in Cambodia in 2010. Metagenomic sequencing identified nearly identical viruses sharing 92.6% nucleotide identity with SARS-CoV-2. Most genomic regions are closely related to SARS-CoV-2, with the exception of a small region corresponding to the spike N terminal domain. The discovery of these viruses in a bat species not found in China indicates that SARS-CoV-2 related viruses have a much wider geographic distribution than previously understood, and suggests that Southeast Asia represents a key area to consider in the ongoing search for the origins of SARS-CoV-2, and in future surveillance for coronaviruses.