Coronavirus variants contradict the predictions of genetic entropy proponents

[SlightlyOddGuy (Matt)]

I did have one question maybe some of you could answer. Let me start with some background first.

Back when this topic was last going around on here, I asked @PDPrice how they measured the effect of VSDMs, and his answer was something along the lines of: we can’t, because they’re so small. Which… okay, seems kinda sus to hang your GE hat on that, but if they’re too small to measure, that’s just the way it is.

But he continued to respond, saying that it’s not a big deal that we can’t directly measure those VSDM effects, because actual beneficial mutations are so incredibly rare that VSDMs inevitably overcome whatever benefit they provide. This also seems kinda sus to me as well, since the fitness cost could range from (0, limit of measurement].

As I understand it, mainstream scientists and YEC scientists sharply differ on the frequency of beneficial mutations. But the fact that we’re talking VSDMs vs, idk, “regular” mutations implies we can actual measure the “regular” ones. So my question would be this (and Paul, feel free to throw in your two cents here):

1. What method do YECs use to measure the fitness effects and frequency of mutations? I’m just wondering where this difference comes from and how it’s backed up by some real world data. My exposure so far has been either something from Mendel’s Accountant or “measurement by analogy”. What have I missed?

Thanks, everyone.

[Michael_Okoko]

@Giltil

The hypothesis is that these viruses can exist in a somewhat dormant state in their natural reservoirs.

Clarify what you mean by “dormant state” so that we can clearly test your hypothesis using available data?

[RonSewell (RonS)]

@Chris_Falter

If the answer is yes, let’s ask another question: How would there be any influenza or coronavirus strains in existence today if the strains that existed in 2000 BCE had to inevitably, per the hypothesis of genetic entropy, go into decline and demise?

@Giltil

The hypothesis is that these viruses can exist in a somewhat dormant state in their natural reservoirs.

This glaring contradiction to GE for the influenza case has been recently discussed in the thread @Giltil initiated here:

Influenza may be in evolutionary stasis in its natural reservoir after all

But of course, the issue goes beyond just influenza and extends to all viruses everywhere, including coronavirus. Viruses by definition require the cellular machinery of mortal hosts to replicate, a process entirely exposed to GE; and yet through history until the present, they have been a persistent and pervasive presence. That we are supposed to accept that each and every pathogenic virus on the planet has been preserved and hiding out, biding their time as in some super villain’s lair, for thousands of years, is not just wrong but is outlandish.

[glipsnort (Steve Schaffner)]

@RonSewell

That we are supposed to accept that each and every pathogenic virus on the planet has been preserved and hiding out, biding their time as in some super villain’s lair, for thousands of years, is not just wrong but is outlandish.

It’s wrong and easily testable. Just measure the substitution rate of viruses in their reservoirs, either directly or by measuring the divergence between spillover outbreaks in humans. The viruses I’m familiar with – rabies, Lassa, Ebola – all have unremarkable substitution rates in their reservoirs. This is a biologically absurd hypothesis that is contradicted by multiple data sources, and that was only introduced to rescue another biologically absurd hypothesis that has no evidence for it and considerable evidence against it.

[thoughtful (Valerie (non-scientist))]

sigh. I was reminded why I decided not to respond to GE threads. Too many replies to me and the conversation always covers the same ground already addressed but the variants are interesting and relevant.

Anyway, I might try to respond to some replies, just not tonight. I had to work and too many things to do.

However, I wanted to share the Wired article I read tonight, because I thought it was, by far, the most informative popular article I’ve read so far on the all the variants.

Worrisome New Coronavirus Strains Are Emerging. Why Now?

@glipsnort

all have unremarkable substitution rates in their reservoirs

Meaning - they have expected substitution rates or low ones?
When you refer to natural reservoirs are you usually referring to an animal host? What if it’s just out in the environment?

[T_aquaticus]

@Giltil

Therefore, it is not at all surprising that at the beginning of an outbreak, a virus can adapt rapidly to its new environment through a serie of beneficial mutations until it reach a natural optimum, at which stage the relentless accumulation of slightly deleterious mutations will begin to slowly take effect.

These viruses had already been reproducing in their natural reservoirs for at least millennia before the outbreak. According to GE, they shouldn’t even exist at this point.

[T_aquaticus]

@Giltil

The hypothesis is that these viruses can exist in a somewhat dormant state in their natural reservoirs.

This is disproven by the actual life cycle of RNA viruses. They must continually reproduce.

[Michael_Okoko]

@Giltil

The hypothesis is that these viruses can exist in a somewhat dormant state in their natural reservoirs.

Another way we can test this hypothesis is to examine viral replication in human reservoirs. Humans are natural reservoirs to viruses like the measles and smallpox viruses. AFAIK, these viruses are far from dormant, falsifying this hypothesis.

[Giltil (Gilbert Thill)]

@Rumraket

But doesn’t that imply that since they begin being rather likely, that there must be a very large number of them. Otherwise, why are they likely to begin with? What is it that made the D to G mutation at position 614 in the spike protein likely to begin with, but some other substitution in a protein much later in the pandemic is very unlikely?

The mutation rate of RNA viruses such as Influenza is so high that within the viral swarm present in a single infected person, every position of the viral genome is likely to be occupied by the 4 based. So it is not surprising at all that an adaptive change such as the D to G mutation at position 614 in the spike protein of sars-cov2 can be found and selected very quickly during an outbreak.

[Giltil (Gilbert Thill)]

@glipsnort

It’s wrong and easily testable . Just measure the substitution rate of viruses in their reservoirs, either directly or by measuring the divergence between spillover outbreaks in humans

To perform this type of analysis, you would first have to be sure that you know all the possible natural reservoirs of the virus you are studying, which in most instances is probably very far to be the case. The virosphere is a gigantic continent that we have barely begun to explore.

[Chris_Falter]

@thoughtful

What if it’s just out in the environment?

So I did a quick Google search, and here’s what I found: Viruses degrade at various rates, depending on the virus and the conditions.

The flu virus can stay active on some surfaces for up to 48 hours, according to the CDC.

The Ebola virus can survive on doorknobs and countertops for several hours.

The norovirus can survive up to four weeks on surfaces, said Charles Gerba, a professor of microbiology and immunology at The University of Arizona.

But years or even months? Nah.

Best,
Chris

[Giltil (Gilbert Thill)]

@RonSewell

That we are supposed to accept that each and every pathogenic virus on the planet has been preserved and hiding out, biding their time as in some super villain’s lair, for thousands of years, is not just wrong but is outlandish.

First, you don’t know if it is wrong. Saying otherwise would be an example of what Behe called « the pretence of knowledge ».
Second, it may look outlandish, but the history of science is rich in hypotheses which at first appeared outlandish but which finally turned out to be true.

[Giltil (Gilbert Thill)]

@glipsnort

This is a biologically absurd hypothesis that is contradicted by multiple data sources, and that was only introduced to rescue another biologically absurd hypothesis that has no evidence for it and considerable evidence against it.

There are historical evidence of GE in RNA viruses. Sanford & al have a paragraph on this in their paper « Information Loss: Potential for Accelerating Natural Genetic Attenuation of RNA Viruses ». Here it is:
https://pdfs.semanticscholar.org/32b3/0fda9aaacbff4da7bb04b30736469fb5197c.pdf?_ga=2.188461995.2059449984.1611856430-42908154.1611856430

[Rumraket (Mikkel R.)]

@Giltil

The mutation rate of RNA viruses such as Influenza is so high that within the viral swarm present in a single infected person, every position of the viral genome is likely to be occupied by the 4 based. So it is not surprising at all that an adaptive change such as the D to G mutation at position 614 in the spike protein of sars-cov2 can be found and selected very quickly during an outbreak.

That does make sense, thanks. What doesn’t make sense, biochemically speaking, is then the idea that the virus can somehow mutate itself to extinction while under selection. If it’s fitness starts declining due to VSD mutations in the spike protein (for example), then what’s to prevent another mutation of large effect from restoring the binding ability of the spike protein? It seems to me there is no protein in the virus’s genome that could actually mutationally decay in the manner GE requires. The rust analogy fails to capture how molecular biology actually functions.

[Rumraket (Mikkel R.)]

@T_aquaticus

These viruses had already been reproducing in their natural reservoirs for at least millennia before the outbreak. According to GE, they shouldn’t even exist at this point.

But you can’t say that as there’s no actual GE model that predicts a time of extinction for… anything.

[dsterncardinale]

@Giltil

So none of what’s going on currently with sars-cov2 contradicts the predictions of GE proponents.

What, as specifically as possible, would contradict GE?

Would a completely new function without any loss of any preexisting functions do it? Would completely neutral changes with precisely zero effects on fitness or any biochemical processes do it? if GE is actually a testable hypothesis, there must be some set of observations that are incompatible. What would those be?

[Rumraket (Mikkel R.)]

Queue the straw-man of evolution that isn’t actually the theory of evolution. GE would be contradicted if every time we did an evolution experiment, regardless of the environmental or ecological conditions tested, the population being tested would under all circumstances, always and without exception, simultaneously increase in fitness, increase in the number of both phenotypic, biophysical, and biochemical functions, and all imaginable measures of information. That, only that, and nothing less than that, would constitute evidence against GE.

[Giltil (Gilbert Thill)]

@Chris_Falter

@thoughtful

What if it’s just out in the environment?

So I did a quick Google search, and here’s what I found: Viruses degrade at various rates, depending on the virus and the conditions.

The flu virus can stay active on some surfaces for up to 48 hours, according to the CDC.

The Ebola virus can survive on doorknobs and countertops for several hours.

The norovirus can survive up to four weeks on surfaces, said Charles Gerba, a professor of microbiology and immunology at The University of Arizona.

But years or even months? Nah.

Not only months or even years, but thousands of years!
For example, see this:

Persistence of Avian Influenza Viruses in Various Artificially Frozen...

Or this post by @RonSewell

Influenza may be in evolutionary stasis in its natural reservoir after all

I agree that the idea of abiotic preservation cannot be just summarily dismissed. Not specifically influenza, but here is a paper surveying findings relevant to idea that microbes might survive long periods of freezing: Future threat from the past The remarkable finding of an ancient virus: Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology And some popular level articles: BBC - There are Diseases Hidden in Ice SciAm - As Earth Warms, the Diseases That May Lie within Permafrost Become a Bigger Worry Vox - Melting permafrost in the Arctic is unlocking diseases The permafrost pandemic: could the melting Arctic release a deadly disease?

[RonSewell (RonS)]

@Giltil

First, you don’t know if it is wrong.

We know it is wrong because we know what is right. Natural reservoirs host hundreds of viral pathogens, and variants beyond counting. This did not happen overnight, but is the result of centuries and millennia host - virus interaction. Some natural reservoirs are wide ranging, such as water fowl, others are much more climate constricted and have very little overlap, such as bats.

@Giltil

the history of science is rich in hypotheses which at first appeared outlandish but which finally turned out to be true.

Some hypotheses have been counterintuitive, but ultimately supported by evidence. Sanford’s ideas in regards to epidemiology lack internal consistency and are disqualified by evidence which has already been known for decades, which is why virologists pay him so little attention.

Viral strains are superseded by subsequent strains not because GE drives them to extinction, whereupon they are replace by more archaic, unmutated strains. The opposite is the case. Either the host population adapts to the challenge, or as we see with the current pandemic, they are pushed aside by subsequent, positively mutated strains. Sanford has it backwards. Pandemics in both human and animal populations happen not because a virus is unmutated, but because it is mutated. This is the “arms race” model of pathogenic infection.

We find extensive history not just embedded in extent viruses, but their signature also in hosts.

Here, we show the highly polymorphic ACE2 in Chinese horseshoe bat populations. These ACE2 variants support SARS-CoV and SARSr-CoV infection but with different binding affinities to different spike proteins. The higher binding affinity of SARSr-CoV spike to human ACE2 suggests that these viruses have the capacity for spillover to humans. The positive selection of residues at the interface between ACE2 and SARSr-CoV spike protein suggests long-term and ongoing coevolutionary dynamics between them.

Evolutionary Arms Race between Virus and Host Drives Genetic Diversity in Bat Severe Acute Respiratory Syndrome-Related Coronavirus Spike Genes

Host genomes, however, offer an indirect way to detect ancient epidemics beyond the current temporal and physical limits. Arms races with pathogens have shaped the genomes of the hosts by driving a large number of adaptations at many genes, and these signals can be used to detect and further characterize ancient epidemics. Here, we detect the genomic footprints left by ancient viral epidemics that took place in the past approximately 50 000 years in the 26 human populations represented in the 1000 Genomes Project. By using the enrichment in signals of adaptation at approximately 4500 host loci that interact with specific types of viruses, we provide evidence that RNA viruses have driven a particularly large number of adaptive events across diverse human populations. These results suggest that different types of viruses may have exerted different selective pressures during human evolution.

Ancient RNA virus epidemics through the lens of recent adaptation in human genomes

Here we argue that the coevolutionary arms race between humans and their viral pathogens is one of the most important forces in human molecular evolution, past and present. With a focus on HIV-1 and other RNA viruses, we highlight recent developments in our understanding of the human innate and adaptive immune systems and how the selective pressures exerted by viruses have shaped the human genome. We also discuss how the antiviral function of cellular machinery like RNAi and APOBEC3G blur the lines between innate and adaptive immunity. The remarkable power of natural selection is revealed in each host-pathogen arms race examined.

Point, Counterpoint: The Evolution of Pathogenic Viruses and their Human Hosts

[RonSewell (RonS)]

@Giltil

The mutation rate of RNA viruses such as Influenza is so high that within the viral swarm present in a single infected person, every position of the viral genome is likely to be occupied by the 4 based.

I would be very interested in a reference that mutation runs to saturation in typical given host. If this is the case, how is it that we are able to track the phylogeny of viral spread, and identify strains at all, as each person to person spread would be from entirely randomized viruses. It cannot be selection, because we observe there are thousands of viable and neutral mutations possible.