Thread by @phylogenomics

So I just got through reading this article on origins of #COVID19 and have one aspect I want to discuss.

The origin of COVID: Did people or nature open Pandora’s box at Wuhan? - Bulletin of the Atomic Scientists thebulletin.org/2021/05/the-or… via @BulletinAtomic 1/n

First, I want to say, as I have said many times before, that I think working on the origins and trying to figure out if it came from a lab in some way or from "nature" is an important research area and I think the answer is still not resolved 2/n

And there are a lot of pieces to the story that are still muddled and unclear and need more work 3/n

However, I have one deep concern about a logical argument presented here (and sometimes elsewhere) that has been used to support the lab origin theories 4/n

The argument relates to the furin cleavage site observed in SARSCOV2 - and here Wade et al. basically argue that mutation could not have led to the multiple changes required to make this furin cleavage site & thus must be the result of recombination or purposeful manipulation 5/n

This argument presented in this article (and elsewhere) sounds remarkably close to a commonly used argument by Intelligent Design proponents generally known as "Irreducible Complexity" (e.g. see americanprogress.org/issues/religio…) 6/n

It is simply ridiculous to argue that mutation could not have created a small run of specific amino acids in a protein when at the same time we agree that mutation could have created things like the ribosome and such. 7/n

Again, I am not saying which theory on COVID19 origins is right or wrong here. But the logic presented in the Wade article that somehow one has to resort to either recombination or purposeful insertion is unsound. Mutation alone could easily have done this. 8/n

And using an irreducible complexity like argument to minimize mutation as a possible mechanism here is just unsound. Certainly, this does not in any way prove the "natural" origin theories but mutation needs to be considered and not thrown out for the wrong readsons 9/n

And just a reminder here - I am NOT saying I think the lab origin theory has been disproven at all. For example see this thread I posted about @alisonannyoung excellent reporting on lab leaks and why those are a major major issue

https://twitter.com/phylogenomics/status/1374016780344070153?s=20

What I am saying here is that the inference that I do not think it is sound to rule out normal mutational processes (coupled with natural selection) as a possible explanation for the additional bases / amino acids seen in one or more sections of SarsCOV2.

A really interesting and relevant preprint has been posted recently on @biorxivpreprint biorxiv.org/content/10.110… Insertions in SARS-CoV-2 genome caused by template switch and duplications give rise to new variants of potential concern

In this preprint the authors report "Two principal mechanisms appear to account for the inserts in the SARS-CoV-2 genomes, polymerase slippage and template switch that might be associated with the synthesis of subgenomic RNAs."

And that "We show that inserts in the Spike glycoprotein can affect its antigenic properties and thus have to be monitored"

And perhaps most importantly "Notably, the PRRA insert, the furin cleavage site that is one of characteristic features of SARS-CoV-2, resembles the long inserts analyzed here"

That is, in their analysis of the evolution of #SarsCoV2 they see many cases of insertions being added to genomes by natural means over very short time scales

So, basically, this says that insertions akin to what is seen in SarsCOV2 vs other coronaviruses occur relatively frequently over short time scales

And this is basically exactly what I was saying should be considered to counter the argument that the PRRA / Turin cleavage site could not have originated by natural means

This paper from Garushyants et al. seems really interesting and important