Biological Information and Intelligent Design: evolving new protein folds

Proteins have an amazing ability to fold into new shapes to fit evolutionary needs.
This is a companion discussion topic for the original entry at https://biologos.org/blogs/dennis-venema-letters-to-the-duchess/biological-information-and-intelligent-design-evolving-new-protein-folds
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As always, I’ve available to answer questions or participate in the discussion. Thanks for reading.

Also, folks might be interested in listening to a brand-new podcast where Scot McKnight and I talk about our soon-to-be released book, Adam and the Genome. I don’t discuss protein folding in the podcast, but you might find it interesting nonetheless. :slight_smile:

Thanks for an interesting and informative post. I have to admit it sort of makes me anxious to read of protein folding, when my medical training has been more focused on protein folding gone bad in prion diseases!

That’s an interesting case, yes - but one that is thankfully rare!

@DennisVenema, my jaw slackened as I read about how much we actually know and understand regarding protein folds, and tracking down the origins of different sections of genetic molecules.

It was quite exciting material … but I can’t imagine some YECs being able to take it seriously … since it is well beyond the usual level of discussion:

“What do you mean, George? How could the fossils of Whales and marine dinosaurs have Any connection to proving Evolution?”

Thanks for this informative series, I am learning a lot and most of it is not going over my head. I think the weakest part of the ID argument is the lack of a well-defined mechanism and maybe this will be in one of your future posts. You explained exactly how the ARHGAP11B gene came to exist in certain Hominids but not others through the evolutionary process. What is the ID explanation? Did a Designer come down and start tinkering at certain times to ensure brain size increased? The biggest puzzle for me is that most ID advocates are not YEC so the Designer must have been flipping switches many times over billions of years. How would someone demonstrate that to be the case?

@JES10

I look forward to whether anybody tackles the last part of the quote above. It is my personal opinion, that the most convincing scenario is that God-guided Evolution … which can happen in two ways:

A) God occasionally flips a switch in genetic molecules and/or sending changes in Natural Selection by ecological means - - for example, the Dinosaur-Killing meteor could have been part of a switch “flipped” in another galaxy… or from somewhere in our solar system.

B) Or, God accomplishes all through natural processes … with only the very rarest of “switch fliipping” involved.

I think the biggest question when someone proclaims Intelligent Design is: does he accept any application of Common Descent (which is a short way of saying natural law is capable of speciation) ? or does he Still Oppose the evolutionary concept of speciation … and so only God, through special creation, can create Kinds and Species.

@DennisVenema

Great post. Fantastic. From near the end:

A new protein region, de novo, carrying with it significant new functional information—that arose through readily accessible mutational steps. While we do not yet know the precise shape of this new, composite protein, we know that it is stably folded, given that it is functional. - See more at: Biological Information and Intelligent Design - BioLogos

We do know that the new protein region is functional but I don’t think we know that it is stably folded. If I am not mistaken, there are lots of protein regions known to be – this is such a great phrase – intrinsically disordered. And this characteristic is known to be important for the function of many of those regions. In fact there are numerous tools devoted to predicting whether a domain is intrinsically disordered. IMO, unless the new region of Arhgap11b is known to be folded, we needn’t and shouldn’t say that it is. We certainly should not assume that because it has function, it is folded.

Intrinsically disordered proteins: a 10-year recap

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Thanks for that critique, Steve. I will ask Brad and Jim to edit the post with an edit I send them. I should have recalled intrinsically disordered proteins. Mea culpa.

That said, that throws a new loop at the ID folks - if protein domains don’t need to have a stable fold to have a function, then a domain could come under selection even without a stable fold - meaning that their claim that evolution cannot produce new protein domains because folding is rare is even more misguided than it first appears.

Still, I’d cheerfully bet a beverage of your choice that it is folded, but you’re right, it could be intrinsically disordered. :slight_smile:

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Yep! In fact, the fold = function thing has been known to be wrong for almost 20 years. (I actually don’t remember if Meyer or Axe explicitly equate the two.) The first analyses of intrinsically disordered regions (and whole proteins) date to before the turn of the millenium.

One really interesting outcome of studying these kinds of domains is the finding that they sometimes serve as switches, able to adapt their form to different functions. That’s really cool.

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@DennisVenema

Excellent presentation, Dennis.

If I have a problem with it, it is that it is negative, rather than positive.

In my opinion these facts prove God is God of the Facts, not God of the Gaps. Western dualism distinguishes between God and Nature, which is fine, but God created nature and works through nature.

There is no obvious boundary between God and Nature. God is more than the spiritual and Nature is more than the physical.

It is unfortunate that advocates of ID feel that they have to demonstrate the existence of God by showing the “nature” cannot produce evolution. Now it is true that nature if it is random, not rational, could not produce evolution, but nature is not random, although it has some random aspects, and is rational, so it can and does produce evolution, because it is designed and guided by God.

Its rationality is amply demonstrated by the existence of the DNA code or language and the way it communicates designs. The fact is that evolution does not disprove the existence of God, it proves that existence of God.

The biosphere declares the Glory of God, DNA proclaims the work of God’s hands.

Those who belittle science are also belittling the work of God. Those who deny that evolution is the work of God are denying the testimony of the Bible that God created the world

Those who support those who attack the truth of science and nature are attacking God’s Truth.

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The description does not appear to be a protein from scratch but a modified enzyme. Am I mistaken here ?

Hi Bill - there are a few nylonases, but the one that is de novo has 392 amino acids. It arose as a frameshift mutation in an unrelated gene. This sequence then is duplicated, and the duplicate has a few amino acid changes that make it a better nylonase. The references lay this all out.

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Hi Dennis
Thanks for the explanation. From scratch you mean from an unrelated gene not from a non functional sequence. I think that Meyer’s argument is building a protein from a non functional sequence since that is what Axe was testing for.

Hi Bill - Meyer’s argument (based on Axe) is that protein folds are too rare for evolution to find. The amino acids in the de-novo nylonase are a new sequence of amino acids - the frameshift mutation means that the old gene is being translated in a different reading frame, hence a new string of amino acids. This new, de novo, protein folds up into a functional nylonase.

If Meyer’s argument was correct, this could not happen. The probability of these new amino acids finding a functional sequence is, according to Meyer, only one in 10 to the 77th power. So, the fact that we can observe new functions coming into being shows that his estimate is grossly over-inflated.

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The nylonase example in the older post, and the Arhgap11b example in this one, are exactly that.

Hi Dennis
I understand and appreciate your point but with all respect since your sequence was part of a functional gene it is not a random sequence. Your explanation does show that from function you can evolve a new adaptive function but is does not support evolving function from non function. We know based on alternative splicing that shortened gene sequences can have function but again they started from function. All that said, I think you have come up with an impressive challenge.

Hi Bill - you’re making an argument that is distinct from Meyer’s/Axe’s - which is fine - but I’m responding to Meyer in this post. Meyer’s argument is not that random sequences cannot become new protein folds - it is that protein folds are so rare that evolution cannot find them. Nylonase is a new protein fold. It has no amino acid/fold relationship to the protein that came before it because it is in an alternative reading frame. Do you understand what different reading frames are for a sequence?

Also, how about the example in this post? It’s a new protein domain, with a function, that comes from a previously non-coding sequence. Is that enough of a “new function from non-function” for you?

Just so everyone can see what Meyer’s argument actually is, here’s a quote from Darwin’s Doubt (pg 207). Note that Meyer is specifically arguing that you cannot convert an existing gene into one with a new fold or function:

“… Axe’s later experiments establishing the extreme rarity of protein folds in sequence space also show why random changes to existing genes inevitably efface or destroy function before they generate fundamentally new folds or functions… If only one out of every 10^77 of the alternate sequences are functional, an evolving gene will inevitably wander down an evolutionary dead-end long before it can ever become a gene capable of producing a new protein fold. The extreme rarity of protein folds also entails their functional isolation from each other in sequence space.”

I agree that you have shown a strong counter argument to Meyer’s claim here.

The bigger question is the Cambrian was the transition from single cell to multi cell. That is a big jump in complexity requiring many new interactive proteins such as the home box group. Also the sudden appearance of central control nervous system, muscular system, and respiratory systems.

I think I understand the frame shift and that it can disrupt the AA order. Since there is redundancy in condon codes I believe we can’t understand the magnitude of the disruption until we look at the change in the AA sequence.

I think the experiment you cited is very interesting and I would like to understand the details of how novel function evolved. Thanks for the great post.

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