Flavinkins (@Flavinkins)

https://arxiv.org/abs/2104.01533 https://www.pnas.org/doi/10.1073/pnas.0808116105 Also, guess which kind of process lead to coronavirus genomes with “complex recombination history” between closely related sample sequences (<5% different to each other) and with a “complex recombination history” ? The synthesis of consensus genomes from such collection of genomes, especially on the backbone. Dependent on which specific SNV amongst the genomes used as the templates were selected in the final consensus for each genomic position, and especially when the genomes used in the consensus weren’t very divergent from each other, the final consensus genome would look like the result of “Complex recombination events” between “multiple genomes in nature” which may be the direct or an extremely close (only difference is in time) source of the sequences of which the final consensus genome was constructed. As all fragments of the final consensus virus were obtained from genomes sequenced from bats, (and as such all substitutions of the consensus genome compared from other bat isolate genomes were obtained from a bat isolate,) this will also generate substitutional patterns that is highly consistent with a bat host environment—and not with anything else. Cellular passages that causes less than 10 mutations in the genome, which is sufficient for P681 in the FCS and Q498 in the RBD (if you take different cell passaged strains, RFLP with FauI to ensure FCS is not lost (should you want self-spreading https://archive.ph/71Di3 ), and find one that don’t cause mice to get sick; just the number of passages needed to evaluate growth and locate hypopathogenic plaques), however will not show up as significant on the substitutional profile. Especially if only partial genomes were generated from each sample—you need to stitch together the contigs from each sample to get a full genome that you can then rescue. This become especially problematic if the genome(s) you used were from metagenomic sequencing results—any chimeric assemblies generated during the original sequencing processes (especially if more than 1 samples were used in the initial sequencing and assembly, as in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491849/) would end up in the final infectious clone, especially if multiple genome isolates were used together to generate and then rescue an infectious clone. The result is a “highly recombinant” genome, where the “recombination junctions” are generated from both the chimeric initial assemblies from pooled or multiple samples, and from the nucleotide selection process used during the creation of consensus genomes from multiple assemblies. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004420 https://www.cell.com/cell-reports/pdf/S2211-1247(18)31448-7.pdf It is not just bat viruses—the CAS is apparently already highly proficient at rescuing metagenomic viruses nowadays, that “ We are working on virus isolation and viral particles rescue via reverse genetic system, hoping to throw light on these confused puzzles.” from pooled samples. https://www.virosin.org/article/doi/10.1007/s12250-020-00319-x https://web.archive.org/web/20210228211633/https://www.virosin.org/article/doi/10.1007/s12250-020-00319-x Assembly artifacts in this case, will definitely become “recombination junctions” in the resulting rescued virus. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010268 Another process that was adopted by the CAS, that is, the rescue of viruses from incomplete genomes through the complementation of the missing parts of the genome using parts from other closely related viruses, also lead to the appearance of apparent “recombination junctions” in parts of the genomes that were spliced together during the rescue attempt. @SherlockGNomes