No. Are you admitting you’re misleadingly picking what you see as weaker arguments to present as substantive?
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Last time. What is the substantive argument against GE involving Junk DNA?
Most succinctly, that you have no evidence that your imagined DFE of mutations obtain in junk DNA. It’s not exclusive to junk DNA of course, but it applies there too.
That is what I think is the most substantive critique of GE from junk DNA is, but I don’t think that’s at all the most substantive critique of GE. I’ve already summarized what I think those are, above.
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This sounds like you’re suggesting that a substantial proportion of mutations in Junk DNA are beneficial (otherwise I cannot see the relevance of your statement). Is that what you mean to suggest?
Then I emplore you to spend more time thinking about it.
May I suggest you try an exercise here? It goes like this: You are to take it as a premise, for the purposes of this exercise, that what I am suggesting below is true:
A) That mutations in junk-DNA do not cause inevitable and sustained GE until extinction.
B) That they don’t need a substantial proportion to have strictly neutral effects.
C) That they don’t have to have a substantial portion of beneficial effects.
Now, the tricky part will be for you to try to imagine what would have to be also true, for what I suggested above to be true too. I promise you this is possible, and the results may even surprise you.
No.
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The obvious objection I see is that GE requires that effectively neutral mutations be overwhelmingly deleterious, but if the junk DNA is either not transcribed or the transcribed RNA is not used or the transcribed RNA generates nothing that has an effect, then the only impact of point mutations will be to very very slightly change the impact of replicating/transcribing/protein-generating, and that impact is going to be based solely on which nucleotide is replaced with which other nucleotide, and won’t be much biased in either direction beneficial or deleterious, but will tend to equilibrium. .
This is definitely not one of the strongest criticisms of GE - which may be why you’re concentrating on it.
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We’ve sequenced the genomes of hundreds of different species going back to 700,000 years ago and all show substantial amounts of junk DNA. GE is based on the premise all genomes were created “perfect” only 6000 years ago. What is GE’s explanation for all the junk DNA we see in those other thousands of genomes? Why would a “perfect” genome have large amounts of junk DNA?
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You neglect a third category of functional, non-transcribed DNA: regulatory sequences such as transcription factor binding sites. But that doesn’t affect your point, since functional DNA of any sort is only a small portion of the human genome.
My major objection is that a) the fitness effects of mutations are dependent on the particular environmental and genetic context in which they occur, and b) most populations are reasonably well-adapted. Given these two points, the expectation is that any mutations with any effect will be likely to move away from that adaptive peak by some minor degree, making them deleterious in that context. As this context changes, the fitness effect in the new context is as likely to be beneficial as deleterious relative to its effect in the prior context. This can shift the magnitude of slightly (that is, nearly neutral) beneficial or deleterious mutations fitness effects to the other side of the selective threshold.
TL;DR: GE only works if fitness effects are fixed, but they are not.
I also take issue with the presentation of established distributions of fitness effects in particular types of sequences (for instance, DFE for coding regions) as applicable to other types of sequences without specific supporting evidence. It is certainly the case that non-synonymous mutations in coding regions have a predominantly deleterious DFE, however this evidence does exactly nothing to support any DFE for synonymous mutations in coding regions, much less, non-coding regions with regulatory significance, much less non-conserved non-coding regions.
TL;DR: GE makes an unsupported extrapolation of coding DFE to all sequences.
Additionally, GE generally fails to grapple with just how small the selection coefficients of the nearly neutral mutations are. Nearly neutral in humans is ~10^-5, which works out to 250ka for a 10% fitness reduction with the most generous possible assumptions for GE. But the average fitness effect of nearly neutral mutations is much less than the threshold, partially because some are beneficial but mostly because the probability of mutations with smaller effects is greater than that of those with larger effects. Kimura put the mean fitness reduction per generation at less than 10^-7, or 25Ma for a 10% reduction in fitness. Assuming this estimate to be accurate, balance could be achieved with a single beneficial mutation just above the threshold every 100 generations or so.
TL;DR: GE would be too slow to be meaningful even under the most generous assumptions.
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In that case I still can’t draw anything coherent from your response. Maybe you could try framing it in a positive statement, rather than a negative one. Stop focusing on saying what I allegedly don’t know, and say something positive about how Junk DNA somehow invalidates GE. Don’t ask me to try to figure out what you mean. It’s enough already.
I know, but those aren’t junk. I’ve fixed my post though.
This is clearly a wrong statement. Sure there are some traits that will be beneficial in some environments and not others, but it’s very obvious this will be a minority compared to the number of traits that are going to be beneficial/deleterious regardless of environment. Indeed, the very idea of producing a DFE for all mutations (as the population geneticists such as Kimura have undertaken to do), makes absolutely no sense if what you’ve said here is true.
Both polar bears and black bears need a functioning heart and lungs.
The genetic context of a mutation IS fixed. That’s its location in the genome. Or do you suggest that mutations can move around after they’ve happened?
The population genetics literature I’ve read has done nothing to suggest a wildly different DFE for different regions of the genome. The literature I’ve seen appears to discuss mutational affects without much regard to their specific location in the genome. They’ve been very open to admit that the vast majority are deleterious (without such qualifications as you’re attempting to insert here). This is based not only on data, but also on pure logic. It’s always much easier to cause damage to a machine (or to information) than it is to improve upon it.
Fitness is not a substance. The damage mutations do is to information. One positive change can’t undo another negative change. Just like if I go through my post here and I make one bad typo, and one good one; I still have a bad typo. The good one didn’t take away the bad one.
That means you cannot appeal to one large-size beneficial mutation as if it could somehow erase thousands of much smaller deleterious ones. That’s not how information works.
Though it’s seriously overused, there are times when it’s appropriate to mention Dunning-Kruger syndrome. This is one of those times. The confidence with which @PDPrice asserts falsehoods and nonsense is jaw-dropping. I’m assuming that @CrisprCAS9 can take care of himself, so that’s all I wanted to say.
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That’s what everybody thinks, every time they use it. That’s why it’s so overused.
Since population genetics is a science they do need objective and measurable criteria for determining if a mutation is beneficial, detrimental, or neither. That would have to come in the form of measured fitness, sequence conservation, and fixation, to name a few. This is what @glipsnort was getting at when he said effectively neutral was redundant because neutral implies effect. We can come up with subjective opinions on what impact a mutation may have, but it wouldn’t be scientific.
The definition of the word neutral implies no effect. That’s why we have to qualify it. Pop gen scientists refer to effectively neutral mutations, which do have an effect. Strictly neutral ones are believed to be nonexistant.
They are effectively neutral, which is all that matters. If a 1 base insertion requires the cell to use a few extra ATP molecules to replicate the genome that would be an energy cost, but does it really matter? No. It’s a drop in the bucket compared to the overall energy budget of the cell.
I would say that it is a test for GE. If these mutations are as problematic as you claim then why do we see boatloads more variation in junk DNA, especially when we compare genomes between species. We don’t see sequence conservation in these regions. It wouldn’t matter if this variation is due to mutations or design because the implications for fitness would be the same.
What I think you need to explain within GE is why we see way less sequence conservation in these regions.
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You’re asking me to try to refute the idea that junk DNA exists. That’s a different question. I’m asking how the existence of Junk DNA is supposed to counteract what we have established: that most mutations are damaging, and that there is a class of mutations called effectively neutral which are invisible to natural selection. The only way this would not result in deleterious accumulation is if you could somehow make a case that either 1) they are not effectively neutral but strictly neutral (pop gen scientists reject this option) or 2) they are evenly matched between deleterious and beneficial such that there is no accumulation (or rather, you really need more beneficial than deleterious in order to get positive evolution). And even this latter option is unrealistic based upon how information works, as I noted above.
Most mutations are effectively neutral. That is what junk DNA tells us. If GE is true then we shouldn’t see as much variation between species in these regions.
Ok, but that’s not a refutation of GE. Sanford acknowledges and even works off of this fact.