Flavinkins (@Flavinkins)

https://archive.ph/kM9rs Unfortunately, if you were to count the number of mutations on the CGG-CGG double codon in the SARS-CoV-2 genome (remember that the RR amino acids must be kept intact for human-to-human transmission to continue—mean no dN can happen here), you would find that in term of dS (unfortunately neither CAG, TAG nor TGG code for Arg any more), these codons are actually under neutral or slightly positive selection—not purifying selection. https://archive.ph/YXIf3 https://archive.ph/6B1Og https://archive.ph/dVoES Oops. The problematic sequence is the entire CTCCTCGGCGGGCACGTAG sequence, due to optimal binding with ZAP. ZAP binding is also the reason why double CGG-CGG Arg codons are even less likely than just the CGG-CGG motif itself. https://archive.ph/CFNcS https://archive.ph/VdpwJ https://pubmed.ncbi.nlm.nih.gov/33067384/ Also, part of the reasons why CGG-CGG pairs are so rare in Coronaviruses is related to the Toll-like receptors (TLRs). These receptors bind CpG motifs on dsRNA https://www.rcsb.org/3d-view/3CIY/1 (see the CpG on the dsRNA contact site with the TLR3 protein) at high affinity and this mean that while individual CGG-CGG motifs in the mRNA of bats may not be strongly suppressed due to the fact that genomic mRNA are single-stranded, they are strongly suppressed on coronavirus genomes because they form double-stranded RNA during replication where CpG motifs and especially double CGG-CGG motifs are strongly bound to the TLR receptors as dsRNA, leading to strong immune activation and efficient viral clearing. This affect all coronaviruses and lead to a depletion of CGG Arg codons compared to their host genomes, where SARS-like coronaviruses are one of the most affected clade amongst coronaviruses. (In fact, Rhinolophus spp. have the lowest transcriptomic homology to the CTCCTCGGCGGGCACGTAG sequence—the third CpG motif that is responsible for the strong ZAP binding on the antisense strand of the motif is absent in their transcriptome. Also making recombination with Rhinolophus spp. mRNA unlikely. https://archive.ph/Nfu5p) One of the reason why SARS-CoV-2 Wuhan is so bad at reinfecting animals. https://archive.ph/qXMsd https://gab.com/Flavinkins/posts/109106790806751902 As the problem with CpG is a problem that is related to the immune system, where double stranded RNA is more affected than single stranded RNA, the codon choice and CGG-CGG pairs are specific to coronaviruses, and neither (identically) applies to nor is (strongly) related to the somatic transcriptome of Rhinolophus spp. bats. Not even the CTCCTCGGCGGG sequence was found in coronaviruses, or Nidoviruses, outside SARS-CoV-2. In fact, selection pressure against an FCS in wild sarbecoviruses is so strong that it does not exist even as minor fractions within samples taken from the wild. http://archive.ph/vUy8n