Either SARS-CoV-2 evolved from BANAL + a PRRA insertion, or it was engineered
Debate about covid’s origin and lab leak tends to dissolve into a jumble of more or less fuzzy theories: Huanan market civets, and DEFUSE, and what about that database they shut down in September? But I’ll briefly argue here (as I have on Twitter) that there are at least two basic facts we can conclusively infer from public evidence.
1. SARS-CoV-2 (SC2)’s origin, natural or artificial, involved the introduction of a 12-nucleotide PRRA furin cleavage site (FCS) into a close relative of BANAL-52.
This is the only way to make sense of the extreme similarity between SC2 and BANAL-52 in the S1/S2 region of the genome both immediately before and after the FCS. See Sherlock G.Nomes 2021:
…As well as Lytras 2020, no lab leak conspiracist (note that BANAL-52, not yet known when this was published, is even closer to SC2 than RaTG13 is):
…And Temmam et al 2022:
Alternative genetic histories of SC2 and how it evolved the FCS have been proposed, eg in Sander et al 2022. But if SC2’s immediate ancestor wasn’t a BANAL strain, how else could they have ended up so similar around the FCS? This seems like a no-brainer: SC2 is very closely related to BANAL-52 and therefore, since BANAL-52 lacks an FCS, the FCS must have appeared after its evolutionary divergence from BANAL-52.
(Unless someone wants to argue that the BANAL strains evolved from SC2, losing its FCS. I don’t think anyone’s arguing that.)
So in short: it doesn’t matter if there are natural mechanisms by which SC2 could have evolved the FCS from some non-BANAL strain, like RmYN02; that can’t be what happened. Because if it had, SC2 being a near-match to BANAL-52 around the FCS would be the world’s biggest coincidence.
It is possible, for example, that some as-yet-undiscovered descendant or cousin of BANAL-52 acquired the FCS, and SC2 descended from that. What is not plausible is that SC2 (in particular, its FCS region) descended from a lineage less similar to SC2 than BANAL-52 is.
(As an aside, I wouldn’t expect SC2 to be identical to BANAL-52 — or whichever strain the FCS was introduced to — anyway, because I think there’s good evidence that post-FCS SC2 was preadapted to humans: eg via serial passaging through humanized mice. But that’s a separate debate.)
2. If SC2 wasn’t engineered, its origin involved the natural evolution of the 12-nucleotide PRRA FCS in BANAL-52 or a close relative. So it’s worth trying to understand: how might this happen naturally?
“Twelve point mutations” does not seem credible. Recombination is also hard to understand given, again, the close similarity of the regions both before and after the FCS. But perhaps Sander et al’s “insertion due to external stem loop structures”?
Answering this question, “What natural process could introduce a 12-nucleotide sequence into an otherwise almost-unchanged stretch of the genome,” is too technical for me. I welcome answers!
But my point is, there are only two hypotheses worth exploring here. Either:
a) The FCS was introduced into a BANAL-52 neighbor through some natural process, that preserved the sequence before and after; or
b) The FCS was inserted manually, ie, in a lab.
My qualifications: basically none lol I’m just another guy on the Internet. I’ve probably made some silly mistakes above, though I’m skeptical they entirely refute my point. I encourage you to send along any responses/corrections on the bird app. And I encourage civility, good faith + default assumption of good faith, etc. Yes it’s frustrating to have to explain basic stuff to us amateurs but I’ll be surprised if the eventual full history of covid concedes no successes to the amateurs.
