Sure, but the function in that example is preserved because you have in fact conserved the elements necessary to function. At some point you could change your sentence so much it fails to function. But if your hypothesis is so flexible as to allow no relationship between sequence and function, it’s become effectively unfalsifiable and you can spend an eternity chasing your hypothetical function.
I’m not sure if indel rates have been modeled, but I see no reason to limit the model to just substitutions. We would also have to ask how indels and recombination events, both large and small, have no impact on function. If a transposon inserts into an expanse of neutrally evolving DNA, how is the alleged function kept intact?
To Rum,
If you haven’t done so yet, I’d encourage you to watch the entire John Mattick YouTube video, linked above. It’s fascinating and repays the time needed for watching.
In particular, focus on what Mattick says at the point I linked (about 32:13). He says:
“I want to say that conservation is totally misunderstood. High conservation imputes function, no question. Low conservation imputes nothing [meaning – low conservation does NOT entail absence of function, or neutrality; PN]. Think about your phone number…There’s gotta be something that’s different between us, and mice, and elephants.”
Conservation is a good place to start looking for function, sure.
But low (or no) conservation has, historically, been viewed as an evolutionary dump, littered with non-functional / neutral / generally uninteresting debris. The MAJOR motivator for that view was not careful functional analysis, but the theory of common descent, coupled with natural selection. Selection preserves what is important, and descent passes it on: QED.
Mattick, who is not an ID theorist (although Dan Graur, in a wildly intemperate moment, called him a “crypto-creationist,” a slander for which Graur owes Mattick an apology), realizes that focusing on conservation leaves molecular biology and evolutionary theory with a huge blind spot.
Evolution needs to explain why and how organisms came to be different. Focusing on what organisms share – the conserved stuff – is thus looking in exactly the wrong place.
No, that’s not what I’m saying. Look again at the mini-thought experiment (using English text) which I posted. Note what characters tend to be preserved in the jumble. Increase the randomization ever so slightly, by perturbing first and last characters, however, and meaning vanishes.
Not every sequence modification will be tolerated by selection (which is watching over essential functions).
True, but not really relevant to my criticism. It’s true that neutral changes can happen within functional sequences, and it’s also true that selected changes can happen (for a while) at a rate equal to or even greater than that of neutral drift. What you might mean to say is that this is not a reason to suppose that the bulk of apparent junk sequences are really under selection. And you would be right. We can rule out neutrality if a sequences is evolving either much more slowly or much more quickly than the neutral rate. If it’s evolving at the neutral rate, neutrality isn’t proven, but it’s the way to bet.
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But not as fast as they accumulate if there is no essential function to preserve. Your example even demonstrates this by restricting where ‘mutations’ can occur in order to preserve intelligibility; more ‘mutations’ could accumulate without that restriction.
Bidsees, your empaxle filas when filasbee armagnas are pisslobe.
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True, it does not ENTAIL it. It does however INDICATE it.
You are again creating this weird absolutist straw-man of the position you are attempting to criticize.
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So many “ID theorists,” but they’ve articulated exactly zero ID hypotheses and zero ID theories over decades. That’s a misleading label, given that they specialize in ad hoc denials like the one you’ve noted here–not theories.
That would be true. In the time I have studied the polymorphic (but highly function-rich, falsifying @gpuccio’s implicit hypothesis) genes encoding cardiac sarcomeric proteins, none have done so.
I couldn’t agree more. That may be because what he has been doing for decades is so very far away from doing science. Is that ever going to change?
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Function is better indicated by structurally defined interactions over cell cycles, not conservation, but that takes serious lab work to determine.
Lots of things are not conserved, like Orphan genes and systems!
Absence of function is not a claim, it is simply a conclusion. We don’t have our backs against the wall like you do.
Negative conclusions should be revised in the face of new evidence. You’re trying to frame science as mere debate.
But “all the time” doesn’t mean that any noticeable proportion of the genome classified as non-functional has been reclassified as functional.
If you agree, you might want to inform your DI colleagues about this, as they are constantly misinforming the public about this.
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How does that apply to DNA?
Then we should see sequence conservation in these regions, but we don’t.
Why? What are these “structurally defined interactions”? What would you use for a negative control (i.e. would completely random and functionless DNA also participate in these interactions)?
Some orphan genes do show signs of sequence conservation. Also, it is not assumed that orphan genes are functional simply because they are transcribed or translated. Even completely random and functionless DNA can be transcribed and translated by leaky genetic processes.
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No idea what you mean by “structurally defined interactions over cell cycles” but it sure sounds fancy and technical. You could just have said that a direct laboratory experiment is a better indication of function than conservation, and then you’d be right without sounding silly.
But being a better indicator than conservation does not imply conservation is NO or a POOR indicator.
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First off, your criticisms are completely fair and called for. Don’t let my subsequent writings detract from this fact.
Neutrality is proven in the colloquial sense of proven beyond a reasonable doubt. Neutrality is “proven” in the same way any other scientific hypothesis is proven, by observations that are consistent with the hypothesis and inconsistent with the null hypothesis. Proven in an ontological sense? No. Proven in a tentative, technical, contextual, and scientific sense? Absolutely.
Another way I like to put it is that once there is lots of evidence on one side it isn’t enough to simply say “Well, maybe it’s wrong”. Instead, there need to be REASONS why the current conclusions are wrong.
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The following shows deep conservation of motif that goes something like
xxxxxxxCxxCxxxxxxxxxxxxHxxxH
Each line with that motif is a separate zinc finger, there are about 13 of them. They create the same geometric fold, BUT it’s naive to think that just because we can vary the unconserved parts of the zinc finger and maintain the same fold that the the unconserved parts aren’t important!
In fact they are critical for the above protein to bind to a highly specific region of DNA in the genome, most likely to a regulatory target containing an ERV. If those unconserved regions are changed, it binds to the wrong section of DNA and function is compromised. We know from experiments even a slight compromise in zinc finger proteins such as these can lead to a disease state.
Also, something can be highly conserved but there is little to no lab evidence it was the result of selection. This has been noted in studies like this one by Behe in the peer-reviewed journal Trend in Biochemical Science:
https://www.sciencedirect.com/science/article/abs/pii/096800049090231Y?via%3Dihub
recent experiments have determined that, although core histone sequences are highly conserved among eukaryotes, large regions of the proteins are dispensable for growth in yeast.
This mantra that conservation absolutely implies selection has been falsified manytimes. It only may suggest it.
The problem is that things can be knocked out, and because of redundancy, selection can’t directly select against a change!
But conservation does IMPLY selection. Nobody says the relationship is “absolute”, whether in terms the certainty with which the inference is made, or efficacy of selection to preserve a sequence. Both you and Paul Nelson are working overtime to uphold this misleading absolutist strawman of the inference of selection from conservation.
Only by exaggerating the conservation argument into some absolutist claim (conservation proves function to an absolute certainty, lack of conservation proves nonfunction to an absolute certainty) can you then turn around and declare it falsified when exceptions are found.
The problem is, it is a strawman of your own making. The relationship between the rates substitution and the inference of selection both comes in degrees and is fundamentally based on a probabilistic framework. A question you could ask is, if these sites are not being preserved by natural selection, what is the probability that under the assumption of X rate of change, they should have remained unchanged over this span of time? This question is based on a probability of occurrence of a certain event. It logically CANNOT entail an absolute claim of function or non-function.
That is also why it can only ever give an INDICATION of function vs non-function. When you and Paul Nelson keeps pretending otherwise, you’re being misleading. If you keep doing it, we’ll be forced to conclude you’re doing it intentionally.
Ok, lab experiment is a SUPERIOR indication of function than conservation or selection.
Also, we’re now seeing evolution requiring simultaneous co-evolution in structures. I call it the nuts and bolts or lock-and-key problem. If we change a bolt, the properly fitting nut has to be changed too. Same for locks and keys.
When regulatory regions are changed by evolution and these regions are the targets of certain proteins, the proteins have to be changed simultaneously for function to be preserved. This has led to the outrageous claim, for exmaple, that zinc finger proteins must “co-evolve” with the regualtory ERVs or SINEs which the zinc finger proteins target!
So, just because we look at a family of zinc finger proteins and see the proteins have huge unconserved regions, it doesn’t mean those regions are functionless!
The way function can be determined is whether the proteins are strcutrually connected at some point during the cell cycle to a region of DNA. By way of extension we can see structural connections in protein-protein binding in complexes. I suspect we’ll see lots of “co-evolution” (a euphemism for co-varying designs).
This sort of functionality will not be apparent by dismissing non-conserved regions as functionless. That’s really naive in light of what we know now.
One interesting complex to explore are the polymerase complexes like this:
One would think every bacterial species would have at least one polymerase subunit conserved across all species. That is not the case. Just because we find a rare orphan subunit, which by definition is not conserved, does that mean it’s functionless? NO. That’s would be absurd because polymerases are life critical.
The structure and mechanical interaction and connection of the parts is a better definition of function than natural selection or conservation.
Oh look, Sal Cordova is back to spamming pretty figures and posting walls of technical sounding stuff. zzzZZZ.
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Aaaand the goalposts went flying. Now we could spend hours sitting here playing wack-a-mole and Gish-gallop trying to refute and explain concepts as fast as Sal can spam the thread with new ones.
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Structural Biology is advancing the case for design as the diagrams from Structural Biology show visually why proteins are improbable.
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