[slibhb]

Your summary of the paper is unfair. From one of the author's blog:

> Recap: BsaI/BsmBI are particularly useful restriction enzymes to use if you wanted to study a bunch of chimeric coronaviruses like the close relatives of SARS-CoV-2. The SARS-CoV-2 BsaI/BsmBI cutting sites look regularly-spaced (ish). The maximum fragment length is in the bottom percentile of all CoVs digestions in the idealized fragment-number range, the bottom 0.07% for all type IIS digestions within the idealized range, and the number of fragments is also in the idealized range. The SARS-CoV-2 BsaI/BsmBI restriction map looks a lot more like known pre-COVID infectious clones than a wild coronaviruses. All sticky ends are unique & meet other nice criteria for good assembly. All mutations separating these sites from close relatives are silent, and there’s a significantly higher rate per nucleotide of silent mutations within BsaI/BsmBI recognition sites than the rest of the viral genome.

> The odds of meeting any one of these criteria vary, from 1%-0.07% of having such a small maximum fragment length to 1/250 to 1/100 million odds of having such high concentration of silent mutations within BsaI/BsmBI recognition sites. The odds of meeting every single one of these criteria are even smaller. Much smaller.

https://alexwasburne.substack.com/p/a-synthetic-origin-of-sa...

So it's not just "5 vs 2" sites, it's the spacing of the sites, the fact that the site mutations are silent, and the fact that the "sticky ends" are unique.

This paper should move your needle toward "synthetic origin". Similar to how some other papers published in the last few months (the wet market paper among them) should have moved your needle toward "natural origin".