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80beats
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For Proteins, Evolution Is a One-Way Street

one-wayOrganisms evolve to fit the world around them–but if the changes don’t work out, can a creature reverse the process? Say, for example, an insect originally eats a wide variety of tree leaves, but then evolves to live exclusively on the leaves from one type of tree that is abundant in its habitat; if that tree goes extinct, can the bug reverse course? A new study in Nature sheds some light on such questions, which have perplexed evolutionary biologists for many decades.

More than a century ago, the French–born Belgian palaeontologist Louis Dollo proposed that evolution cannot retrace its steps to restore a lost trait — an idea that has remained controversial [Nature News]. So researchers set out to test “Dollo’s Law” on the molecular level, studying a protein called the glucocorticoid receptor, which binds to the hormone cortisol to regulate the stress response. Study coauthor Joseph Thornton says that at least in this protein’s case, new mutations make it practically impossible for evolution to reverse direction. “They burn the bridge that evolution just crossed” [The New York Times], he says.

Researchers already knew that 440 million years ago an early version of the glucocorticoid receptor was able to grab hold of a variety of hormones, and attached itself only weakly to cortisol. Over the next 40 million years, the receptor evolved through changes to its component amino acids. The receptor had 37 amino-acid alterations, but researchers identified just seven of those as crucial to its switch to cortisol exclusivity–two changes made it more sensitive to cortisol, and five others prevented it from binding to other hormones.

So Thornton’s team reversed those seven changes, and checked to see if the receptor would now function as its ancestor did, and bind to a number of hormones. “We expected to get the ancestral function back out of it,” Thornton said…. “But instead we got a dead protein. It didn’t work at all. It was completely non-functional” [LiveScience].

A close look revealed that five other amino acid changes were preventing the reengineered receptor from functioning. These mutations, which occurred after the protein evolved its new function to bind to cortisol, would cause structural clashes within the protein if it were returned to its ancestral state [New Scientist]. When Thornton’s team reversed these five changes as well, the receptor behaved like its ancestor and attached itself to various hormones.

So here’s the rub: Before the seven key changes could be reversed, the five changes that modified the receptor’s structure would have to be undone. But those five mutations had little effect on how the receptor grabbed hormones. So there was no way that natural selection could favor individuals with reversed mutations [Discover blogger Carl Zimmer in The New York Times]. While the receptor could theoretically make a series of entirely new changes to its structure, taking a new path that would allow it to bind to various hormones, there was simply no going back the way it came.

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Image: flickr / dogbomb

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September 29th, 2009 2:09 PM Tags: evolution, hormones
by Eliza Strickland in Feature, Living World | 3 comments | RSS feed | Trackback >

3 Responses to “For Proteins, Evolution Is a One-Way Street”

  1. 1.   YouRang Says:
    September 30th, 2009 at 10:38 am

    Hmm. They don’t seem to have tried going just part way back to see if there is any difference in those 5 non-functioning sites. I.e. maybe there is no evolutionary drive to change those 5 at the present configuration ; but what would happen if they had changed just 1 and then returned some of the 5, then just 2 then just 3 … of the 7 crucial changes? Maybe there would have been evolutionary advantages for the 5 to go back tat those points. And, the question remains: At how many returned functional amino acids would you get a dead protein? And hence, (call that number N) if you had just changed N-1 proteins, would there have been an evolutionary advantage?

  2. 2.   Fat kid Says:
    September 30th, 2009 at 1:18 pm

    Think of adaptation as a ripple instead of a line. Ennervation broadcasts outward in all directions, not just up or down.

  3. 3.   Enrique Rewald Says:
    January 19th, 2012 at 9:48 am

    Can an evolutionary process become reversed? No doubt that “Dollo’s Law” at the molecular level requires renewal. Accordingly, the stock of a given protein depends on suitable feedback. When lacking, it is to suppose that the particular function cannot be maintained – thus, a ‘two way street’ is to consider as part of evolution. In other words, survival in overcrowded urbanizations requires an adaptation that the progress of hygiene failed to assure. Accordingly, a two way evolution cannot be considered out of question, it may depend on proper stimulation.

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