COVID-19 is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised animal reservoir. Due to this recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any homoplasies observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we develop a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a curated set of recurrent mutations identified within a dataset of 46,723 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent mutations currently in circulation appear to be evolutionary neutral and primarily induced by the human immune system via RNA editing, rather than being signatures of adaptation. At this stage we find no evidence for significantly more transmissible lineages of SARS-CoV-2 due to recurrent mutations.
This study appears to assess evidence for whether recurrent mutations are associated with transmissibility, which is being taken as a proxy for fitness(though technically not identical with it). I’d be happy to say transmissibility of viruses is a significant contribution to viral fitness, and thus it’d be one of those components you’d want to look into to find evidence for adaptation, but it’s not the only one.
So no, taking one (though major) component of viral fitness and then looking for evidence of it only in recurrent mutations won’t allow us to conclude much about whether the virus is adapting to the human population. Of course, the pandemic is ongoing, and analyzing and understanding all the data this will continue to produce and drawing grandiose conclusions from it is premature.
Let’s talk about it again in 5 years. Maybe it’ll have gone extinct to genetic entropy by then?
I repeat myself: No, taking one (though major) component of viral fitness and then looking for evidence of it only in recurrent mutations won’t allow us to conclude much about whether the virus is adapting to the human population. Of course, the pandemic is ongoing, and analyzing and understanding all the data this will continue to produce and drawing grandiose conclusions from it is premature.
I simply don’t know whether the viral fitness has changed so far, and I won’t claim to be able to conclude anything about that at this time.
The definition of fitness isn’t different for viruses, it’s still absolute or relative reproductive success.
Though viruses do of course have a peculiar lifestyle as a sort of parasite, so we have to make some decision over what scale of time and environment to consider the reproductive success of particular carriers.
If we compare the relative reproductive success of individual viral mutants within a single host, one mutant might reproduce faster than another mutant while inside this host, but if this comes at the cost of the ability to transmit to new hosts (and if it kills the host), then that mutant might ultimately cause it’s own extinction.
I think that’s why ultimately biologists have elected to consider a different perspective for viral fitness by taking transmissibility into account, and to include the host population as part of what constitutes the environment, rather than merely thinking of the virus environment as the internal physiology of a single host. But that does admittedly imply that what counts as a beneficial or deleterious mutation has to depend in part on how widely we consider the environment, and the timescales over which evolution occurs. It is technically possible that a mutation that is beneficial in the context of viral replication within a host, is deleterious from the perspective of host-to-host transmission.
That means when we are talking about viral fitness, we have to agree on what ecological context in which we are measuring the reproductive success of carriers.
I do not think it is controversial to say that some organisms have ultimately evolved into their own extinction, because they were driven into strongly specializing towards some obscure, transient ecological niche by natural selection.
I think it’s fair to conclude that one mutation (not a recurrent one) did increase viral fitness: the D614G mutation in the Spike protein. It increased transmissibility of the virus and the mutant form has since outcompeted the original. Other than that, I haven’t seen any evidence that any persisting mutations are having any effect on viral fitness.
You didn’t read the paper? They specifically refute that.
But then this is virulence? and now you’re confusing me again - a virus can become more transmissible and more lethal @Rumraket? I don’t even know what to say anymore guys. Laugh or cry idk.
No. Now that I’ve looked at that part, I’m unconvinced. Their point about the other mutations that accompany D614G is already out of date, thanks to this paper, which looked at D614G in isolation. I think the probability that an obviously functional mutation that increases rapidly in frequency is actually neutral is very small. That, coupled with the very careful work in the UK study to me makes it very likely that D614G increased viral fitness. The failure of a different method to detect selection doesn’t refute its presence – it just means they didn’t detect it.
With an answer like that I think @thoughtful can be forgiven for being rather confused.
If virus transmissibility goes up, that means the virus is more frequently transmitting successfully to new hosts. But if transmissiblity is a measure of viral fitness (and if more transmissions = increased fitness), and the virus becomes more lethal, and it’s increased lethality results in hosts taking measures to avoid carriers(or carriers simply die before being able to transmit to new hosts), this results in fewer successful transmissions, and hence by definition fitness increases can’t simultaneously result in increased mortality and transmissibility.
Sure. Why not? If a mutation dramatically increases the ability of the virus to replicate in the host, it might well transmit more readily and also kill more quickly, which might on net decrease fitness.
I was taking transmissibility to be a measure of the rate at which the virus is transmitted, independent of the length of time over which it transmits. If that’s not what’s meant, then my answer above is incorrect.
You don’t seem to have read the paper. They specifically didn’t, and that’s even in the text!
Here we conversely find that D614G does not associate with significantly increased viral transmission (median log10(RoHO) = 0, paired t test p = 0.28; Supplementary Data 4), in line with our results for all other tested recurrent mutations. Though clearly, different choices of methodology may lead to different conclusions.
That’s not a “refutation” in any way, particularly given their acknowledgement that I bolded.
Nor is this: These apparently contrasting results for D614G should be considered carefully. What is, however, indisputable is that D614G emerged early in the pandemic and is now found at high frequency globally, with 36,347 assemblies in our data set (77.8%) carrying the derived allele (Fig. 1a and Supplementary Data 3). However, D614G is also in linkage disequilibrium (LD) with three other derived mutations (nucleotide positions 241, 3037, and 14,408) that have experienced highly similar expansions, as 98.9% of accessions with D614G also carry these derived alleles (35,954/36,347). It should be noted that the D614G mutation displays only five independent emergences that qualify for inclusion in our analyses (fewer than the other three sites it is associated with). While this limits our power to detect a statistically significant association with transmissibility…
This is how real science works. Real scientists carefully qualify their conclusions. Please stop portraying science as a high-school debate. Millions of human lives are at stake.
Thank you. I see that. I’m not a scientist, but I suppose I should act like one on a science forum.
I’ve already said that’s why I care about this topic and why I care whether scientists are getting it right. I guess I was reading about that mutation before, without realizing until now it’s the same one we’re discussing.
I’ve changed my mind since then. I actually care about the science more now. There’s lots of ways God can change people’s mind about origins, but science can only be changed by scientists.
Then please, please, stop pretending that it’s some sort of high-school debate that is entirely rhetorical. In this case, you’re not even bothering with textual analysis any more–you’re just reading the title and quitting.
BTW, are you aware that journal editors often change titles in the production process?
In summary, our results do not point to any candidate recurrent mutation significantly increasing transmissibility of SARS-CoV-2 at this stage and confirm that the genomic diversity of the global SARS-CoV-2 population is currently still very limited.
That’s unfortunate.
If you continue trolling me by asking me the same certain questions over and over, eventually you’re going to be muted.
I’d rather have an actual conversation. I’d like to be treated as a non-scientist willing to learn who has only been at this a few months - because it’s the truth. Maybe you could pretend I don’t have that “YEC” label for a while?
