Slack / Private Message Drop — page 1000

[Andrew Rambaut] Would you pick CGG for example? Would you consider what codon to use for an R or just pick one arbitrarily. [2021-09-21 08:21:23] [Kristian Andersen] CGG would be an unusual choice IMO - not a 'optimized' R and sorta middle-of-the-pack as it comes to usage in human genomes. Very rare, of course, in viruses because it's a CpG. [2021-09-21 08:24:03] [Andrew Rambaut] And you have 6 codons to chose from. [2021-09-21 08:25:24] [Kristian Andersen] Correct. Key here too is that if you were to 'optimize' the FCS sequence (as is commonly done for these types of experiments) you would _not_ end up with the FCS sequence we see, including the CGG codons. But again, it doesn't really tell us much. [2021-09-21 08:26:15] [Kristian Andersen] What I think we have to look _very_ closely at are all the specific sites they talk about in the grant and then compare across our alignments - is SC2 unique in those positions compared to, say, the BANAL viruses? Does it flip back to SARS1 at some of these positions, etc. [2021-09-21 08:26:48] [Andrew Rambaut] Yup. [2021-09-21 08:27:39] [Kristian Andersen] I'll get some of this started later today - it's important to get the insights irrespective of what it's going to end up showing. [2021-09-21 08:28:55] [Andrew Rambaut] Would there be any reason to pick the SARS2 backbone for doing these? Assuming they had the genome sequence way back at the start? [2021-09-21 08:30:30] [Kristian Andersen] Well, in the grant they specifically talk about *new* viruses - so a SC2 precursor could have been one of those "low risk" viruses they talk about and then they started fiddling with it. [2021-09-21 08:34:27] [Andrew Rambaut] They would have selected it from candidates by genome sequencing it. I guess they would have seen an ACE-2 binding RBD and thought that is the one to try an FCS in? [2021-09-21 08:37:08] [Andrew Rambaut] Or they just were selecting viruses by seeing if they could get any to culture and then worry about genome sequencing? [2021-09-21 08:48:58] [Kristian Andersen] The former - which is the approach they describe in the grant.