May it? How, exactly?
I doubt it. Perhaps you would like to provide a link which will permit reading of the entire thread, and explain why you think so.
In his thread, G Monroe presents evidence that epigenome-associated mechanisms reduces the occurrence of mutations in functionally constrained regions of the genome, ie reduces mutation load. It seems to me that this phenomenon is to be factored in when discussing the mutation load argument.
If you read the full discussion, you will see that is well addressed. No one is claiming the mutation rate is uniform. No one is claiming that non-uniform randomness makes the mutational load go away. Any way you slice it, the mutational load is a strong indicator that much of the human genome is non-functional.
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My understanding of the mutation load argument is that there is a relationship between the mutation load and the fraction of the genome that can be functional, the higher the former, the lower the latter. So clearly if some mechanisms exist that reduce the mutation load, that will allow for a larger functional genome.
Why and how? If indeed all the genome is functional, which is the target of the argument, then the deleterious mutation rate estimated from known functional regions should apply, and genetic load is a problem.
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If some mechanism exists to reduce mutation load on functional regions, and that mechanism is only active on a small fraction of the genome, that’s evidence of a smaller functional genome.
You have not read your material very carefully.
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I think John and Crisp have already touched on what I was going to say. Your question presumes that some significant proportion of the genome is non-functional. That’s OK, but it’s not your usual position on this topic (IIRC).
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Another question is the magnitude of effect. Just how much is the rate of mutation reduced in the protected regions?
What I understand is that the arguments of genetic load and evolutionary conservation rule out that functional DNA is linked to a specific sequence, and therefore either most of the DNA is junk or most of it is functional but its function is not linked to a specific sequence, but what I tend to think is that most of it is junk because our genome is full of With defective Transposons and retrovirus, and these retrovirus are polymorphic. If they perform a function, we would find a difference in fitness between those who have defective retrovirus and those who do not have them. However, I cannot rule out the idea that they may be performing a specific function that we do not know.
Note : Yes, there are some transposons and retroviruses that have a function, but that does not mean that all transposons and retroviruses have a function in our genome .
If my understanding of the paper below is correct, the case for the mutation load argument (as it relates to the proportion of the functional genome) doesn’t hold, especially for mutations with small selection coefficient, which are precisely the type of mutations that worried Sanford most.
The basis of this argument is that the variance in fitness among individuals in a population is not likely to be high. But does this affect the mutational load argument, which doesn’t depend on selective differences among individuals but rather upon reduced absolute fitness below that needed to maintain a viable population? Serious question, since population genetics is largely outside my competence.
You can go ahead and try to make the connection to the thing you first posted, and the thing you’re now posting.
What is this evolutionary conservation argument and why would it rule out that functional DNA is linked to a specific sequence?
If your understanding is correct and the paper is correct.
Your understanding appears correct. The paper not so much.[1][2]
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They seem to assume that the number of deleterious mutations is independent of the fraction of the genome that is functional. This is not possible.
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The fitness values they use are relative, scaled to the mean fitness of the current population. This will hide any overall fitness increase or reduction
There are multiple comments that may need to be edited for corrections. I suggest a short pause so people can edit as needed before continuing discussion. I’ve turned on slow mode for three hours as a reminder.
Let me know if slow mode interferes with edits - that would be bad.
Sure, this is not possible. But as far as I can see, they don’t assume such thing. Where did you get this impression ?
In the paper referred to at 31 there is a passage (see below) that seems to contest the idea that the load is independent of the selection coefficient s. What do you think of it?
Remarks on the Haldane Load
Agrawal and Whitlock (2012) define the load as in (1), so that for them the load in the additive case is L=1−e−2nu, and make two comments about this formula. First, they state that the fact that this load formula is independent of s has led to a “misleading sentiment” among theoretical population geneticists who then feel that nothing need be known about the value of sor about ecological considerations in assessing loads. We agree, and believe that load calculations that ignore s are not realistic (see table 1) and have influenced population genetics theory for far too long. Second, they state that there is very little empirical evidence that Haldane’s (1957) load theory, based on the formula L=1−e−2nu, is even approximately correct. A likely reason for this lack of evidence is that Haldane’s theory, being based on this formula, is not empirically relevant to populations with parameters similar to those for humans.
In humans, nu is on the order of 1–10. For most microbes, in contrast, nu≪1. For example, for Escherichia coli, estimates of nu are on the order of 10−4 (Kibota and Lynch 1996). If s = 0.001, then ∼90% of such a bacterial population would have no deleterious mutations, in contrast to the case of human populations in which no individual with zero deleterious mutations would ever occur. For many microbes, then, Haldane load theory may be appropriate
They don’t vary the number of deleterious mutations. They use the same value even when varying the functional proportion of the genome.
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No where in their paper was I able to find that they use the same value for the number of deleterious mutations when varying the functional proportion of the genome. Could you show the relevant passage?