Genetic load: can someone explain?

So, let me see if I've got this right. The idea is that, if deleterious mutations exhibit synergistic epistasis, the fitness will eventually stabilize due to selective pressures. Correct?Whether this idea is correct or not seems to be very important to both sides of the EvC debate. Dr. John Sanford in his book Genetic Entropy & the Mystery of the Genome made an argument against the leveling of the deterioration and I think this could be the most important part of his book and thus the creationism movement. I'm hoping you know basically what the book is talking about already, because I don't want to quote a lot of the book if I don't have to. Read the chapter - Crow to the rescue? - if you can. Here is what he said in response to this model:

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Assuming artificial "truncation selection", based solely upon "mutation count per individual", mutations accumulate to high numbers - but their increase eventually starts to taper off. However, the nature of this curve is surprising, in that it still shows a disastrous accumulation of mutations.... the population plummets essentially to zero... in just 300 generations.(107)

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I can try to get more information on the exact numbers he uses later if necessary, but a question naturally arises regardless: Is the equilibrium (so to speak) of the population soon enough as to prevent problems for the evolutionary theory? Would it be correct to assume that we simply do not know yet? Dr. Sanford continues:

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The first, which is of minor importance, is the question - "Who has the most mutations?" The second, which is of primary importance, is - "Who has the worst mutations?" The model described by Crow only considers the former, while ignoring the latter....One person may have several thousand fewer mutations than another, yet just one specific mutation can still make that person much less fit. Therefore, the idea of counting the total number of mutations per individual, and then selecting away high-count individuals can not be considered a reasonable natural mechanism to get rid of more mutations.(107-109)

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I'm not sure if this is correct or not, but on first glance it sound reasonable. Basically, his claim is that natural selection is not powerful enough to select against an organism with the most mutations because all mutations are not equal. The individuals with the most harmful mutations will be weeded out while the organisms with the most mutations will be left behind. Whether that poses a problem for the evolutionary model or not I am unsure, but he sure seem to think so. Interestingly he goes on to discussion synergistic epistasis:

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But even if it were valid, it makes the genetic situation worse, not better. We have always known that genetic units interact, and we know that such epistasis is a huge impediment to effective selection....If multiple mutations really do create damage in a non-linear manner, then error catastrophe would happen much sooner and populations would spiral out of control much faster - into mutational meltdown.(110)

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This was actually my first impression of this as well. I'm curious as to if synergistic epistasis will actually help or harm the theory. How exactly does an increase in effect of deleterious mutations help? Is this supposed to make the mutations more visible to selection? Let me go ahead and put his final word because I already discussed the others:

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...it should be pointed out that Crow's argument only addresses the problem of cost of selection. So even if Crow's model could be shown to be sufficient and fully operational in nature, the human genome should still deteriorate...(111)

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He goes on to talk about problems he has discussed earlier such as near-neutral mutations. One of his assumption seems to be that the mutations are not near-neutral in the graphs that produce a leveling out of the curve. Is that correct?Dr. Sanford seems to be a well respected evolutionary scientist and certainly knows more than me, so I want to believe he is correct, but he is not a population geneticist, so it is well possible he is incorrect. What do you guys think? Again, I tried to quote only that which was necessary for debate, so If you need clarification, simply ask.Edited by Phydeaux, : No reason given.

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I'll respond in more depth when I have the time, just in the meantime I would say. I still don't see how this is necessarily a problem for evolution? It might be a problem for the human race when it becomes extinct but I don't see why it is a problem for evolution.

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Well, it really depends. If the build up of deleterious mutations is only due to medical advances, then it is not a problem for evolution, but if deleterious mutations are always building up regardless of medical advances, then this is obviously just as much a problem for australopithecus as it is for humans. We can't evolve if genetic load kills us first. Further more, we can't build up function building mutations if we have more deleterious mutations than function building mutations.Edited by Phydeaux, : No reason given.

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If evolution, and these deleterious mutations, have been going on for several billion years, I wouldn't worry about them too much. We're doing just fine in spite of being proclaimed doomed because of this problem.
Where deleterious mutations would become a real problem is when one believes that the buildup of these mutations has been going on for just 6,000 years (since The Fall), and that its been all downhill since then.

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But since there is no empirical evidence for either a 6,000 year old earth, or a "fall from perfection," and since the evidence shows billions of years of successful evolution, we don't need to worry about it, eh?

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Well, first, you just ignored old earth creationism/ID. Second, the question of what the evidence says is exactly the question we are here to discuss. The mutation rate and genetic load is part of the evidence. I think it is rather foolish to ignore evidence in any case. Sure, pointing to other evidence and saying this evidence over here is more convincing is perfectly reasonable, but you should also acknowledge that there is evidence against the theory (if this is actually evidence against the theory).

I think you misunderstand what I am saying. I never said anything about the fall. The timing of a genetic meltdown has nothing to do with the age of the earth or the fall. The meltdown has to do with the rate which deleterious mutations are accumulating.Edited add: Just so you know, I'm not a YEC nor a OEC. I'm not even an ID proponent. I have yet to make up my mind on these issues because there is just so much left to learn. I lean towards those things and I will make arguments for those things, but I will not claim I know one of these are true because I do not know. I only defend these ideas so the theories can be tested through debate. So, please don't assume I support the fall or Noah's Ark etc...Edited by Phydeaux, : Edited add

He is pretty qualified because he was a plant geneticists, but the general idea I get from his book (I don't know if you have read it) is that he always looked up to the population geneticists as geniuses of whom he was not worthy to question. Not very long before he published his book he was converted into a YEC. I assume that it was then he first really started to dig through the literature of the population geneticists because he presents the finds as if he was surprised to find it like if he never would have expected he didn't know about it for all the years of his research. For this reason I question how well he understand population genetics. He certainly is qualified, but I think his arguments should certainly be read with caution.Edited by Phydeaux, : No reason given.

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Obviously the human population is not "essentially zero", so humans must have been around for less than 300 generations, right ?

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That would fit quite happily with a timescale of 6000 years, but not with an Old Earth timescale (which cannot be much less than 200,000 years).

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I believe that is just with Crow's data on 1-2% per generation. I know Sanford doesn't think it will be 300 generations from now though. Even in chapter 10 he says that 300 generations from now may not be enough to destroy the genome and that it may take 300,000 generations or 6 million years. (150) You can also look at his work with Mendel's Accountant which in no way suggests 300 generations (if I read the charts correctly). The fact is however, we don't have enough data be sure of how fast the degeneration of the genome is, if it is degenerating at all, so exact time scales are unsure.Edited by Phydeaux, : No reason given.

You can read prologue along with page 46 for were I'm getting my information.

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So well I would think that he is considered knowledgeable enough to peer-review papers on the subject, than he probably is enough to write on it.

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Fair enough.

Sanford was basing the 300 generation thing on Crow's estimates of a decline of 1% per generation. This came from a paper by Crow. I just now looked it up and this is what it states:

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If we are like Drosophila, the decrease in viability from mutation accumulation is some 1 or 2% per generation.(Crow, J.F. 1997. The high spontaneous mutation rate: is it a health risk? PNAS 94:8380-8386)

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Sanford's calculations with Mendel's Accountant use perimeters of humans rather than Drosophila. Maybe that is why.Sanford's model still sees a crash, but it isn't in 300 generation. He never claimed it is 300 generations. As far as I can tell, he was only using Crow's model to prove that even with his numbers we see a crash. He wasn't trying to prove that 300 generations is the correct time.

Look, I could go through and try to find out what was wrong with Crow's model, but I really see his model as irrelevant. If Crow's model is wrong, that doesn't mean Sanford's model is as well and it doesn't mean the genome is not deteriorating. I don't really care about Crow's model.