>Fixation relies on selection, which is entirely different in a laboratory environment than in a population with immune systems.

This is actually extremely controversial. There's a great deal of evidence that random walks are more important than selection in fixation events. Does selection play a role? Yes! Definitely! But the evidence is mounting and almost at consensus that random chance is actually what dictates most fixation events. It just can't be /deleterious/ but it does not have to be /helpful/ to fix. The evidence shows that most mutations, on median, are neutral or slightly deleterious. But the ones that are beneficial are so beneficial that the average is neutral-to-net-positive. A lot more of it is actually stochastic than you think! A lot of the transmission between hosts, for example, is stochastic and not selective.

See these reviews/studies from Bloom, Audino, etc:

-https://elifesciences.org/articles/35962

-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173453/

-https://www.cell.com/cell-host-microbe/pdf/S1931-3128(18)301...

-https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372249/

-https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0014-3820....

-https://journals.plos.org/plospathogens/article?id=10.1371/j...

This is why it's less easy to maintain a virus at the proper S/NS ratio in the lab. It becomes too stochastic. too little selection. So your mad scientist would have to have extremely few viral genera.

You say every gene evolves more slowly than non-coding, which is true. but synonymous mutations happen at the same rate as one would expect it to occur in both.

Are you trying to say it isn't ever going to happen? From what I'm reading, there's actually no reason to believe the CGG in that site is fixed in any way. It's not always CGG. In fact, it rarely is in CoV-2 isolates. Maybe that was a fluke of the sequencer or the isolate?

Wow, now I'm starting to think Yuri just didn't do his homework.

This paper seems to suggest it uses codons extremely similarly to its neighbors, and that it doesn't use CGG often or at all. It says never: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173453/

but that's just in the isolates they're analyzing.

"All human coronaviruses analyzed in this study did not use two synonymous codons (CGC, CGG) for arginine as well as CCG for proline and UGA for stop codon at all"

The money shot is in figure B. I think Yuri in his write up is just using a random one-off sequence of SARS-2 that showed up /later/ in the pandemic. It isn't in the earliest released sequences from Korea or Wuhan or Iran (https://www.ncbi.nlm.nih.gov/nuccore/NC_045512.2) (https://www.ncbi.nlm.nih.gov/nuccore/MT126746.1) (https://www.ncbi.nlm.nih.gov/nuccore/MT121215.1). It only shows up in later sequences. It could be a result of adaptation to humans for the weird non-human cleavage site.

I couldn't find CGG in the cleavage site sequence anywhere in the early pandemic. Not in any of the earliest papers.

I could only find it in clinical sequences from later on in the pandemic, suggesting it may have been a random mutant that fixed /after/ the emergence into humans. Which pokes a big ol hole in the idea that it represents a smoking gun of genetic manipulation:

-https://www.ncbi.nlm.nih.gov/nuccore/MW269555.1
-https://www.ncbi.nlm.nih.gov/nuccore/MW672572.1

I shouldn't have taken it as a given that CGGCGG was actually there in the beginning. Looks like it wasn't It certainly isn't in the refseq.

And the thing I'm asking here is: Are you really saying you think the lab leak is /as probable/ as the zoonotic crossover? Given that the A) the CGGCGG wasn't even there when the crossover happened, B) the probabilistic arguments I've made above, and C) the fact that you can't provide any actual evidence of a mechanism? I gave you lots of mechanisms and examples of how it would happen in nature. Why is one not more likely than the other?