Posted on 08/17/2007 4:44:48 PM PDT by blam
Source: University of Oregon
Released: Mon 13-Aug-2007, 15:00 ET
Scientists Re-trace Evolution Via Ancient Protein
Newswise — Scientists have determined for the first time the atomic structure of an ancient protein, revealing in unprecedented detail how genes evolved their functions.
"Never before have we seen so clearly, so far back in time," said project leader Joe Thornton, an evolutionary biologist at the University of Oregon. "We were able to see the precise mechanisms by which evolution molded a tiny molecular machine at the atomic level, and to reconstruct the order of events by which history unfolded."
The work involving the protein is detailed in a paper appearing online Aug. 16 in Science Express, where the journal Science promotes selected research in advance of regular publication.
A detailed understanding of how proteins – the workhorses of every cell – have evolved has long eluded evolutionary biologists, in large part because ancient proteins have not been available for direct study. So Thornton and Jamie Bridgham, a postdoctoral scientist in his lab, used state-of-the-art computational and molecular techniques to re-create the ancient progenitors of an important human protein.
Thornton then collaborated with University of North Carolina biochemists Eric Ortlund and Matthew Redinbo, who used ultra-high energy X-rays from a stadium-sized Advanced Photon Source at Argonne National Laboratory near Chicago to chart the precise position of each of the 2,000 atoms in the ancient proteins. The groups then worked together to trace how changes in the protein's atomic architecture over millions of years caused it to evolve a crucial new function – uniquely responding to the hormone that regulates stress.
"This is the ultimate level of detail," Thornton said. "We were able to see exactly how evolution tinkered with the ancient structure to produce a new function that is crucial to our own bodies today. Nobody's ever done that before."
The researchers focused on the glucocorticoid receptor (GR), a protein in humans and other vertebrates that allows cells to respond to the hormone cortisol, which regulates the body's stress response. The scientists' goal was to understand the process of evolution behind the GR's ability to specifically interact with cortisol. They used computational techniques and a large database of modern receptor sequences to determine the ancient GR's gene sequence from a time just before and just after its specific relationship with cortisol evolved. The ancient genes – which existed more than 400 million years ago – were then synthesized, expressed, and their structures determined using X-ray crystallography, a state-of-the art technique that allows scientists to see the atomic architecture of a molecule. The project represents the first time the technique has been applied to an ancient protein.
The structures allowed the scientists to identify exactly how the new function evolved. They found that just seven historical mutations, when introduced into the ancestral receptor gene in the lab, recapitulated the evolution of GR's present-day response to cortisol. They were even able to deduce the order in which these changes occurred, because some mutations caused the protein to lose its function entirely if other "permissive" changes, which otherwise had a negligible effect on the protein, were not in place first.
"These permissive mutations are chance events. If they hadn't happened first, then the path to the new function could have become an evolutionary road not taken," Thornton said. "Imagine if evolution could be rewound and set in motion again: a very different set of genes, functions and processes might be the outcome."
The atomic structure revealed exactly how these mutations allowed the new function to evolve. The most radical one remodeled a whole section of the protein, bringing a group of atoms close to the hormone. A second mutation in this repositioned region then created a tight new interaction with cortisol. Other earlier mutations buttressed particular parts of the protein so they could tolerate this eventual remodeling.
"We were able to walk through the evolutionary process from the distant past to the present day," said Ortlund, who is now at Emory University in Atlanta. "Until now, we've always had to look at modern proteins and just guess how they evolved."
The work was funded by multiple grants from the National Institutes of Health and the National Science Foundation, the UNC Lineberger Comprehensive Cancer Center and an Alfred P. Sloan Research Fellowship to Thornton.
I guess that my homily that we disagree didn’t posture well with you. You believe what you will … Jesus will out.
Uh yeah, that’s what I’m wondering, is how do they know for sure that that was the ancient configuration for the protein?
But look at it this way. It took 7 mutations for the protein to interact with cortisol. Calculate the odds of that randomly happening. However, those mutations had to occur in a certain order. Now calculate the odds.
That’s one interaction. Think of all that happen in the body. Now calculate the odds. Now keep adding complexity of higher levels of interacting systems all the way up to the many many thousands of evolved species interacting at the ecosystem level.
Anyone want to calculate those odds? Mr. Spock says, ‘I don’t think so captain.’ Probably more zeros than there are atoms in the universe.
That’s why I don’t like evolutionary theory as it sits right now. The logistics suck.
you have “theories.” The THEORY of Evolution, get it?
I can respect you for your firmly held beliefs.
However I do believe, after a fair bit of investigation, that the evidence we have of historical events conclusively shows that the events in a literal interpretation of Genesis could not possibly have happened.
You missed my point. I have no problem with your religious beliefs.
I only have a problem when folks take those beliefs into the realm of science, and distort science, in order to validate their beliefs.
Its one thing to say that, for example, you believe in a global flood.
It is another thing for someone to say that there was a global flood about 4350 years ago and that it is documented by the presence of the Cambrian explosion, fossils on the tops of mountains, and that all methods of radiometric dating are wrong--and besides, scientists are all wrong anyway and evilutions are just practicing a false religion.
Do you see the difference in these two approaches?
Especially, why would I want to bow to such a disgusting philosophy as the one that the homeless, beggar, slave-agitator Jesus promotes?
Fine. I can live with that. A theory is the highest thing an idea can aspire to in science.
And you have beliefs. Can you live with that?
Big Bang Theory.
Cell theory
Atomic theory
Plate tectonics
Catastrophe theory
Category theory
Chaos theory
Graph theory
Knot theory
Number theory
Probability theory
Set theory
Acoustic theory
Antenna theory
Theory of General relativity
Theory of Special relativity
Quantum field theory
Theory of Gravitation
THEORY - get it?
Or do you believe diseases are caused by supernatural causes? LOL!
And that lightning is just Zeus in a bad mood!
In evolution theology miracles are called mutations. Creationism only requires a single miracle to create man, while the followers of Darwin require billions of miracles.
LOL
I know I'm probably wasting my time but what the heck. Your post is a common example of fallacious probabilistic reasoning because the specification isn't independent. I'll try and explain by analogy although I'll simplify it somewhat.
You have 46 chromosomes, 23 pairs. You got one of each pair from your father and the other from your mother but the contributions are thought to be random. The probability you'd get exactly the set of chromosomes you did from your father is therefore 2-23 and likewise from your mother. The probability of your genome is the square of that or 2-46 or about 10-14 which a little less likely than drawing a royal flush two times in a row. That's pretty damn small isn't it?
The probability of your grandparents producing exactly your genome is the square again or 10-28. Got back two more generations and you're at 10-112. Now creationist are fond of saying that there're only about 1080 protons in the universe and "therefore" anything with a probability of less than 10-80 simply can't happen. You're less probable and yet here you are. Right? Well, let's take that as a given even though you can't possibly actually exist according to the creationists.
The problem is the outcome you're calculating the probability of wasn't specified independently of your knowledge. The correct way to reason about the situation is to ask what is the probability of your great great grandparents having a great great grandchild, not you specifically (because that specification isn't independent) but some great great grandchild. And that's naturally quite a bit higher.
And similarly the right way to think about this mutation sequence is in terms of the universe of potential proteins you might get and how many of them are "interesting" which must be defined independently of your knowledge of the result. Achieving that kind of Independence is hard which is why this kind of "post" probability calculation is generally avoided.
Au contraire. Vous avez raison. Great post.
Instead, he may turn to "systems analysis", or "management". She might adopt the Mommy Track.
Both are in there ~
fossils on the tops of mountainsWeren't they all put there by the Jews, in 1922?
In fact, that age is a tad older than most realize. We had/have a model that would allow us to determine the best place to put a postal retail operation. It was similar to the model McDonald's uses.
The report we are working with is about a computer based model that's been pushed backwards to show that there could have been an ancestral relationship between one gene structure and another to result in a close relationship between that gene and a protein which has been identified with an important biologic process.
They then make a leap of faith and strongly suggest that the specific "changes" they designed are a result of evolution.
And, of course, they could be, or of aliens from outer-space, or simply something written into the structure of the universe (mediated through the other 8 dimensions of existence about which we know near to nothing), or Dr. Yakub, or a demigod of some kind, and so on and so forth.
It's entirely possible the "changes" occurred as part of a longterm process of self-directed self-assembly ~ and there are so terribly many things we don't know about genes that this cannot, in fact, be ruled out.
God could have thought about it too ~ and it'd probably looked just like that ~ to the degree computer models can emulate the Mind of God.
One does hope the modelers don't get too pumped up about this ~ next thing you know they'll be slapping on red arm bands, thrusting their right arms in the air, and demanding that we show correct obeisance to their power and majesty.
But you are strictly talking about replication. Though there are many random outcomes, you have a basic set of rules and mechanisms for replication and the randomness works within those parameters.
It doesn’t deal with gene expression. In otherwards the machine is already built and we know it works, and we are only looking at the probabilities involved with one aspect of it’s functioning i.e. replication.
In evolution you are building the machine and creating the parameters for how it works, and doing it by random mutation. Not only do you have the probabilities involved in replication (in this case getting the right mutations to randomly happen and in the right order) but you have the probabilities of expression, i.e. that all those mutations will express themselves as a working organism.
Maybe I’m looking at it wrong but I see far, far more variables at work in evolution than simple gene replication of two viable genomes, and a far more complex set of probabilities.
No, I'm strictly talking about the form of reasoning you used. But forget about it, I knew from experience it wouldn't get through, I just had a few minutes to post.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.
