In today’s Nature, we find this article:
“Synonymous mutations in representative yeast genes are mostly strongly non-neutral.”
They investigated what effect “synonymous, nonsynonymous and nonsense” mutations involving “21 endogenous genes” would have on yeast. The fitness levels of synonymous and nonsynonymous fell in equal (though not ‘identical’) measure–around 75%.
I don’t have access to the article itself, only the abstract. The abstract begins thusly:
Synonymous mutations in protein-coding genes do not alter protein sequences and are thus generally presumed to be neutral or nearly neutral[1,2,3,4,5]
1 through 5 are citations. Who are they: Kimura, King and Jukes, Nei and Kumar, Li and Dan Graur. The heavyweights of neutral theory.
The abstract ends:
The strong non-neutrality of most synonymous mutations, if it holds true for other genes and in other organisms, would require re-examination of numerous biological conclusions about mutation, selection, effective population size, divergence time and disease mechanisms that rely on the assumption that synonymous mutations are neutral.
In the Phys.Org press release, one of the authors is quoted saying:
“Since the genetic code was solved in the 1960s, synonymous mutations have been generally thought to be benign. We now show that this belief is false,” said study senior author Jianzhi “George” Zhang, the Marshall W. Nirenberg Collegiate Professor in the U-M Department of Ecology and Evolutionary Biology.
“Because many biological conclusions rely on the presumption that synonymous mutations are neutral, its invalidation has broad implications. For example, synonymous mutations are generally ignored in the study of disease-causing mutations, but they might be an underappreciated and common mechanism.”
I can hardly wait to see what Larry Moran says at his Sandwalk blog.
I have often made fun of those who hold to the Neutral Theory in the non–Kimuran sense. My problem with the idea of everything being ‘neutral’ was that, hypothetically, anything can become anything. There’s no start nor finish to this process. I thought it was extravagant; instead, it was just wrong. Modern techniques–the use of Crisper to make mutant genes, has now allowed us to see how NT is a ‘dead-end.’ We can only hope that evolutionary biologists can see this. But there’s really no reason for such hope, is there?
The authors tell us that there’s no reason to believe that what they found in yeast won’t be found in other eukaryotic species, but that this will have to be tested to confirm that this ‘dead-end’ generally holds. I’ll bet on it holding in most families with few, if any, exceptions. We’ll see. Science progresses (while Darwinism ebbs).
Moran will just blow this off like he did the ENCODE results which found widespread functionality across the genome.
Of related note:
From a 2014 Cell paper:
Synonymous Mutations Frequently Act as Driver Mutations in Human Cancers
Here, in an analysis of >3,000 cancer exomes and >300 cancer genomes, we present robust statistical evidence that this is indeed the case: that synonymous mutations must frequently contribute to cancer. These silent mutations in exons may act through diverse molecular mechanisms, and they are often associated with changes in splicing.
The DOI is Open Archive: 10.1016/j.cell.2014.01.051
I think it is more possible that Professor Moran will ignore it.
Under the heading of “Silent Mutations and Neutral Theory”, he wrote, “Neutral Theory and random genetic drift explains variation and it also explains molecular evolution and the (approximate) molecular clock. There are no other explanations that make sense and nobody has offered a competing explanation since Motoo Kimura (1968) or Jack King and Thomas Jukes (1969) published their papers almost fifty years ago.”
It’s difficult to crab back from such a positive statement.
To add a little background information to this, it is interesting to note that neutral theory effectively falsified natural selection as a major player in evolution.
As Moran himself quoted Austin Hughs as saying, ‘Darwinism asserts that natural selection is the driving force of evolutionary change. It is the claim of the neutral theory, on the other hand, that the majority of evolutionary change is due to chance.’
Even Richard Dawkins himself finds the claim that chance alone, all by its lonesome, can explain life to be “absolutely inconceivable”.
In the following video Richard Dawkins states that, “it cannot come about by chance. It’s absolutely inconceivable that you could get anything as complicated or well designed as a modern bird or a human or a hedgehog coming about by chance.’
To put it even more bluntly than Richard Dawkins did, Jay Homnick states, “Once you allow the intellect to consider that an elaborate organism with trillions of microscopic interactive components can be an accident… you have essentially “lost your mind.”
Thus, with Natural selection being tossed to the wayside by population genetics via ‘neutral theory’, as the supposed explanation for the ‘well designed’ things we see in life, Evolutionists, such as Moran, did not accept such a devastating finding as an outright falsification for their theory, as they should have done, but instead are now reduced to arguing that the ‘well designed’ things we see in life are, basically, the result of pure chance with natural selection now playing a very negligible role if any role at all.
Contrary to what proponents of neutral theory may want to ‘religiously’ believe to the contrary, with natural selection out of the way as the supposed ‘designer substitute’,,,
,,, with natural selection cast to the wayside as the supposed ‘designer substitute’, then the explanation for that ‘appearance of design’ in life does not default to chance, all by its lonesome, as the supposed explanation for the ‘wondrous diversity’ of life, (as Evolutionists such as Moran want to hold), but instead the explanation reverts back to the original intuitive assumption that the ‘wondrous diversity’ and complexity of life must be designed,
As Richard Sternberg states, “Darwinism provided an explanation for the appearance of design, and argued that there is no Designer — or, if you will, the designer is natural selection. If that’s out of the way — if that (natural selection) just does not explain the evidence — then the flip side of that is, well, things appear designed because they are designed.”
Of supplemental note to ‘the death of neutral theory’:
Goodness me, I’m feeling faint. I have to admit I’m in agreement with PAV, Bornagain77, Richard Dawkins and Darwinism and in disagreement with Austin Hughs (who he?) if BA’s quote is correct:
There can be no adaptive change without selection.
Fred Hickson still doesn’t understand that natural selection is a process of ELIMINATION.
DaveScot provided an article that says synonymous mutations cause problems due to timing issues. It seems cells do NOT have an equal mix of tRNAs. So, if the tRNA that is replacing another is rare, it causes issues with the timing and the protein doesn’t fold properly. This is also in the book the “Design of Life” Dembski and Wells. So, yes, we have known that those mutations aren’t always neutral for years.
FH, but the point is that Moran and company ARE correct about the inadequacy of Natural Selection.
i.e. Natural Selection IS found, via population genetics, to be grossly inadequate as the supposed ‘designer substitute’.
For instance, the ‘waiting time problem’,
Moreover, it doesn’t take a PhD in mathematics to understand why Natural Selection is grossly inadequate as the supposed ‘designer substitute’.
In order to explain the ‘appearance of design’ we see in life, Natural Selection would have to operate at the molecular/genetic level.
Yet, Natural Selection cannot possibly operate at the genetic level but can only select at the whole organism level.
This presents an insurmountable problem for Darwinists.
This insurmountable problem for Darwinists is clearly illustrated, and easily understood, with what is termed the ‘Princess and the Pea’ paradox.
Dr. John Sanford goes over the easy to understand “Princess and the Pea” paradox in the following video at the 8:14 minute mark:
The easy to understand lesson of the “Princess and the Pea” paradox is that Natural Selection can only select for an entire organism and cannot possibly ‘see’, and/or select for, individual nucleotides that are buried underneath the many layers of mattresses that selection, i.e. the Princess, is sleeping on.
The term “non-neutral” is the nice way to say “harmful”. Or even more, “strongly harmful” – and therefore damaging to evolutionary claims that they’re just neutral.
Synonymous mutations are part of the “niche” that the organism has to fight against in order to survive.
BA77:
Very nice post @5. Lays things out clearly and dramatically.
Let’s not forget that this article is published in the journal Nature. Nature is for the most part, or has been, the enforcer of Darwinian orthodoxy and so here is an article that explodes a rival to Darwinian thought–as Fred Hickson wants to point out. Now the problem with this is that without Neutral Theory, Darwinism is dead!!
How can that be? How can I make such a statement? Easy. The whole reason that the Neutral Theory came into existence were a set of experiments utilizing gel electrophoresis–cutting-edge technology in the late 60’s, that demonstrated that contrary to neo-Darwinian orthodoxy, there was an incredible level of genetic polymorphism. This meant that organisms would necessarily have to be “purifying” countless alleles and with each allele needing correction countless numbers of the species would have to die, termed ‘genetic load.’ This came from Haldane’s calculations done in the 50’s. Faced with this dilemma, Motoo Kimura developed his Neutral Theory, a theory that was at once opposed by neo-Darwinists. That was over 50 years ago.
Summing up, the neutral theory was meant to “save” Darwinian orthodoxy and, so, with the seeming “death of the neutral theory” now being spotlighted by Nature, the unintended consequence (something that seems to have been forgotten about) is that neo-Darwinism falls flat. It fails as an explanatory theory.
It’s almost like Nature took a shot at the Neutral Theory and then was killed by the ricochet. Interesting times.
PaV, “It’s almost like Nature took a shot at the Neutral Theory and then was killed by the ricochet.”
🙂 🙂
LOL
SA states:
The terminology isn’t that important. Neutral Theory always acknowledged that the bulk of mutations could be deleterious. One could argue persuasively that this finding, if it holds, bolsters the role of NS since NS is very efficient at stripping out deleterious mutations at the phenotypic level before they become fixed at the molecular level.
Try as it might, ID just can’t seem to get that stake through the heart of NS.
CD
Or is it that “try as they may, evolutionists cannot get a theory that works”?
Aside from the fact that strongly harmful mutations will cause a higher mortality rate, this still won’t help increase the number of beneficial mutations needed in the time required.
At least they have a theory. Science has always been about trial and error. Beats “design, a/k/a God, did it.”
CD at 14,
Aliens did it? Who created the aliens? They are accidents too?
CD: “Try as it might, ID just can’t seem to get that stake through the heart of NS.”
Yet, seeing that NS is not even defined in a rigorous, i.e. ‘scientific’, manner, then, getting a ‘stake through the heart of NS’ is very similar to trying to nail Jello to the wall.
As Professor of Zoology John O. Reiss himself honestly admitted, “The rigor of this approach, however, is lessened because there is as yet no universally agreed upon measure of fitness; fitness is either defined metaphorically, or defined only relative to the particular model or system used. It is fair to say that due to this lack, there is still no real agreement on what exactly the process of natural selection is. This is clearly a problem.”
i.e. As the late Stephen Jay Gould himself once honestly admitted, NS functions far more in the realm of fantasy, i.e. of imaginary just-so story telling, than it functions in the realm of real empirical science.
CD @14
If there’s evidence for design, then that beats trial and error without it.
CD: . “One could argue persuasively that this finding, if it holds, bolsters the role of NS since NS is very efficient at stripping out deleterious mutations at the phenotypic level before they become fixed at the molecular level.”
Yet the real world is not nearly as kind to CD’s imaginary speculations as he hopes it to be.
Perhaps I don’t understand all the terminology, but it seems to me that this discussion conflates two different types of “Neutral Theory”
– one type says that synonymous codons that call for the same amino acid in a protein are neutral;
i.e. the same protein results with either codon.
– the other says that most mutations in a gene are neutral vis-a-vis natural selection;
i.e. changing some amino acids at random has little effect on the protein function and hence,
the survival (or reproductive success) of the organism.
While these two may be related, they are not the same thing. The article in question appears to be about the first type (synonymous codons), while much of the subsequent discussion is about the second type (neutral evolution).
Please correct me if I’m wrong.
BA77:
Excellent posts BA77. Very illuminating of the topic of this thread.
Fasteddious:
Your number (1) is the same as your number (2). Neutral mutations–synonymous substitutions–occur that leave the function of the protein unchanged (apparently), and thusly, NS is unable to “see” these different forms. This solves Kimura’s problem from the late 60’s of so many polymorphic amino acid sites in the genome, each needing preferential ‘death’ of organisms within that species–which, of course, is unsustainable. Hence Kimura’s Neutral Theory.
Here, discovered only because of modern laboratory techniques that enable gene modification via the use of Crisper, the authors show that while on the surface these polymorphic versions of proteins don’t seem to matter, they do indeed matter and cause a loss of fitness to the organism. So, they’re NOT neutral. NS can “see” them.
Chuckdarwin@12:
But that’s what I’ve pointed out: that the journal, Nature, the historical guardian of NS and hence neo-Darwinism, is very glad to present an article that seems to shoot down what is being said by biologists who hold to the
But when you say that “Neutral Theory always acknowledged that the bulk of mutations could be deleterious,” I think you’re just making it up. Otherwise, you have neutral theorists holding onto an obvious contradiction: “we say that most mutations are neutral; that is, NS doesn’t see them. But, of course, they could always really be ‘deleterious.’ You can’t have your cake and eat it too. How about some intellectual honesty.
CD@14:
You’re setting up a false dichotomy here: either there is a completely ‘material’ cause for what we see in the fossil record, OR, “God did it” and there’s no more to be said about it.
Who was Gregor Mendel? He was a priest, a canon in Switzerland. He was a man of God. Yet it is from him that comes the only true law at work in biology that we know of: Mendelian genetics.
Did he say: “Oh, the reason that so many species exist is that God made each and every one of them.”? No, he used “trial and error” to determine that variation of traits exist contemporaneously in each population.
Likewise, today’s scientist has simply to say: “Biological diversity is the result of some kind of intelligent design. How can I discover the rules of this intelligence.” And then you use “trail and error” to get at these rules.
The history of science is littered with men (and women) who came up with ideas that proved pivotal and they did so by simply asking the question: How might God have done this?
Here’s Darwinism (basically Fisher’s ‘Fundamental Theorem of Natural Selection’): the rate of increase in fitness is inversely proportional to the rate of death. And on this, we build the entirety of biological diversity? Really? Does the fossil record support such a contention? Not even Darwin thought so.
PaV/21 claims:
Really, PaV?
PaV/21
Having a problem with the Nature link, hopefully this works: https://www.nature.com/scitable/topicpage/neutral-theory-the-null-hypothesis-of-molecular-839/
Chuchdarwin/23:
These quotes come from the section of the link you quoted from.
Right before the quote:
Right after the quote:
Your quoted section simply lays out the “dispute” that still exists today. The “observations . . . widely confirmed with . . . genomic data . . . are consistent with the neutral theory but contradict selectionist theory. There are two sides to this debate. Nature has taken one side.
But, as you can see from another quote taken from the very beginning of your link, neutral theory “contradicts” selectionist theory–that is, that NS “selects” variations that arise.
By the way, @21 , I wasn’t trying to imply that you were being dishonest. I thought rather that the “making things up” had to do with just not knowing where the “dispute” actually stood. 🙂
PaV/24
I appreciate your explanation that you weren’t implying that I’m simply pulling stuff out of thin air. I’ve been called a lot of names on this blog, but irrespective of that, I think I’ve been diligent at sourcing my comments.