[Causality1]

I would enjoy a deeper dive on the reasons why the covid genome doesn't tell us whether it's zoonotic or lab-created. In my ignorance I figured that genetic modification left signatures in the genome that could be recognized.

[sampo]

One way to increase the virulence of a virus in lab, is to let it infect cells in cell culture, and replicate for a large number of generations. This is sort of natural evolution, guided in a lab, and doesn't involve genetic modification.

[angelzen]

We'll never know for sure. Which is too bad, because the plan of "Let's comb remote caves for hundreds of dangerous pathogens, bring them to a lab in the middle of a 10M metropolis, then perform gain-of-function research on them" is as nutty as it sounds.

[noahtallen]

I don’t know if it’s that nutty! “Let’s study the most dangerous pathogens” sounds like a good idea to me. So the nutty part would be doing it in a city, but would that actually make a huge difference compared to a remote lab? If it got out of a remote lab, one can imagine it would ultimately end up spreading quite far exponentially, even if it would take slightly longer to reach a metropolis.

Seems to me the main thing would be ensuring foolproof protection from anything escaping at the lab — which obviously was lacking if the theory is true. So the idea seems fine to me.

[bradknowles]

If you think anything can be made foolproof, then all I can say is that you must not yet have met a sufficiently foolish fool.

The one and only job that any fool has is to defeat any so-called “foolproof” system that they come into contact with. And, taken as a whole, history has proven that they are unbeatable.

[Metacelsus]

Typically serial passage decreases the virulence (since there's no selection pressure from the immune system, mutations accumulate in immune evasion genes). But if it's an animal virus, this is a good way to evolve it to infect human cells.

[Obi_Juan_Kenobi]

The only 'signature' one could expect is from flanking sequences. Some viruses, transposons, and bacteria leave such sequence, but it is not universal. And we're talking about organisms here, whole genomes of many mega/giga-bases vs. viruses of mere kilobases. Even knowing what to look for, it can be quite difficult: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940375/

In a lab setting, a simple restriction digest and recombination can yield a modification with no signature, or else you can generate SNPs with PCR. And you would want to, as viral genomes are so small, often with overlapping ORFs, that you don't have much room to leave a bunch of junk around.

There is no signature. What we can do is look at sequence similarity and decide how probable or improbable a given sequence combination is from the viral genome sampling available. It's a lot of handwavy Bayesian statistics, based on incomplete sampling.

[achenatx]

You cant really tell from the genetics. You can chop and insert any arbitrary sequence into RNA/DNA.

Instead what they do is look at the animal population in the region for highly related or identical versions. If it was natural transmission you would expect animals to be infected with a strain that is extremely similar to the virulent strain.

What this is saying is that there has been no discovery of an intermediate host which has a highly related genome. This would happen if the version that spread in humans had been incubated in a lab for a long time and had undergone enough mutations in the lab to be very dissimilar to natural versions.

<<Investigators now face the reverse situation for tracing the origins of SARS-CoV-2: a paucity of evidence and a cold trail. Closely related bat SARSr-CoVs have been identified, but there is still no sign of an intermediate host 1.5 years into the pandemic. The closest bat virus relatives have been found in Yunnan province about a thousand miles away from Wuhan in Hubei province [17–19]. >>