Interesting paper discussing the difficulty of rooting the SARS-CoV-2 tree - which is something we have been interested in too.

Most analyses root on e.g., Hu-1, but it appears that e.g., WA1 (lineage) may actually be a more appropriate root IMO.

https://academic.oup.com/mbe/advance-article/doi/10.1093/molbev/msaa316/6028993

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One critical issue with the paper - they mention that rooting on non-Wuhan sequences would be inappropriate as that is inconsistent with epidemiological evidence (see 👇). That's not true - there's a very strong sampling bias early in the epidemic...

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... which means that (early) sequences observed outside Wuhan could very likely have circulated (uncaptured) in Wuhan as well.

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This also means that choosing WA1 (lineage) as a root doesn't actually place the root in Washington - WA1 is just a representative sequence of an earlier (basal) lineage that circulated in China (mid-November / early-December?) - but was not captured by sequencing.

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We're clearly missing a lot of the early divergence in Wuhan/China, which means that properly rooting the tree will forever be difficult - unless we manage to capture some really early lineages / intermediate host sequences.

Discuss... Midpoint rooting, anyone...?

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