[FRIAM] whackadoodles go mainstream!

[David Eric Smith]

Not my area of expertise, though for about the past year I have spent some time learning about proteins, so I am not as completely lost as I would have been before that.

The number of mechanisms that jointly get termed “evolution” in a complicated, mosaic, multi-host virus like this makes inference a many-dimensional problem.

Putting aside Marcus’s information on HLA variability, because I have not yet made the time to read it (though I hope to), just looking at the viral spike protein genes in the Nature letter to the editor, there seem to be at least two qualitatively different things going on.  The six mutated positions in the receptor binding domain are interpreted by the letter’s authors as plausible convergent mutations.  Since a lot of protein evolution seems to get locked in by structural or self-assembly constraints at many places, the number of labile positions on shorter timescales is some smaller number than the 20^211 that Marcus notes as an upper bound for brute force search (but again that is in the context of leukocytes, whereas these six mutations involve binding affinity to ACE2).  But when we see two solutions that seem to be in completely different basins of attraction in humans, as SARS-CoV and SARS-CoV-2 appear to be, there looks to be a big valley of non-viability between them, with very low probability to have all mutations occur conjointly to cross it.  I think people believe that between bats, cats et al., and now I guess pangolins (and I think I saw something about snakes from one letter that went around from an early researcher), there is an enormous reservoir of different strains, with a quite large diversity of ACE-type host proteins.  So we would be looking for island-hopping routes that make the SARS-COV and SARS-CoV-2 solutions mutually intelligible.  So the analysis of protein change mechanisms gets put into a larger context of ecological analysis of species contacts, which is probably as badly under-sampled as the viral diversity is.

The foregoing is independent of this “furin cleavage site”, and some special proline in a turn that facilitates attachment of surface amino-sugar chains.  This article suggests that such features are under selection from either or both of infectivity based on how the proteins are translated, and immunosurveillance.  Both of those will involve translational and immune proteins that vary significantly from one host to another.  (I assume this is where HLA variability becomes central to this story.). There was an article in NYT a week or two ago by James Gorman on why bats seem to be a reservoir for “so many viruses”
https://www.nytimes.com/2020/01/28/science/bats-coronavirus-Wuhan.html <https://www.nytimes.com/2020/01/28/science/bats-coronavirus-Wuhan.html>
(I don’t actually know whether they carry uncommonly more, per bat species, than other groups do per-species, since we often don’t know about things until they interest us enough to do a thorough survey, but if Gorman is writing with knowledge, that claim might be okay.). Certainly, there are an awfully large number of bats species, considering that they are just one little branch of insectivores.  If there is something different about bat immune systems, which pairs in an important way with the genome evolutionary position of coronaviruses, that would seem to be the first place to look for immune selection, as context for later asking about what is different in people.  The interesting thing is that these cleavage sites have not been found in other beta-lineage coronaviruses.  (He doesn’t say where they have been found, though that shouldn’t be a hard dig to get to.). The suggestion is that the CoV-2 strain is a mosaic that is mostly beta-coronavirus with something else.  The question is then, what else looks closest, where do the two occur together; what are the mechanisms for combining them.  Now we are in an epidemiology/ecology question.  

Inferring a chain of origin with all these factors in play looks challenging to me.  

Eric


> On Apr 21, 2020, at 8:35 AM, uǝlƃ ☣ <gepropella at gmail.com> wrote:
> 
> It's unclear to me whether we'd expect the virus to evolve faster or slower, depending on where it "originated". It seems to me that if it first appeared in a species that was dissimilar, then when it finally landed in a more optimal host type, it would evolve quickly (at least in non-critical regions) to thrive in that host type. On the other hand, if it lands in an almost already optimal host type, then it shouldn't evolve much at all. And only if it's under some sort of pressure to evolve (e.g. the immune system) would it do so quickly.
> 
> What *would* you people who can read all this stuff *expect* to happen?
> 
> On 4/20/20 3:57 PM, Marcus Daniels wrote:
>> As a ballpark the receptor binding domain is 211 residues, so 20^211, however only a small part of it seems to be actively evolving. [1]  (see Table 1)
>> 
>> https://www.biorxiv.org/content/10.1101/2020.03.10.986398v1
>> 
>> *From: *Friam <friam-bounces at redfish.com> on behalf of David Eric Smith <desmith at santafe.edu>
>> *Reply-To: *The Friday Morning Applied Complexity Coffee Group <friam at redfish.com>
>> *Date: *Monday, April 20, 2020 at 3:49 PM
>> *To: *The Friday Morning Applied Complexity Coffee Group <friam at redfish.com>
>> *Subject: *Re: [FRIAM] whackadoodles go mainstream!
>> 
>>    https://www.nature.com/articles/s41591-020-0820-9?fbclid=IwAR1vyx1SqreXoeVgFVKBIayEWGOgZn5IbXmx3-V4nsrWiIlrYvYHQW2TuLA 
>> 
>> There is discussion in here about the kind of mosaic it is, and the nearest identified variants for different parts.  I find this interesting as a question in evolutionary dynamics of either convergence or recombination.  The question of how “hard” an engineering problem it is to find non-local optimizers for various biding problems if you happen not to have templates in the same basin of attraction is an interesting question to me in methods of protein biochemistry.  The question of what level of sophistication we currently imagine is in use around the world is a potentially interesting question of sophistication versus availability of method, also practical if one works in threat defenses.
> 
> -- 
> ☣ uǝlƃ
> 
> .-. .- -. -.. --- -- -..-. -.. --- - ... -..-. .- -. -.. -..-. -.. .- ... .... . ...
> FRIAM Applied Complexity Group listserv
> Zoom Fridays 9:30a-12p Mtn GMT-6  bit.ly/virtualfriam
> unsubscribe http://redfish.com/mailman/listinfo/friam_redfish.com
> archives: http://friam.471366.n2.nabble.com/
> FRIAM-COMIC http://friam-comic.blogspot.com/ 

-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://redfish.com/pipermail/friam_redfish.com/attachments/20200421/0edb654c/attachment.html>