If that is what he is talking about, it is irrelevant. The test of common descent we are discussing would work just as well if we were talking about random strings of letters generated by a computer. Issues of waiting time, selection, function, etc do not pertain.
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that reference does not support the claim for which you were asked for a reference, here highlighted in bold:
for instance: if we need at least 3 specific amino acids to get a new function (in many cases we will probably need more than that).
You give a reference to a study on ONE protein that required two neutral permissive mutations before a third enabled a new function. Are you aware of even one single other such example, or is this literally the only one you know?
Oh and by the way(as I have explained to you multiple times before about that reference), that paper doesnât show that those 3 specific mutations are the only ones possible that enable the new function. They are merely the only ones found among the thousands of variants tested. Claiming that therefore no other such mutations exist that could facilitate such a functional switch would be to claim something the evidence does not support.
Much less does it support your blind, unsupported assertion that there are âmany casesâ where we âprobably need more than thatâ. You just made that up out of nowhere.
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He seems to have ignored the paper I cited wherein it took one mutation to evolve a new promoter for genes of the Lac operon and this happened in a week or two.
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Yes, and contrary to his one example where only two mutations were found among the few thousand tested, many other references can be given where experiments reveal that a new function could evolve with less than 3 mutations, while these articles also show that many alternative mutational combinations that enable the new function, are possible.
The reference he found is actually highly unusual because itâs the only example I know of where only two specific mutations were found among those tested, that enabled the new function to evolve. And again, because many more mutations are possible than those tested, he canât just extrapolate that to mean no other such mutations exist, nor generalize this to mean there must be many more worse cases.
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note that in this case at least few mutations are required only to improve an existing function (improving binding actually). thus, we can conclude that we need more than just few mutations to get a completely new function. (i came across an article recently, that also probably talks about a number of specific mutations but I do not find it at the moment).
according to the author: âIf our results are general - and we think they probably are - then many of our bodyâs systems work as they do because of very unlikely chance events that happened in our deep evolutionary past,â.
from the article: " In screening thousands of alternative histories, the researchers found no alternative permissive mutations that could have allowed the proteinâs modern-day form to evolve". âAmong the huge numbers of alternate possible histories, there were no other permissive mutations that could have opened an evolutionary path to the modern-day GR,â Thornton said"
so what makes you think otherwise?
More recent research from the same lab, for one thing:
The study, published this week in Nature by UChicago graduate student Tyler Starr and Prof. Joseph Thornton, is the first to subject reconstructed ancestral proteins to deep mutational scanningâa state-of-the-art technique for characterizing massive libraries of protein variants. The authorsâ strategy allowed them to compare the path that evolution actually took in the deep past to the millions of alternative routes that could have been taken, but were not.
Starting with a resurrected version of an ancient protein that evolved a new function some 500 million years agoâa function critical to human biology todayâthe researchers synthesized a massive library of genetic variants and used deep mutational scanning to analyze their functions. They found more than 800 different ways that the protein could have evolved to carry out the new function as well, or better than, the one that evolved historically.
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I donât know which of the papers you are referring to, but if it is for the one I cited, then you are blatantly misrepresenting the study. It took one mutation to evolve new promoter function in over 60% of the random sequences, and subsequent mutations to improve that function. Getting a new function and improving on that new function are two different events. Why are you being openly dishonest? Look at the study chart (Fig a) again:
You canât find it because it doesnât exist.
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The protein evolved reduced sensitivity to steroid hormones, not âimproved bindingâ. Itâs actually characteized as a degradation in function, by the authors. It is unique in that the functional degradation happened to constitute an across-the-board reduction in sensitivity to the different classes of steroid hormones the protein responds to.
Reconstruction and experimental analysis showed that AncCR, like the extant MRs, was extremely sensitive to both mineralocorticoids and glucocorticoids, and its structure was MR-like, as well [19]. Subsequent work revealed that GRâs specificity for glucocorticoids evolved later in the lineage leading to bony vertebrates, after the divergence of cartilaginous fishes but before the split of ray-finned fish from the lineage leading to tetrapods and lobe-finned fish, due to a small specific set of historical mutations [15], [16], [19] (Figure 1).
The evolutionary causes of GRâs reduced hormone sensitivity are not known. In the little skate â the only cartilaginous fish studied to date â GR is a low-sensitivity, broad-spectrum receptor: like MR, it responds to both glucocorticoids and mineralocorticoids, but it is unique in requiring high concentrations of either type of hormone to activate it.
(âŚ)
We first resurrected the LBD of AncGR1 (Figure 1) â the GR protein present in the common ancestor of bony and cartilaginous vertebrates and the earliest node after the GR-MR split â and then used functional assays, X-ray crystallography, site-directed mutagenesis, and computational predictions of biophysical parameters to dissect the mechanisms by which GR evolved. We show that after its initial birth by gene duplication, a small number of mutations that partially degraded its structure, stability, and function caused GR to become a novel low-sensitivity receptor.
But you can obsess about what exactly you mean constitutes a ânewâ function until the end of time, it doesnât make anything you say true or well supported.
No, we canât do that, youâre making that up. And you havenât defined what you mean by a âcompletely new functionâ - so since youâd now have to do it ad-hoc, that definition will constitute a moving of the goalposts since YOU cited THIS study to show that a functional shift GENERALLY requires 3 mutations or more.
Youâre making shit up as you go, and changing conditions to try and save an already failed argument.
ROFL.
That says nothing about only 3 specific mutations being the only ones possible for the evolution of the functional switch, much less does it support your fatuous generalization that âin many casesâ âprobably more are neededâ.
And heâs speaking about those tested. We know because the author is not an idiot, is generally a clear and careful communicator as anyone who reads his papers can tell, and donât speak to conclusions his data cannot support.
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SCD is probably going to shift the goal posts again.
800+ is a huge number though. Its nothing short of amazing.
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And that is just for one specific function involving binding to one specific sequence of the steroid hormone. How many pathways would lead to the same function thru binding to a different sequence? Or a different function altogether?
Maybe some ID âresearcherâ would care to try answer those questionsâŚ
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These are good questions and are probably being worked on somewhere. Its relatively easy to read published papers, but the doing studies is quite difficult. Kudos to Thornton and people who have done good research in it.
We wish.
yep. my bad. i probably refer to a similar experiment (and by the way i didnt read the paper, just gave it as a reference), but its still about changing an existing function.
i dont think so. dont you agree that proteins from the same family are closer to each other than proteins from a different family?
a new binding site for instance.
i was referring to my paper. not about new promoters.
dont be sure about that: âHe then synthesized a library of ancestral proteins containing all possible combinations of amino acids at the four key sites in the receptor that recognize DNAâ160,000 in all, comprising all possible evolutionary paths that this critical part of the protein could have followed. Most of the variants failed to function at all, and some maintained the ancestral function. But Starr found 828 new versions of the protein that could carry out the new function as well,â-
so out of 160,000 possible combinations only about 800 could do the job. thus, only one in about 200 combinations will give us the correct order. so not only we need to change up to 4 bases, but we also need to mutate these bases 200 times.
again, this is just to change an exisitng function. not even a new one, which probably require more mutations. why do you think for instance that all different OR (olfactory receptors) are still OR?
You mean: Why do all the receptors that currently function as part of the olfactory system currently function as part of the olfactory system?
When you reword the question in a more reasonable way like that, it sort of answers itself, doesnât it?
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im asking why all these OR are still a type of OR after all their evolution. the answer is quite clear: it takes more mutations to evolve a completely new function. this is why there are so many variations of OR, probably since all of them are near each other in the sequence space.
Yes, it is.
But thatâs not it.
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you realy think that the genetic distance between two ORâs is larger than between OR and completely different proteins such as globin and keratin?
No.
Why do you ask?
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What does family have to do with switching function? Nobody is claiming all protein families are evolutionarily related.
A single protein family can have many different functions, so the amount of differences that separate different families is no indication of the mean number of differences it takes for some protein in such a family to switch from itâs ancestral to itâs descendant function.
Incidentally his whole argument is pointless because the reference you brought can only support the inference that 3 mutations are required for the functional âswitchâ in question if the phylogenetic history it is based on actually occurred. If it occurred, calculating itâs prior probability after the fact as if whatever number you obtain somehow constitutes a falsification of history is an exercise in insanity.
Yeah thatâs still too vague to be meaningful. How different must one binding site be from another to be ânewâ? Let me help you: If itâs at all different, itâs new. No matter how small a degree, if it is in any way different, itâs new. Being different means something that is now the case was not previously the case, and hence itâs new. So any mutation to a protein produces something new. If this results in the ability to bind a different molecule, no matter how similar this different molecule is to the one the protein could bind before, then it is a new binding site.
Would you happen to have any reference that supports your claim that to evolve such a ânew binding siteâ requires 3 or more specific mutations?
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So do you agree that a single mutation can suffice to bring about a novel function within a short time (it took about two weeks in that paper)?
You are assuming all combinations of the four amino acids (not bases) are equiprobable. They are not. These makes the above claim irrelevant. In fact, if you had bothered to read this part of the paper, you wouldnât have brought up this irrelevant objection:
More juicy details on mutational steps which you love to banter about:
In summary, your objections are demolished although they had no basis to begin with.
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ok, but it does give us a clue about the number of mutations which required to get a new function. and that number should be higher if we are talking about new functions compare to existing functions.
this is all i need to do as the first step. so we now agree that at least few mutations required in order to get a new function?
no. it needs to bind to a different molecule that was not possible before that change. this is very clear definition we cant play with.
isnt this what we have seen above with that (not even new) function?
if this is what we see in the lab sure (even though its just a promoter). at least theoretically.
if this is true then many of the alternative pathways are inaccessible because they require more mutations. so this make that even harder to get a new function.