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Posted by on Feb 16, 2014 in Evolution, featured, Research, Science | 11 comments

Evolution of Associated Proteins

This is for my various creationist readers who keep (mistakenly) proclaiming that multi-protein systems can’t evolve. I’ve shown why this isn’t true, but it’s time for another one. Again, this paper directly refutes those claims and shows that evolution CAN result in multi-protein systems.

Two of the authors (but not the lead author) are people that are familiar to those in the community; Sean M. Carrol and Joseph W. Thorton. The paper’s lead author is Jamie T. Bridgham and it is titled Evolution of Hormone-Receptor Complexity by Molecular Exploitation.*

So, the abstract opens with the same complain that creationists have.

According to Darwinian theory, complexity evolves by a stepwise process of elaboration and optimization under natural selection. Biological systems composed of tightly integrated parts seem to challenge this view, because it is not obvious how any element’s function can be selected for unless the partners with which it interacts are already present.

So, unlike creationists, these three sat down and did some science and came up with an answer to the question. I’d like to point out that this research paper was published in 2006. Since it doesn’t say “We discover how tightly integrated biological system evolved”, then it’s easy to see how creationists miss this. Whenever you hear this argument, give them a link to this paper and then enjoy the change in subject.

A particular steroid hormone (aldosterone) and it’s specific receptor partner (MR) were examined. MR and the related GR were formed from a gene duplication way back in the ancestor of vertebrates. GR is activated by cortisol (a stress hormone) to regulate metabolism and inflammation. MR is activated by aldosterone and controls some aspects of homeostasis.

While MR can be activated by cortisol, it doesn’t happen often because of some other biochemical effects. The question is, how did MR develop such a tight affinity for aldosterone? To quote the authors (and every creationist)

If the hormone is not yet present, how can selection drive the receptor’s affinity for it? Conversely, without the receptor, what selection pressure could guide the evolution of the ligand?

The authors looked for the ancestral form of the MR/GR common ancestor.  The fact that this can be done in a statistically robust fashion is proof enough of common ancestry. They identified a corticoid receptor in jawless fishes (the most primitive** organism to not have GR and MR) and both GR and MR in skates. This data helped determine that the GR/MR split occurred more than 450 million years ago.

They recreated this primitive protein that they called the ancestral corticoid receptor (AncCR). They found it was very sensitive to aldosterone, but also activated by low doses of cortisol. Let me add that this also isn’t just a flight of fancy, but highly statistically robust. If you get to arguing with a creationist and they aren’t talking about statistical data, then they don’t have any idea how this work is done and therefore are not in any position to criticize it.

Interestingly, the authors thought that they were looking for how MR became associated with alodsterone, but what they found was that aldosterone affinity was the original considition and corticoid affinitiy came later. This is doubly interesting because only tetrapods produce aldosterone. So, the ability to bind with aldosterone appeared much sooner than aldosterone itself did.

So, that sort of punches a hole in the problem right there. It is perfectly plausible that this happened with other protein systems. Just because a protein does a certain thing doesn’t mean that it only does that thing.

The authors then started looking at how to get from the ancestral protein to the modern protein. The GR obviously lost the ability to bind with aldosterone. By mutating the ancestral form, they found a version that increased it’s inability to bind with aldosterone by three orders of magnitude and was still able to moderately bind with cortisol. This occurred due to two changes in the protein.

An analysis of the human GR shows that it is these two changes that exist in our own system. So, what the researchers did was create an ancestral protein, try to mutate it so it had the same effect as the modern protein, then compared that to the actual modern protein. 

This is a huge vindication for evolution. Not only does it work, but it has predictive power.

Our findings demonstrate that the MR-aldosterone partnership evolved in a stepwise fashion consistent with Darwinian theory, but the functions being selected for changed over time. AncCR_s sensitivity to aldosterone was present before the hormone, a by-product of selective constraints on the receptor for activation by its native ligand. AncCR and its descendant genes were structurally preadapted for activation by aldosterone when that hormone evolved millions of years later. After the duplication that produced GR and MR, only two substitutions in the GR lineage were required to yield two receptors with
distinct hormone-response profiles. The evolution of an MR that could be independently regulated by aldosterone enabled a more specific endocrine response, because it allowed electrolyte homeostasis to be controlled without also triggering the GR stress response, and vice versa.

This picture shows the results very clearly.

GR_MR

 

The ancestral state (AncCR; in black) could slightly bind with aldosterone. There was a gen duplication event somewhere in the 470-440 million years ago range. Both genes (in blue) built proteins that could bind with aldosterone. Then, somewhere between 440-420 million years ago, the GR version lost the ability to bind with aldosterone.

Of course, to this point, aldosterone didn’t even exist. The earliest tetrapods existed about 395 million years ago, so the appearance of aldosterone occurred somewhen between then and 420 million years ago.

While the MR/aldosterone system may look complex and one wonders how could the protein evolve before it could do anything and how could the receptor evolve before there was anything to receive, the conclusion is radically more simple.

The receptor had the ability long before the protein it binds to existed. And this is because, proteins (unlike the vast majority of designed things that we know of) can do multiple things like binding with multiple targets.

They didn’t have to evolve together. This research shows, quite clearly, that the one evolved tens of millions of years before the other.

 

_________________________________

*Bridgham, J., Carroll, S. & Thornton, J. Evolution of hormone-receptor complexity by molecular exploitation. Science (New York, N.Y.) 312, 97–101 (2006).

** I use primitive in the evolutionary sense.

  • gil

    this paper already have been critique by prof michael behe here:

    http://www.discovery.org/a/3415

    “The bottom line of the study is this: the authors started with a protein which already had the ability to strongly interact with three kinds of steroid hormones (aldosterone, cortisol, and “DOC” [11-deoxycorticosterone]). After introducing several simple mutations the protein interacted much more weakly with all of those steroids. In other words, a pre-existing ability was decreased.

    • SmilodonsRetreat

      Umm… and therefore Behe agrees that the paper does exactly what I say that it does. That is, render the complain about complex structures moot.

      This, gil, is called a ‘goal post shift’ in case you weren’t aware. You’ll note, if you read the paper and my report again, that none of us are talking any decrease or increase in affinity. It is specifically about how complex interactions formed in biology, which I noted and which the paper noted. And which you are now ignoring.

      It is so damned frustrating arguing with you people (creationists). You refuse to put up any evidence of your own and when science puts up evidence, then it is totally rejected by tricks of logic… not by any scientific reasons.

      • gil

        this is not complex system at all. 2-3 mutations its nothing. like i show before: we can test this this way- lets say that we have a self replicat car or any other complex system. can this system evolve into another complex system step wise? according to the evolution the answer is yes. id claims its not. can you show that its possible?

        • SmilodonsRetreat

          I just did. There are two proteins. One is the receptor of the other. This is, by definition, a complex system.

          The fact that the receptor evolved much, much earlier than the steroid is immaterial.

          In fact, this shows that a complex system CAN evolve and DID evolve.

          YOUR problem is that the two proteins didn’t evolve together. Only creationists have ever had this as a requirement. It’s not. You don’t like it because it shows something you don’t want to see.

          And the number of mutations??!!? Talk about a red herring. It doesn’t matter because those two mutations not only didn’t destroy the functioning of the system, but actually enhanced it. And that enhancement happened with just two or three mutations. Which totally destroys all the complaints that creationists have about mutations too.

          Tell you what. In the spirit of cooperation though, you tell me how this system came about with equivalent evidence as shown in this paper.

          • gil

            no. homologus protein is veru similat to another protein. its not the case with systems with diferent function and stucture. again- can you as intellegent designer change a cell-phone into watch?

          • SmilodonsRetreat

            Cell phones and watches are NOT self-reproducing organisms that have mutations and breeding populations.

            Why can’t you creationists understand this? Ever since William Paley said his famous watchmaker analogy, you guys cannot get it through your biases that there is a fundamental difference between the intelligently designed devices of humans (and other animals) and the living things themselves.

          • gil

            let me put this this way- can a self replicat cell phone change into watch?

          • SmilodonsRetreat

            My cell phone has more feature than any watch I’ve ever owned did.

            Here: https://www.youtube.com/watch?v=mcAq9bmCeR0

            Evolution of a clock.

          • gil

            yes. i mean a self replicat digital watch into cell-phone(more complex without with new function). or even a cell-phone from a self replicat material. it is possible?

  • Pingback: Most Mutations are Harmful | Smilodon's Retreat()

  • l zoltan

    what goal post shift? The goal is macro evolution or creating complex molecular machines that are found in the cell or like bacterial flagellum

    M. Behe:

    Much worse, Miller is as subtly misleading when writing about the substantive points ofThe Edge of Evolution as he is when making supercilious offhand comments. Miller writes: “Telling his readers that the production of so much as a single new protein-to-protein binding site is ‘beyond the edge of evolution’, [Behe] proclaims darwinian evolution to be a hopeless failure.” But the book says plainly that it is two, not one, binding sites that marks the edge of evolution. That was not an obscure point. Chapter 7 is entitled “The Two-Binding-Sites Rule”; Figure 7.4 has a line at two binding sites, with a big arrow pointing to it labeled “Tentative molecular edge of evolution.” What’s more, the book goes out of its way to say that Darwinism is certainly not a “hopeless failure”, that there are important biological features it clearly can explain. That’s why one chapter is called “What Darwinism Can Do”.

    Speaking of throwing around irrelevant references, Miller writes:

    “Telling his readers that the production of so much as a single new protein-to-protein binding site is “beyond the edge of evolution”, [Behe] proclaims darwinian evolution to be a hopeless failure. Apparently he has not followed recent studies exploring the evolution of hormone-receptor complexes by sequential mutations (Science 312, 97-101; 2006), the ‘evolvability’ of new functions in existing proteins — studies on serum paraxonase (PON1) traced the evolution of several new catalytic functions (Nature Genet. 37, 73-76; 2005) — or the modular evolution of cellular signalling circuitry (Annu. Rev. Biochem. 75, 655-680; 2006).”

    Now, dear reader, when Miller writes of “protein-to-protein” binding sites in one sentence, wouldn’t you expect the papers he cites in the next sentence would be about protein-to-protein binding sites? Well — although the casual reader wouldn’t be able to tell — they aren’t. None of the papers Miller cites involves protein-protein binding sites. The Sciencepaper concerns protein-steroid-hormone binding; the Nature Genetics paper deals with the enzyme activity of single proteins; and the Annual Reviews paper discusses rearrangement of pre-existing protein binding domains. What’s more, none of the papers deals with evolution in nature. They all concern laboratory studies where very intelligent investigators purposely re-arrange, manipulate, and engineer isolated genes (not whole cells or organisms) to achieve their own goals. Although such studies can be very valuable, they tell us little about how a putatively blind, random evolutionary process might proceed in unaided nature.

    Miller’s snide comment, that apparently I haven’t followed these developments, seems pretty silly, since it’s so easy to find out that I followed them closely. You’d think he should have noticed that I cited the Annual Reviews article in The Edge of Evolution in Appendix D, which deals in detail with Wendell Lim’s interesting work on domain swapping. You’d think he easily might have checked and seen that I was quoted in the New York Times commenting on Joseph Thornton’s Science paper when it first came out a year ago. You’d also think he’d then have to tell readers of the review why I thought the papers weren’t pertinent. You’d be thinking wrong.

    Much worse, Miller is as subtly misleading when writing about the substantive points ofThe Edge of Evolution as he is when making supercilious offhand comments. Miller writes: “Telling his readers that the production of so much as a single new protein-to-protein binding site is ‘beyond the edge of evolution’, [Behe] proclaims darwinian evolution to be a hopeless failure.” But the book says plainly that it is two, not one, binding sites that marks the edge of evolution. That was not an obscure point. Chapter 7 is entitled “The Two-Binding-Sites Rule”; Figure 7.4 has a line at two binding sites, with a big arrow pointing to it labeled “Tentative molecular edge of evolution.” What’s more, the book goes out of its way to say that Darwinism is certainly not a “hopeless failure”, that there are important biological features it clearly can explain. That’s why one chapter is called “What Darwinism Can Do”.

    Regrettably, that’s Miller’s own special style. He doesn’t just sneer and thump his chest, as some other Darwinists do. He uses less savory tactics, too. His tactics include ignoring distinctions the author draws (cellular protein-protein binding sites vs. other kinds of binding sites), mischaracterizing an argument by skewing or exaggerating its claims (“so much as a single …”), and employing inflammatory, absolutist language (“[Behe] proclaims darwinian evolution to be a hopeless failure”). He turns the principle of charitable reading on its head. Instead of giving a text its best interpretation, he gives it the worst he can.

    • SmilodonsRetreat

      The challenge for you and Behe remains the same. Calculate CSI for any organism or system. What values indicate design? What values indicate non-design? Why?

      What is the difference in values between random, design, and evolution? Why?

      You guys can argue quotes all day long, but no one cares. Until ID proponents step up and actually do something with their notion (not attacking evolution), then it’s useless.

      And the process covered in the paper simply shows that irreducible complexity is anything but.