I think it is. If this type of accumulation results in extinction of a species then we shouldn’t see extant species with this much variation.
The more I’m trying to dig into this, the less I am convinced that Junk DNA has anything at all to do with GE. It deserves a mention just because people so often bring it up, thinking it’s relevant.
This comment seems to be built upon the false premise that all the variation we see between species is a result of mutation.
I am not really here but let me make a quick drive-by response. Perfect neutrality is nonexistent, of course. Population geneticists consider mutations neutral when they have so little effect that |s| << 1/(4N). In the more than 90% of the genome that is junk DNA, effects must be even smaller than that. In the maybe 5% of the genome that is not junk the mutations will cause more mutational load. Excessive mutational load is a worry for humans – the effect of the presence of junk DNA is that many of the mutations that occur in the genome are in junk DNA, so it affects the numbers. (There are people who claim that the purpose of junk DNA is to soak up these mutations harmlessly. I disagree, as do many molecular evolutionists, because as one adds junk DNA one most likely adds sites that are able to mutate, and most likely the total mutation numbers are proportional to the total amount of DNA.)
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If changing these bases is mostly detrimental it wouldn’t matter how they were changed.
Thanks again for contributing. I understand you’re saying that the majority of the effectively neutral mutations are happening in the junk region. But what I don’t understand is how this is supposed to prevent fitness decline from happening. Where are all the beneficials happening that are supposed to “counteract” the load of effectively neutral deleterious?
The last time I witnessed such a futile attempt to discuss a metaphysical notion was when the alchemist, John Dee, emailed me all about how angels don’t occupy physical space, and so you could have an UNLIMITED number of angels on the head of a pin.
It seems to me, that as long as you can maintain this “cerebral ruckus” over “junk dna” and “neutral mutations” - - you can say anything you want to your I.D. followers, because none of them understand these issues either.
How big are the deleterious effects of deleterious mutations in junk DNA? You should have been able to figure this out when I tried to hint it to you earlier.
Most of the diversity we see in life is not because of changes to existing information. It’s because life is pre-loaded with genetic diversity. It’s easy to whittle it down, like breeding a poodle from a stock of wolves over hundreds of years. But you cannot breed a wolf out of a poodle.
Individually, the effect is very small. But we aren’t talking about individual mutations. We’re talking about the cumulative weight of all of them combined.
No, we aren’t talking about the cumulative weight of all of them combined, because there haven’t been enough time in the history of the universe for all possible combinations of mutations in junk DNA to happen.
So price, now you need to start talking about the magnitude of the deleterious effects of mutations in junk DNA, and show with empirical evidence that given that magnitude, life as we know it should either already have gone extinct, or is close to it. Not some obscure date a hundred quadrillion googol years in the future.
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What if the selection coefficient of mutations in junk DNA is so small that all of them combined don’t weigh very much?
Is a 0.1% change in femoral length beneficial or deleterious? How about a 0.5 degree reduction in the angle of the mandibular ramus? A 1% increased expression of ADH1? A 0.2% reduction in the STAT5 induction from JAK2 signaling? Should I continue? If we played a game where you named a context independent mutations, and I named 5 context dependent mutations, how long do you think we could go?
I’ll close by simply noting you didn’t actually provide a single shred of evidence in support of your position that ‘most’ mutations are context independent, and that you didn’t even address the concept of movement from adaptive peaks.
Of course it does, because they are determining the DFE relative to an arbitrary initial context.
And is a 0.3% change in the diameter of the aorta have an equal effect on fitness in both? Of course not. Besides, any mutation that resulted in no heart and/or no lungs has a selection coefficient of 1, so is clearly irrelevant to any discussion of GE.
The genetic context is the interactions with the rest of the genome. The genetic context of allele A in genotype AB is different from the context of A in Ab. This is really basic stuff.
Then you’ve not read much of it. Not only is this well-established within population genetics literature (1,2), it is well-documented experimentally (3,4). And then you have the problem that DFE for humans is different from fruitflies, and that both have differences in DFE between different sequence types that aren’t necessarily even in the same direction. In other words, all of this must be done empirically for each species and sequence type. But if you’ve missed the literature of the past 15 years or so, I can understand how you might be unfamiliar with it. In any event, saying ‘I don’t know of anyone saying it’s different’ is not valid evidence that it is the same.
The qualifier I’ve put here is that most populations are well-adapted. Either you dispute this, or think that the groups you cite have been working with poorly-adapted populations and failed to mention it. You can find some of this discussed in (5), and also its references.
Remember here that only changes with fitness effects less than 0.5/Ne are even relevant. So while there are certainly many more ways to change a machine to damage it than improve it, the majority of those are >0.5/Ne. What’s left is minor changes, which are more likely to be contextual.
This entire section represents no more than a series of unsupported claims without evidential, theoretical, or even logical basis, and appears broadly to be completely ignorant of the majority of work in population genetics over the past 50 years.
In short, what I’ve presented is precisely the way mutations and fitness effects are treated within the literature. Ignoring your completely incorrect assessment of deleterious mutations being balanced by beneficial ones, you completely ignored the major point of that section as summarized by the TLDR, that the process is simply too slow under ideal assumptions. 10% in 25Ma? Please.
- The distribution of fitness effects of new mutations | Nature Reviews Genetics
- Estimating the Rate of Adaptive Molecular Evolution in the Presence of Slightly Deleterious Mutations and Population Size Change | Molecular Biology and Evolution | Oxford Academic
- Positive and Negative Selection on Noncoding DNA Close to Protein-Coding Genes in Wild House Mice | Molecular Biology and Evolution | Oxford Academic
- Contributions of Protein-Coding and Regulatory Change to Adaptive Molecular Evolution in Murid Rodents
- The Evolutionarily Stable Distribution of Fitness Effects - PMC
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That’s not what I meant. I mean the cumulative effect of all the mutations that are happening on a regular basis in a population. That’s what the DFE is talking about. Not “all possible mutations”, but “all mutations that are happening on an ongoing basis.”
Exactly.
As long as they weigh something, regardless of how small, then fitness decline is guaranteed. The only question is how long it takes.
No, fitness decline is not guaranteed. That doesn’t follow.
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How do you claim to know that? The answer to your question is not a function of the environment, but of engineering principles. Did your change result in greater circulation, or worse? More efficient use of energy, or less efficient? Our bodies are engineered. Tiny changes do matter. Ask any engineer.
Then explain why not. Just saying it’s small doesn’t answer anything at all.
Not true, for various reasons, some of which have been explained to you already. For one thing, the genome is of finite size, and eventually you just get multiple hits on a single site. Can we agree that if changing A to G at some site in junk DNA is ever so slightly deleterious, changing the G back to A must be ever so slightly advantageous, and changing the G to C or T has as much chance of being advantageous as of being deleterious? Notice that this isn’t about “breaking a machine”, as junk DNA can’t be considered a machine, having no function.
If it really has no function, then changes in it should not be deleterious or beneficial. They should be perfectly/strictly neutral. One of our resident population geneticists has already confirmed here that’s not the case. They do have an impact. This seems like a case of trying to have a cake and eat it as well.