Drs. Sanford and Carter respond to PS Scientists

Taking >150,000 generations for flies since creation, using a per generation deleterious mutation rate of 1.2 yields >180,000 deleterious mutations in the current generation of drosophila. This is of course a naïve calculation, but it is in response to Sanford’s more naïve hypothesis, and serves as an order of magnitude constraint. Sanford has not provided any rigorous estimates for thresholds at which catastrophe takes place, nor has he detailed how that would happen at the physiological level. Why are viruses, and flies, still with us, given that even with the outlandish timeframes of YEC, these species and many more should be long extinct were GE true?

Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila

…the divergence between taxa at neutrally evolving sites in the genome is proportional to the per nucleotide mutation rate, u, and this can be used to date speciation events by assuming a molecular clock. The overall rate of occurrence of deleterious mutations in the genome each generation ( U ) appears in theories of nucleotide divergence and polymorphism, the evolution of sex and recombination, and the evolutionary consequences of inbreeding…
Here we directly estimate u in Drosophila melanogaster by scanning 20 million bases of DNA from three sets of mutation accumulation lines by using denaturing high-performance liquid chromatography. From 37 mutation events that we detected, we obtained a mean estimate for u of 8.4 × 10-9 per generation. …By multiplying u by an estimate of the fraction of mutations that are deleterious in natural populations of Drosophila, we estimate that U is 1.2 per diploid genome.

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Note that the coefficient doesn’t depend on Ne, which was my point.

Yes, of course. Not what I was disagreeing about, which was the claim that s depends on Ne (among other variables).

Yes, but you seem to be misunderstanding my point. I’m not sure why.

This isn’t actually true. What’s required is that mutations cumulatively reduce the individual’s absolute fitness below replacement level. The population gets smaller and smaller until it’s extinct.

No, there is no model under which that’s true unless there’s a sizeable variance in the number of these nearly neutral mutations in the population. If the entire population’s absolute fitness is decreasing at about the same rate, no selection happens.

That’s not true. It’s only necessary that the sum of all the tiny little negative selection coefficients is large and that the differences in that sum among individuals is small.

You seem to be arguing for some kind of threshold selection, i.e. the straw that breaks the camel’s back. That seems like a very unrealistic model.

You still don’t seem to understand the GE model, and I don’t understand why. @glipsnort, can you help here?

Is the evolutionary force acting on the variant contingent upon s and Ne or not? If this is not your argument, then my apologies.

I am contending that the existence of nearly neutral variants is not sufficient for the GE hypothesis because GE requires that these variants kill the organism. Are you agreeing with this position or disagreeing?

I don’t think that makes sense. If the individual’s fitness is reduced, then we aren’t talking about nearly neutral variants anymore. We are speaking specifically about variants that are affecting the individual. These are not nearly neutral, by definition.

You would need to assume that individuals in the population are receiving the exact same mutations. That is absurd. If the entire population reaches a threshold where the number of nearly neutral mutations suddenly impacts fitness, the population does not simply die and will still explore the mutational search space i.e.–be privy to selection. You need to simultaneously bottle-neck the population and have large negative s in order for the population to die.

No, that’s not quite what I am saying. I am saying at some point s can be selected under some Ne. If the threshold for s is |0.001| and each nearly neutral is -0.0001, then once enough accumulate, NS turns on and can prune. You will never reach the threshold for extinction of -0.05 (or whatever). That threshold is hard-gapped by NS, s, and Ne.

GE requires that NS is turned off at all fitness determinants up to that threshold.

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I can see several possible sources of confusion.
First:

That’s not the case. GE works as long as the absolute fitness of the organism drops below 1.0 – no need for any killing.

Second, @chris_doesdna2018 seems to be assuming that all of the VSD mutations are segregating in the population, whereas if GE were correct, there would be a constant stream of such mutations fixing in the population, permanently reducing the absolute fitness.

Third, I think there’s a confusion about what the selection coefficient means in this case. If an individual allele has a selection coefficient of -0.05% in humans, it can efficiently be selected against because it has a slightly small probability of being passed on in every generation. But that is not the case when s represents the cumulative effect of thousands or millions of alleles. An individual’s fitness may be reduced by 0.05% because of the number of VSDs he or she happens to have, but there is no cumulative effect over subsequent generations for that particular set of VSDs. Or at least none that I can see.

@chris_doesdna2018, I suggest you deal with the model I posted upthread. As I said, it may be wrong, but if it is let’s figure out why it’s wrong.

  1. X and y are inversely proportional, and z is directly proportional:

    xy/z=K

  2. But K is a constant that doesn’t vary with X or Y or Z.

@chris_doesdna2018 is stating 1 and @John_Harshman is stating 2. What exactly is the argument?

5 posts were split to a new topic: Mendel’s Accountant

Does GE hypothesize the extinction of the organism on the basis of lowered fitness from the accumulation of VSDs? I’m curious why we would choose to ignore the predicted outcome of GE to placate the viability of neutral theory.

Do we want to generate a PRS for VSDs and map it to a liability threshold?

Mutations are constant. Segregation should be occurring given that they propagate via drift and will be treated as functionally neutral. Correct or am I missing something [edit: some LD/hitchhiker assumption]?

I’m treating s essentially as narrow-sense heritability i.e.–an additive model. It’s a simplistic assumption, either the coefficients add to modify the risk of fitness decline or they don’t. In either event, GE requires an extinction threshold for s that is crossed before purifying selection can take place. Maybe I’m not quite understanding the set of premises that obviate this issue. If the two thresholds are the same, then we would never be able to observe a patently deleterious variant–as it would kill the population.

I’m saying when:

|s| << 1/(2Ne)

then the variant attached to |s| gets to act neutral and is subjected to drift over NS. The on/off switch for NS is then proportional in magnitude to s and inversely proportional to 2Ne. There is almost certainly a better way for me to word this.

It hypothesizes the extinction of the species on the basis of lowered fitness from accumulated VSDs.

I don’t know what that means.

I can’t think of a reason for doing so, but if you can, please explain it.

You seem to be missing that mutations occur, segregate, and then fix. VSDs that fix lower the absolute fitness of the population and cannot be selected against. This progress is (under the hypothesis) progressive. I cannot tell from your response whether you understand that or not.

I’m afraid this is too vague for me to understand. Could you either respond to the model I proposed or offer your own mathematical model of the evolution of fitness in humans assuming, say, 50 new VSDs per birth?

Not sure what you mean by “evolutionary force”. Whether drift dominates selection depends on s and Ne. My point, once more, is that s doesn’t depend on Ne.

Disagreeing. GE doesn’t require that variants, or a combination of variants, kill the organism. It requires that variants reduce the population average absolute fitness below 1 recruitment per individual per generation. What’s required in order for selection not to prevent that is that the variance in absolute fitness resulting from nearly neutral alleles is low.

You are confusing absolute fitness with relative fitness. Natural selection acts on relative fitness, but GE is a claim about absolute fitness. You are also confusing individual mutations with an accumulation of mutations, each of negligible effect. The individual variants, if by that you refer to alleles, are nearly neutral. The aggregate of thousands of these alleles would not be neutral except that there is not sufficient variance in the number of them among individuals in the population for there to be differential reproductive success.

No, that’s not true. Not the exact same mutations. A number of these mutations achieve fixation in the population each generation equal to the mutation rate, and the number in a given individual’s genome, mostly inherited from parents, is not significantly different among individuals. The idea is that it takes a difference in number of thousands in order for selection to work.

You understand that this is not a threshold, right? Selection gradually reduces the probability of fixation below the neutral level as Nes becomes more negative. There is no magic point at which selection kicks in. And you still don’t seem to grasp that the variance in the number of nearly neutral alleles much be large in order for selection to operate well enough.

Not clear what you mean there, but I think it’s probably wrong.

Yes, if by the organism you refer to the species.

I don’t know what you mean by that. Who’s ignoring the predicted outcome? Who’s placating anything?

If that’s what you’re saying, in what way are you disagreeing with me? I would say that there is no “on/off switch”, just a fuzzy region in which fixation begins to be at less than the neutral rate.

Hi all, first time poster here: just wanted to raise a key point (apologies if this has been mentioned already).

Genetic entropy implicitly assumes that “perfect genomes” are a thing. If perfection is too biblical for you, then “correct genome” will also suffice. Basically, the idea is that there is a “correct” gene sequence for any given gene, and all mutations serve to degrade that archetypal sequence to some extent. And this is incorrect.
A lot of the (otherwise excellent) arguments I’m seeing here seem to be addressing the ‘degradation’ (or not) caused by mutation: the idea that ‘very slightly deleterious mutations’ can accumulate. You can argue that this accumulation is selectable against, but even to suggest accumulation occurs is, at root, a false premise: VSDMs are not accumulating, because ‘perfect starter genomes’ were never a thing, and cannot ever BE a thing. VSDMs are a phenomenon that has existed since the first primitive genomes arose. The starting point has always been “just barely viable”, and from there selection can only lead to either “better”, or “non-viable”. Only one of these outcomes persists.
We are, essentially, built exclusively from the least deleterious VSDMs, filtered through the prism of billions of years.

To even entertain the idea that life began at the “top” and iterated down is to fall into the creationist premise, and this premise is obviously false (I challenge PDP or Sanford to state the perfect height, eye colour, metabolic rate, or skin tone for humans). If instead one starts at the bottom and iterates up, one arrives at the exact same equilibrium point (i.e. where we are now), but one also now has an adequately robust framework to explain how we got here, and a framework within which to place all essentially non-selectable mutations. Very slightly deleterious mutations don’t accumulate…because they’re essentially replacing other very slightly deleterious mutations. Life did not start perfect, and life will never reach perfection (even if such perfection could be defined), it will always iterate to being as good as it can afford, and as crap as it can tolerate.

TL:DR, whenever you consider the sequence for any given gene, don’t fall into the trap of assuming that the canonical sequence is the “best”, and that all mutations mostly either degrade this or leave it unchanged. Life iterates to genes that are “crap but good enough”, and a corollary of this is that such sequences are robust to mutations. Perfection is easy to ruin, but robust mediocrity holds up far, far better.

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This smacks of the writing of a person who hasn’t yet bothered to read the joint article this post concerns. Or, for that matter, much of any of the rest of the dialogue here up to this point.

In which @Sweary_Biochemist’s point has been made repeatedly and been evaded repeatedly.

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2 posts were split to a new topic: Complaints about doctorates in thread titles

That’s fine, Paul. We’ve been here before.
Perfect genomes are a creationist requirement, and the challenge remains.
Provide

  1. the perfect height of a human
  2. the perfect eye colour
  3. the perfect metabolic rate
  4. the perfect skin tone
    I’ll accept an answer to any of these, provided you can give a convincing justification. If your answer to ANY of them is “if depends”, then…welcome to the reality of population genetics.
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Simply read the article, or read Dr Sanford’s book. See if his argument depends upon our knowing any of these things.

This is your description of GE you published in 2019.

Called genetic entropy, it is driving humanity—and all higher organisms—to the point of extinction (barring divine intervention, of course). In fact, this process, which operates more rapidly in ‘higher’ organisms means that the human species could only be several thousand years old; certainly not hundreds of thousands of years, or we would have already become extinct.*

*This topic is not widely known, but it’s very powerful support for biblical creation. Simply put, genetic entropy means that the information content in the genome (all of our genes) is progressively declining, due to the accumulation of mutations, generation after generation.

Creation Magazine 2019 Vol 41

Are you still going to pretend GE has no connection to your YEC claims or is not based on your YEC anti-science beliefs? Still going to ignore all the evidence humans and other extant species have been around for a heck of lot longer than 6000 years?

Please explain how you determined the information content in the genome is progressively declining. How did you measure the information content so you can tell if mutations make the content increase, decline, or stay the same?

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GE hypothesizes death–neutral theory allowing for VSD propagation under specific circumstances does not allow GE to “work.”

We want to know how many VSDs of what effect size will result in the death of the organism.

You seem to be missing that mutations occur, segregate, and then fix.

Right and the probability of VSDs occurring and reaching fixation and cumulatively having enough VSDs to phenotypically lower fitness is astronomical. Never mind lowering fitness from phenotypically imperceptible to catastrophic extinction avoiding selection the whole way. It’s not clear how one bridges the gap between selection coefficients becoming phenotypically perceptible to natural selection and the reduction of fitness causing extinction.

Something like:

(1/2Ne * P(VSDi))^n

where P(VSDi) = P(VSDi coding) + P(VSDi noncoding)
and i = specific probability of variant type
and n = number of cumulative VSDs that must occur and reach fixation and sum to a fitness commensurate with extinction.

It also assumes that all of humankind is a single mating population–completely bogus.

It’s not clear how you want to measure absolute fitness–especially in the context of a finite population whose variants are under the control of drift and whose variants do not produce phenotypes.

How are the fitness effects of each VSD accumulating? Do we add them? Do they interact? Are they synergistic etc.

“Force” as in a mechanism of allele frequency change. In this case, the trade off between drift and selection.

How should we measure W with variants that don’t produce phenotypes and are under the control of drift in a finite population?

Right–and so how do we walk from a 20 million base pair difference on average in humans, with inordinately high numbers of private SVs, to everyone has the same set of VSDs?

I’m not sure that I am :slight_smile:

There is no such thing in created humanity with front-loaded variation. I’m not aware if this is mentioned in the book, but I couldn’t help but comment to reduce confusion.

Well, of course we can’t. Why? There must be some distribution of small departures from neutrality even if we don’t know what it is. If that distribution is biased toward negative s, as GE must assume, then neutral fixations will also be so biased, and absolute fitness will decline.

There is no need for everyone to have the same set, just approximately the same number.

It seems that this is the one question that @PDPrice, Sanford and Carter and so on need to answer.

Before you can claim that the information content in the genome is progressively declining, and certainly before you can put a time limit on how long it could last, you MUST explain how the information content in the genome is measured.

Basically, until and unless we get some equations to work with, everything else is just waffle.

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