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Author Topic:   Genetic load: can someone explain?
NosyNed
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Posts: 8867
From: Canada
Joined: 04-04-2003
Member Rating: 8.0


Message 16 of 53 (488829)
11-18-2008 9:26 AM
Reply to: Message 15 by Wounded King
11-18-2008 7:12 AM


Clearer good words (shorter)
Thank you. I understand all the words now and the different cases makes sense.

I would guess that the independent or synergistic effect cases are the more common?

I think I could now tie this back to the OP but I'm going out (and would rather someone else (who might get it right) did it first. (Later I will try).

Then I'll have to review the information to see the evidence for the synergistic case in humans.


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NosyNed
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Posts: 8867
From: Canada
Joined: 04-04-2003
Member Rating: 8.0


Message 17 of 53 (488845)
11-18-2008 1:27 PM
Reply to: Message 15 by Wounded King
11-18-2008 7:12 AM


Re: Good words, but what do they mean?
From the OP:
If mutations interact multiplicatively,

So this basic assumption must be met. If they are synergistic then deleterious mutations do not pile up and become such a problem. That is the average fitness does not drop to as low as 0.05.

Right?

However, I know realize that I don't know how "average fitness" is determined or what it means. It seems to suggest that if it is 0.5 then half of offspring survive to reproduce. That makes some kind of sense.

Now then how do we decide if it is actually synergistic?

It makes sense to me that it might be. Obviously, there will be cases where having one moderately deleterious mutation might not be enough to stop reproduction but a second one is fatal? Correct?


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 Message 15 by Wounded King, posted 11-18-2008 7:12 AM Wounded King has responded

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Wounded King
Member (Idle past 2416 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 18 of 53 (488901)
11-19-2008 9:14 AM
Reply to: Message 17 by NosyNed
11-18-2008 1:27 PM


Epistasis and fitness
Now then how do we decide if it is actually synergistic?

By post hoc measurements of survival or mating success, the same way we would determine what the fitness is for an individual mutation. If we can measure the fitness cost for each deleterious mutation independently and together we can see if the combined fitness cost is multiplicative or synergistic.

Obviously, there will be cases where having one moderately deleterious mutation might not be enough to stop reproduction but a second one is fatal? Correct?

Certainly. The most obvious case, although not a very likely one, is if if you had 2 distinct deleterious mutations in different allelic copies of the same gene, where only 1 wild type allele was required for normal wild-type fitness. Each in isolation would have little effect but having the 2 simultaneously would be severely detrimental.

It is much harder to call if the deleterious mutations in question are in completely different parts of the genome and possibly not even involved in the same developmental/metabolic pathways. This is why we can only really use post hoc methods to investigate the interactions of multiple mutations. The other research approach taken relies principally on extensive theoretical modeling but obviously this can't tell us what situation actually obtains in human genetics.

For an idea of how complicated investigating epistasis is, even in the comparatively simple context of E. coli, take a look at Beerenwinkel et al.(2007).

Beerenwinkel et al writes:

Epistasis occurs whenever mutations interact non-linearly with one another, and it represents a major challenge in describing the mathematical structure of real fitness landscapes. With epistatic interactions, the combined effect of two or more mutations on fitness may be greater than, less than, or opposite in sign to expectations obtained by combining their separate effects. A growing body of empirical research indicates that epistasis is very common in nature [references removed]. However, a complete mathematical description of epistatic interactions has not been forthcoming for any system because the forms of epistasis appear to be diverse, idiosyncratic, and hence complex.

TTFN,

WK


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Phydeaux
Junior Member (Idle past 3524 days)
Posts: 13
Joined: 11-17-2009


Message 19 of 53 (535739)
11-17-2009 4:35 PM
Reply to: Message 18 by Wounded King
11-19-2008 9:14 AM


Re: Epistasis and fitness
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:

quote:
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)

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:

quote:
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)

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:

quote:
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)

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:

quote:
...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)

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.


This message is a reply to:
 Message 18 by Wounded King, posted 11-19-2008 9:14 AM Wounded King has responded

Replies to this message:
 Message 20 by Wounded King, posted 11-17-2009 6:02 PM Phydeaux has responded
 Message 27 by slevesque, posted 11-18-2009 2:09 AM Phydeaux has responded

  
Wounded King
Member (Idle past 2416 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


(1)
Message 20 of 53 (535754)
11-17-2009 6:02 PM
Reply to: Message 19 by Phydeaux
11-17-2009 4:35 PM


Re: Epistasis and fitness
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.

TTFN,

WK


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Phydeaux
Junior Member (Idle past 3524 days)
Posts: 13
Joined: 11-17-2009


Message 21 of 53 (535762)
11-17-2009 6:42 PM
Reply to: Message 20 by Wounded King
11-17-2009 6:02 PM


Re: Epistasis and fitness
quote:
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.

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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 Message 22 by Coyote, posted 11-17-2009 9:13 PM Phydeaux has responded

  
Coyote
Member (Idle past 427 days)
Posts: 6117
Joined: 01-12-2008


Message 22 of 53 (535771)
11-17-2009 9:13 PM
Reply to: Message 21 by Phydeaux
11-17-2009 6:42 PM


Deleterious mutations
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.

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.

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?


Religious belief does not constitute scientific evidence, nor does it convey scientific knowledge.

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Phydeaux
Junior Member (Idle past 3524 days)
Posts: 13
Joined: 11-17-2009


Message 23 of 53 (535773)
11-17-2009 9:24 PM
Reply to: Message 22 by Coyote
11-17-2009 9:13 PM


Re: Deleterious mutations
quote:
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.

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?


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).


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Coyote
Member (Idle past 427 days)
Posts: 6117
Joined: 01-12-2008


Message 24 of 53 (535776)
11-17-2009 10:23 PM
Reply to: Message 23 by Phydeaux
11-17-2009 9:24 PM


Re: Deleterious mutations
Well, first, you just ignored old earth creationism/ID.

With old earth creationism we have billions of years of evolution, and no "fall" about 6,000 years ago. The argument that deleterious mutations are going to get us "real soon now" after billions of years doesn't scare me in the least.

Second, the question of what the evidence says is exactly the question we are here to discuss.

Evidence, yes. Scripture and "divine" revelation are not evidence. The idea of "the fall" is a religious belief, not a scientific finding.

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).

If the deleterious mutations are suddenly going to get us, with this "genetic load," after billions of years, perhaps we could be provided with a mechanism, and a reason for such a drastic change after all this time.

I think the belief in a young earth and "the fall" is behind this so-called science. With an old earth and no "fall" there doesn't seem to be a problem at all, no matter what creationist authors claim.


Religious belief does not constitute scientific evidence, nor does it convey scientific knowledge.

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slevesque
Member (Idle past 2962 days)
Posts: 1456
Joined: 05-14-2009


Message 25 of 53 (535799)
11-18-2009 2:04 AM
Reply to: Message 22 by Coyote
11-17-2009 9:13 PM


Re: Deleterious mutations
You seem to be equivocating the fact of evolution with the theory of evolution, invoquing that since we know the former is ''true'' (I don't think it is, but from your point of view) then obviously the later is true as well.

But it doesn't follow. Neo-Darwinian evolution as a theory uses two mechanisms: mutations and natural selection. This is supposed to be able to explain the fact of evolution shown by the fossil record, amongst other things (which by the way, shows much more ponctuated equilibrium in my humble opinion.)

But if Mutation+NS is being discovered to be unable to provide the fact of evolution, then other avenues must be searched. Possibly a third mechanism that, added with the two others, can be shown to produce the evolution of a population. At this stage, the fact of evolution has not being challenged.

But I do not think, and you will probably agree with me, that you can really bring up the fact of evolution, and through it protect the Neo-Darwinian theory of evolution. If simple mutations+NS is shown to be unable to produce the fact of evolution, than other avenues must be searched.

Rereading your post before sending mine, this is not exactly what you are doing. I still post it anyways as I find it a good addition to the overall discussion.


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slevesque
Member (Idle past 2962 days)
Posts: 1456
Joined: 05-14-2009


Message 26 of 53 (535800)
11-18-2009 2:08 AM
Reply to: Message 24 by Coyote
11-17-2009 10:23 PM


Re: Deleterious mutations
I think he was more talking about the evidence brought up by modern genetics. (number of mutations per person per generation. Beneficial to deleterious ratio of these mutations. The danegrs of mutational meltdown, etc.)

You always seem to be bringing up the fall for whatever reason I don't know. And you tag it here as the evidence Phydeaux is talking about, which it clearly was not.


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slevesque
Member (Idle past 2962 days)
Posts: 1456
Joined: 05-14-2009


Message 27 of 53 (535801)
11-18-2009 2:09 AM
Reply to: Message 19 by Phydeaux
11-17-2009 4:35 PM


Re: Epistasis and fitness
I think Dr. Sanford sometimes peer-reviews papers in the domain of population genetics, so he is pretty qualified in the field I would guess.

This message is a reply to:
 Message 19 by Phydeaux, posted 11-17-2009 4:35 PM Phydeaux has responded

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Phydeaux
Junior Member (Idle past 3524 days)
Posts: 13
Joined: 11-17-2009


Message 28 of 53 (535802)
11-18-2009 2:18 AM
Reply to: Message 24 by Coyote
11-17-2009 10:23 PM


Re: Deleterious mutations
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


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Phydeaux
Junior Member (Idle past 3524 days)
Posts: 13
Joined: 11-17-2009


Message 29 of 53 (535803)
11-18-2009 2:39 AM
Reply to: Message 27 by slevesque
11-18-2009 2:09 AM


Re: Epistasis and fitness
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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PaulK
Member
Posts: 15578
Joined: 01-10-2003
Member Rating: 2.9


Message 30 of 53 (535806)
11-18-2009 3:26 AM
Reply to: Message 28 by Phydeaux
11-18-2009 2:18 AM


Re: Deleterious mutations
I think that you miss the point. The timing will be affected by the start point.

If your quote accurately reflects Sanford's views, he says:


...the population plummets essentially to zero... in just 300 generations.

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

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).


This message is a reply to:
 Message 28 by Phydeaux, posted 11-18-2009 2:18 AM Phydeaux has responded

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