An evolutionary prediction: “Silent” mutations are not always silent

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In 1988, Purvis et al proposed an interesting hypothesis about silent mutations:

Purvis IJ, Bettany AJ, Santiago TC, Coggins JR, Duncan K, Eason R, Brown AJ. The efficiency of folding of some proteins is increased by controlled rates of translation in vivo. A hypothesis. J Mol Biol. 1987 Jan 20;193(2):413-7.

We propose that the way in which some proteins fold is affected by the rates at which regions of their polypeptide chains are translated in vivo. Furthermore, we suggest that their gene sequences have evolved to control the rate of translational elongation such that the synthesis of defined portions of their polypeptide chains is separated temporally. We stress that many proteins are capable of folding efficiently into their native conformations without the help of differential translation rates. For these proteins the amino acid sequence does indeed contain all the information needed for the polypeptide chain to fold correctly (even in vitro, after denaturation). However, other proteins clearly do not fold efficiently into their native conformation in vitro. We argue that the efficiency of folding of these problematic proteins in vivo may be improved by controlled synthesis of the nascent polypeptide.

Silent mutations are mutations which do not change the amino acid of the protein. Since the genetic code is degenerate, more than one triplet codes for the same amino acid, mutations in the genetic code can have no impact on the amino acid and thus the protein.

In other words, silent mutations should not change the function of the protein and are thus considered to be evolutionary ‘neutral’.

But as Wikipedia explains

However, many organisms are known to exhibit codon usage biases, suggesting that there is selection for the use of particular codons due to translational stability. Silent mutations may also affect splicing, or transcriptional control.

In other words, mutations which appear to be neutral, since they still code for the same amino-acid and thus the same protein, are not always neutral.

The Scientist reported on December 21, 2006 that researchers had found that “Silent” mutations are not always silent” and that “Mutations leading to identical amino acid sequences can change protein folding and function”. While examples of silent mutations not being silent existed in ‘lower animals’, this was the first time that an example was found for mammals.

The study was published in Science Express

Kimchi-Sarfaty C, Mi Oh J, Kim I-W, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM. A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science Express, December 21, 2006.

Compare this with the Scientific Vacuity of ID: How does Intelligent Design explain, let alone predict, this? A ‘silent’ mutation which nevertheless has a significant effect on the efficiency of cancer treatments.

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A publication in 1987 predicted a result that was published in December of 2006. What are some of the future research directions that we can take given these findings? Read More

16 Comments

DaveScot said ID (or something like ID) did predict this. ;)

http://www.uncommondescent.com/archives/1901

That is interesting.

When I was an undergrad, codon biases were discussed along with silent mutations. This included discussing how different codons could affect protein regulation and folding even if they didn’t change the sequence. None of our professors were ID activists, yet we still discussed these things because they are part of evolutionary genetics. (Codon usage is driven by mutation and selection.) Calling the paper a prediction of ID is laughable.

Hey, what a coincidence. I saw this paper when I searched for relative advantages and disadvantages of in vivo vs. in vitro experiments, in relation with Behe’s proposed experiment.

We argue that the efficiency of folding of these problematic proteins in vivo may be improved by controlled synthesis of the nascent polypeptide

Can anyone tell me how nascent polypeptides would help the folding?

Calling the paper a prediction of ID is laughable.

Well, it’s a prediction in the sense that ID predicts everything. The word “Prediction” in the Intelligent Design camp doesn’t mean the same thing as it means in the sciences.

(My comment, just for the record, was submitted before Pigwidgeon’s was visible.)

In fact, these days, to express a protein in, say E.c oli , typically what you do is get the gene synthesized using not the native codons but a set of codons optimized for expression in E. coli . Of course, one would not expect Dave Scot to know this, any more than one would expect him to know any biological fact.

Calling the paper a prediction of ID is laughable.

Like a lot (all?) of the science DaveScot posts about on UD, it’s more of a post-diction (or retro-diction?).

Bob

Calling the paper a prediction of ID is laughable.

Like a lot (all?) of the science DaveScot posts about on UD, it’s more of a post-diction (or retro-diction?).

Bob

Yeah…next they’ll be ‘predicting’ the Sun rose this morning. It’s simply amazing how useful ID is, why last week the Sun rose a whole 7 times, 2008 will follow 2007 and GwOD will be replaced as President. Order will triumph over kaos and Christ is on his way back.

I thought this was old news http://www.youtube.com/watch?v=rX_W[…]&search=

DaveScot said ID (or something like ID) did predict this. ;) http://www.uncommondescent.com/archives/1901

The post that you link to on UD was from Dec 23, and it was not a prediction, it was gloating over the recent news that neutral sites weren’t strictly neutral. PaV mentions something about DaveScot’s prediction of this back in November: “I saw it the other day and have alluded to it on several posts already. But I really like the way you anticipated all of this back in Nov.” But he didn’t provide a link, and I didn’t look for it. Of course, all of this is after evolutionists talked about the non-neutrality of these sites (the video I linked to is dated Oct 27, putting it before DaveScot’s supposed prediction). Additionally, from their perspective, they can’t allow any neutrality in the genome. Neutrality (in junk DNA or silent mutations) means that it should be possible to work-out phylogeny from those sites (and surprise, they support reasonable evolutionary phylogenies). What IDists need is to say that the neutrality is an illusion, and that all the genes were specifically chosen by God. This interpretation would be a step towards frustrating phylogenic analysis (they want to say, “humans and chimps don’t share similar DNA because they’re related - they share it because God wanted it that way; there will be no follow-up questions”.) If these things are truely neutral, there’s either no reason for them to exist (in the case of junk DNA) or all creatures could have the same silent mutations.

Given the events in recent (and not so recent) history, “Evolutionary prediction” seems to be a term very loosely aplied to such a theory. Perhaps the best term would be “Evolutionary speculation”.

Re “Order will triumph over kaos”

With some help from Maxwell Smart of Control…

The post that you link to on UD was from Dec 23, and it was not a prediction,

Try reading more carefully: “DaveScot said ID (or something like ID) did predict this. ;)”, which accurately describes “Also note I’ve blogged in the past about how a design theoretic view predicts things like this.”

Gerard Harbison on 1/2/07 writes:

“In fact, these days, to express a protein in, say E.c oli , typically what you do is get the gene synthesized using not the native codons but a set of codons optimized for expression in E. coli . Of course, one would not expect Dave Scot to know this, any more than one would expect him to know any biological fact.”

DaveScot on 12/24/06 writes:

“Silent mutations effecting protein folding isn’t new. When researchers started sticking eukaryote genes into bacteria in quests to get cheap sources of useful enzymes they found that often the protein products ended up as insoluble inclusion bodies. They were insoluble because they didn’t fold right. The also found that by modifying the gene so its codon usage was more like the host the proteins folded properly. IOW the prokaryote caulk gun (ribosome) is a bit different than the eukaryote in the way it processes redundant codons.”

http://www.uncommondescent.com/arch[…]omment-82377

Care to comment on that, Gerard? Probably not.

“Care to comment on that, Gerard? Probably not.”

Many people have a tendency to assume that if someone is talking real stupid then they may be uninformed. Those not familiar with DS simply assume he must be uninformed – it is more polite to think him ignorant than blatantly dishonest.

Perhaps the entire concept of a “silent mutation” is faulty. And also that the concept of “the same amino acid can be coded by two different codons” is faulty in this sense: While each variant may have the same chemical formula, they could be isomers (different geometric setup– even C6H12O6– a common sugar– exists in several different forms, for example. Why not amino acids, which are far more complex?) Perhaps one codon codes for one isomeric form of an amino acid, and another codes for a different isomeric form of the same amino acid. Let’s check this out. While it may not “prove” ID, it may prove that our understanding of the “genetic code” is so far from complete as to be infantile.…

Shawn Fahrer Wrote:

Perhaps one codon codes for one isomeric form of an amino acid, and another codes for a different isomeric form of the same amino acid.

An interesting idea, but amino acids only come in two isomers (or one in glycine’s case) and only the L-isomers are directly coded for. Those organisms which use D-amino acids synthesize them enzymatically.

If different codons did code for different isomers, there would be virtually no silent mutations, which we know is not the case; some mutations (in coding regions) really do have no noticeable biological effect.

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This page contains a single entry by PvM published on January 2, 2007 5:56 PM.

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