Drs. Sanford and Carter respond to PS Scientists

Unplanned changes that break a functional biological “machine” get weeded out by selection. Unplanned changes that improve a functional biological “machine” get rewarded by reproducing more and being fixed in the population. This is so obvious it should not need to be debated by intelligent people.

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Simple question: Will every genome in the population have approximately equal absolute fitness? Perhaps you could ask Carter and/or Sanford so we can be confident that the answer accurately reflects their model.

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I too, am skeptical of the idea that mutational load would be so evenly spread out in a large population, that there would be no basis for competitive selection. Is not sexual selection particularly suited for this type of ranking?

Every? No. In that case, there would be no selection at all. Some genomes have significantly worse fitness, such that natural selection will have a chance to work. Most, however, will be along a fairly level spectrum, because most mutations are of extremely small effect, and mutation rates don’t vary much by the individual–as I believe you have also confirmed. Most of the genetic differences will be far too insignificant to rise above the myriad of non-genetic factors at play in survival and reproduction. The princess and the nucleotide paradox comes into play, in other words. I would suspect that @glipsnort would be able to confirm that at least what I’ve said in this paragraph is entirely accurate.

Go ahead. Show me a quote in which Sanford says that purifying selection doesn’t exist.

What do you mean by “it”? Do you understand what “nearly neutral” means? The deleterious alleles Sanford is talking about (which I maintain he doesn’t think are the only deleterious alleles there are) do not individually cause extinction. Each of them reduces absolute fitness by a miniscule amount, and they increase in frequency (well, a small percentage of them do) by drift alone. Selection is unable to eliminate them. If you pile up great numbers of them (and we’re talking thousands or millions here) they have a strong effect on absolute fitness, but they have no effect on relative fitness if there is no significant variance in the number of such alleles among individuals. Thus selection can’t eliminate them and there is a gradual deterioration of absolute fitness in the population until we reach extinction.

No. But the variance is likely to be entirely in terms of the few alleles with significant deleterious effects, not the great number of nearly neutral alleles. Significantly deleterious alleles are irrelevant to the GE model. They are eliminated by selection, but that doesn’t change the distribution of nearly neutral alleles in the population.

Now of course GE doesn’t actually happen. But the reasons it doesn’t have nothing to do with what you seem to be supposing.

Sorry, but that’s been explained to you over and over, and you still don’t get it. The only mutations we can determine to be deleterious (or advantageous) are those with selection coefficients sufficiently large to be affected by selection. Nearly neutral mutations can’t be assumed to have the same distribution as those of large effect. And there are good reasons to suppose that most mutations are strictly neutral, or at least so nearly neutral that even in massive aggregate they have no significant effect on absolute fitness.

No. And that isn’t what GE is about. Again, it’s about the absolute fitness component produced by accumulated nearly neutral alleles. Significantly deleterious alleles are irrelevant to the model. They happen, they’re eliminated by selection, and the nearly neutral allele distribution is unaffected.

No. Why should that be?

That’s a non sequitur. This isn’t about mutations in individuals but about the distribution of nearly neutral alleles, most of them ancient, in the population.

I am not acquainted with this paradox. Do tell.

A post was merged into an existing topic: Correcting a Quote Mine on Deleterious Mutations

Because mating behavior is very discriminating to even the most trivial phenotypical differences between prospective partners, and can capture aggregate relative genetic health? I have not read any literature on this, but it seems workable to me. I am open to being schooled here.

Great, thank you.

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That’s not the claim.

If an allele or set of alleles has a detrimental, non-zero impact on relative fitness (i.e. the selection coefficient is actually negative, rather than literally zero), then by definition it is selected against. We should be able to agree on that.

Since we (should) agree on that, if these accumulated nearly neutral mutations, in total, within each genome, have a detrimental, non-zero impact on fitness, they will, as a set of mutations, be selected against, unless the relative fitness of every member of the population is so small the difference is unselectable .

Since that last caveat is completely unrealistic, selection can operate. Not efficiently, but it’s operating. And what happens when so many such mutations build up that a specific genotype becomes non-viable? That’s what I’m referring to with the “it” you asked about above - “nearly neutral” doesn’t describe something that’s imminently causing extinction. At this point, selection becomes very strong, right? This is what Sanford disputes. That even as these small-effect mutations cumulatively cause large effects , purifying selection still fails to operate, and the population ultimately goes extinct. And of course that’s just not what happens.

It seems like maybe what you’re disputing is that there would be sufficient differences in relative fitness?

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A post was merged into an existing topic: Correcting a Quote Mine on Deleterious Mutations

With this you are departing from what the experts in the field clearly state. It’s not just that strictly neutral mutations are rare–they are believed to be non-existent.

Here’s a link to the handout I created for my debate with Dr Ron Garret:

Note the citations for Premise 3.

It’s not a mere assumption, since most mutations are nearly neutral. Which means all our data on mutation accumulation are showing us, more than anything else, the effects of nearly neutral mutations. But ignoring that, just back up this statement. You’re claiming that the DFE for nearly neutrals is contrary to all the mutational data we possess. Why? Are you willing to grant that if the DFE for nearly neutrals is the same as, or similar to, the DFE for larger-sized mutations, then evolution is sunk?

It’s from Sanford’s book. Why don’t you read it? You want to debate against it, but you haven’t read it, so you don’t really know the full extent of what Sanford has to say in the first place. In a nutshell, it’s an analogy of the princess and the pea–a mythical princess is said to be able to feel a single pea underneath a huge stack of mattresses, and is so disturbed by it that she cannot sleep. This is like natural selection being able to “see” a single point mutation in a genome, and select it out. Or any nearly-neutral mutation at all.

This is not a regime for which I have good intuition, so I’m trying to develop some. Take heterozygosity as providing a crude estimate of the number of these very slightly deleterious alleles that any human is carrying. Human heterozygosity is ~0.1%, which yields 3,000,000 VSD alleles. Assume they’re Poisson-distributed, which gives 3,000,000 +/- 1700 (1 SD). Since we’re not dead (well, some of us aren’t), take the fitness effect of each VSD to be ~1/3000000. That would imply a fitness difference between someone with +1 SD of the deleterious allele load and someone with -1 SD of ~0.1%. (Larger if you think relative fitness will vary more than absolute fitness.) Is that selectable? I still don’t know. If it were a single variant, sure, but a single variant is perfectly heritable, so selection can act cumulatively over generations, while the number of VSD alleles is only weakly heritable.

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You don’t understand mating behavior. It tends to key onto a very few characters. While small differences in those few may be detectable, and there are hypotheses that some of those characters may be indicators of general health, the connection isn’t strong enough to support your claims. Further, you have to realize that the theory of this nearly neutral genetic load suggests that no individuals are significantly different, to the degree that there would be a basis for choice based even on signals of health. The whole population goes down together.

What is the claim? And whatever it is, please support it with a quote.

No. The whole point of nearly neutral theory is that given a small enough selection coefficient (or one sufficiently close to 1, if you think of it that way), and depending on population size, drift outweighs selection and the allele is effectively neutral. I’m afraid, despite whatever academic qualifications you have, you do not understand nearly neutral theory.

Once again, it isn’t the relative fitness per se that counts, it’s the relative fitness contribution of the set of nearly neutral alleles. Significantly deleterious individual mutations are eliminated by selection without affecting the distribution of nearly neutral alleles. You objection is not valid.

The species goes extinct, if all the genotypes are similarly burdened. As a matter of fact, the problem increases as the population size diminishes, because more deleterious mutations become invisible to selection.

No. It only becomes strong if there’s sufficient variance in the number of nearly neutral, deleterious alleles, enough to make a difference in relative fitness. Since we’re talking about thousands of alleles of insifificant individual effect, that variance seems to me quite unlikely.

Exactly. That’s the whole point here. But again, the relevant differences have to be within the set of nearly neutral alleles. There can be great differences in fitness resulting from mutations of significant effect, but that wouldn’t change the distribution of nearly neutral alleles. There would be no selection acting on them.

What experts, on the basis of what evidence? Previously, your only citation was to an unattributed claim in one review article. I have reason to suppose that your document does better than that.

No, it doesn’t. You are very confused on this. The data on the distribution of selective coefficients is based entirely on the minority of mutations with significant, observable effects on fitness. How could it be otherwise?

No. You would have to ignore all the data showing that evolution actually happens in order to come to that conclusion. At most, our theories of how evolution works would need to change. You might even propose that God periodically launders genomes. But you can’t just assume the facts you need.

It’s apparent enough that the book is nonsense, just from what has been shown here.

This comes dangerously close to denying that selection happens, as others have accused you of. Whether the princess feels the pea depends on the size of the pea, doesn’t it?

Don’t suppose. Just open the doc and read the citations. That’s the point. Don’t keep engaging with me if you’re going to simply ignore my answers anyway.

When we look at mutation accumulation over time, we are seeing an overall picture of what mutations, in general, tend to do. That is, for example, what Carter and Sanford looked at in the history of H1N1 over time. This is also a good picture of nearly neutral mutations, since most mutations are nearly neutral.

In other words, evolution is unfalsifiable. Since any disproof can simply be waved away on account of “all the data”.

If evolution doesn’t work, then it didn’t happen. Period. No matter what you think you see in the fossil record (you’re actually misinterpreting it). There is no proposed mechanism for evolution besides mutations, NS and drift. Yet these don’t produce the desired result.

That is, in essence, what is being proposed by Steele et al.

Don’t be willingly ignorant. Read it for yourself, since you clearly care enough about the subject to spend time debating it.

The vast majority of peas are extremely small. Which means the princess cannot feel most of them.

“… particularly
for multicellular organisms … most mutations, even if they are deleterious, have
such small effects that one cannot measure their fitness
consequences.”
Eyre-Walker, A., and Keightley P.D., The distribution of fitness effects of new mutations, Nat. Rev. Genet. 8(8):610–8, 2007.
The distribution of fitness effects of new mutations | Nature Reviews Genetics.

I can only see the first page, as the rest fail to load. But that first page consists of unsupported statements, at least two of which are clearly quote-mined.

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This is silly. What is the equation for s?

(It also appears, based on an above comment, that you haven’t read Sanford’s book in which he presents his argument. I would hope that one would read the thing they are characterizing before engaging in a discussion over it.)

I don’t know why that would be. It’s working fine for me, and nobody else has reported having this issue. Here’s the text:

Premise 3:
There are no ‘strictly neutral’ mutations, but there exists a class of
mutations called ‘effectively neutral’ (a.k.a. nearly neutral) whose effects
are too subtle to be ‘seen’ by the process of natural selection, and are
therefore free to accumulate in populations over time.

  1. “… it seems unlikely that any mutation is truly neutral in the sense that it has no effect on
    fitness [!]. All mutations must have some effect, even if that effect is vanishingly small.
    However, there is a class of mutations that we can term effectively neutral. These are
    mutations for which Nes is much less than 1, the fate of which is largely determined by
    random genetic drift. As such, the definition of neutrality is operational rather than
    functional; it depends on whether natural selection is effective [!] on the mutation in the
    population or the genomic context in which it segregates, not solely on the effect of the
    mutation on fitness.”
    Eyre-Walker, A., and Keightley P.D., The distribution of fitness effects of new
    mutations, Nat. Rev. Genet. 8(8):610–8, 2007.
    doi.org/10.1038/nrg2146

**Note my added exclamations: clearly, the idea of ‘fitness’ is actually
divorced from natural selection/selectability in population genetics. This is
the unspoken division of absolute vs. reproductive fitness!

  1. “Note that even if the frequency of strictly neutral mutations (for which s’ = 0) is zero in
    the present model, a large fraction of mutations can be effectively
    neutral …”
    “Under the present model, effectively neutral, but, in fact, very slightly deleterious
    mutants [!] accumulate continuously in every species…the rate of loss of fitness per
    generation may amount to 10-7 per generation. Whether such a small rate of
    deterioration in fitness constitutes a threat to the survival and welfare of the species (not
    to the individual) is a moot point, but this will easily be taken care of by adaptive gene
    substitutions that must occur from time to time (say once every few hundred
    generations).”
    Kimura, M., Model of effectively neutral mutations in which selective constraint is
    incorporated, Proc. Natl. Acad. Sci. USA 76(7):3440–3444, 1979.
    Again, as you can see, according to Kimura a mutation can be deleterious
    and ‘effectively neutral’ at the same time. This is because the mutation is
    affecting absolute fitness without affecting reproductive fitness. Kimura
    also believed that ‘strictly neutral’ mutations were so rare as to ignore them
    completely in his model.

Pardon?

We’re disagreeing over whether a thing could be selected or not. What’s the equation for the coefficient of selection?

I’m clearly not a population geneticist, and I successfully avoided taking any courses in population genetics during my entire graduate career, but if I recall it’s the expected change in frequency from one generation to the next. I don’t see why this matters, unless you’re trying to assert your authority. Are you a population geneticist? If so, it’s odd that you don’t understand nearly neutral evolution.

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