Slack / Private Message Drop — page 593

collected from the Market) were in this cluster [7]. Although the M type was the dominant type during the early outbreak of COVID-19 in Wuhan, the non-Market genotypes from four patients forms the second cluster that also co-existed with M type cluster at that time. Two of them were ancestral type and the other two had their own unique mutations." [2021-03-14 10:28:57] [Robert Garry] https://www.biorxiv.org/content/10.1101/2020.08.27.270637v1.full.pdf The nS mutation T28144C: ORF8: T251C, L84S. Not trivial. [2021-03-14 11:38:46] [Andrew Rambaut] From our nomenclature paper: https://www.nature.com/articles/s41564-020-0770-5 ```At the root of the phylogeny of SARS-CoV-2 are two lineages that we simply denote as lineages A and B. The earliest lineage A viruses, such as Wuhan/WH04/2020 (EPI_ISL_406801), sampled on 5 January 2020, share two nucleotides (positions 8,782 in ORF1ab and 28,144 in ORF8) with the closest known bat viruses (RaTG13 and RmYN02). Different nucleotides are present at those sites in viruses assigned to lineage B, of which Wuhan-Hu-1 (GenBank accession no. MN908947) sampled on 26 December 2019 is an early representative. Hence, although viruses from lineage B happen to have been sequenced and published first8,9,10, it is likely (based on current data) that the most recent common ancestor (MRCA) of the SARS-CoV-2 phylogeny shares the same genome sequence as the early lineage A sequences (for example, Wuhan/WH04/2020). ``` [2021-03-14 11:40:56] [Andrew Rambaut] But actually the haplotype that was WA1 in Seattle (a traveller from Wuhan) is one SNP closer to the bat viruses and I think that may be the earliest sampled haplotype. [2021-03-14 11:47:59] [Robert Garry] Yes - the authors rediscovered what you already taught. The smoking raccoon dog/grate data puts this into a somewhat new context. [2021-03-14 11:57:09] [Robert Garry] https://pubmed.ncbi.nlm.nih.gov/32912998/ So this paper takes on even more significance... [2021-03-14 13:41:32] [Robert Garry] So - I am obviously struggling to get this straight - grate data ([high levels of virus in the sewer] suggests that lineage B SC2 infected raccoon dog or dogs and perhaps other animals were in the Market. These lineage B viruses spread to 30 or more ppl who were linked to the market and were already accumulating mutations. Lineage A virus differs from lineage B at positions 8,782 in ORF1ab and 28,144 in ORF8. Lineage A is more like bat viruses and had infected several other ppl in Wuhan, but not linked to this market - one of those ppl flew to Seattle and started the WA1 lineage. WA1 lineage died out in the US. WA1 is lineage A and has bat-like T8782 and C28144 plus another bat-like snp and therefore may be even closer to the MCRA than the other early sequenced lineage A viruses from Wuhan. WA2 (also lineage A) was introduced separately. WA1 did not give rise to WA2. [2021-03-14 13:53:03] [Robert Garry] Lots of questions. 1. How different were the lineage B SC2s from the humans and environmental samples at the market? Market lineage B SC2s had apparently accumulated some mutations (the Chen paper says 14). 2. Did the SC2s from the environmental samples give rise to the samples in the early Wuhan patients linked to the market or perhaps is it the other way around or perhaps no way to tell? 3. Is it fair to say that lineage A likely gave rise to lineage B? [2021-03-14 14:09:30] [Robert Garry]