Joe Thornton, the University of Chicago biologist whose work on hormone receptor proteins has been followed closely here1-11, has published a new paper in Nature (“Historical contingency and its biophysical basis in glucocorticoid receptor evolution“). Ann Gauger wrote about it last week. Although Thornton himself (pictured at right) always interprets his results in a standard Darwinian framework, in my view the work strongly confirms that severe problems face even relatively minor Darwinian evolution of proteins.
Here’s some background. Vertebrates have two proteins that bind different-yet-similar steroid hormones. Since the proteins themselves are very similar in sequence and structure, the conventional view holds that an ancestral gene coding for one such protein duplicated, and the second copy underwent random mutation plus natural selection to yield the second protein.
While investigating the proteins over the past decade, Professor Thornton’s laboratory showed that the more modern hormone receptor protein would be quite unlikely to be able to reverse-evolve into the ancestral form by random processes, since it would have to pass through multiple, neutral (that is, mutations which by themselves neither help nor hinder an organism’s survival), unselected changes. They subsequently showed — quite unexpectedly — that the ancestral form itself had to accumulate specific, neutral, unselected, improbable mutations to yield the modern protein.
In prior comments on Thornton’s work I proposed something I dubbed a “Time-Symmetric Dollo’s Law” (TSDL).3, 8 Briefly that means, because natural selection hones a protein to its present job (not to some putative future or past function), it will be very difficult to change a protein’s current function to another one by random mutation plus natural selection.
But there was an unexamined factor that might have complicated Thornton’s work and called the TSDL into question. What if there were a great many potential neutral mutations that could have led to the second protein? The modern protein that occurs in land vertebrates has very particular neutral changes that allowed it to acquire its present function, but perhaps that was an historical accident. Perhaps any of a large number of evolutionary alterations could have done the same job, and the particular changes that occurred historically weren’t all that special.
That’s the question Thornton’s group examined in their current paper. Using clever experimental techniques they tested thousands of possible alternative mutations. The bottom line is that none of them could take the place of the actual, historical, neutral mutations. The paper’s conclusion is that, of the very large number of paths that random evolution could have taken, at best only extremely rare ones could lead to the functional modern protein.
A few thoughts:
- Thornton’s lab does terrific work. His is one of the most careful, thorough, meticulous experimental evolution programs in operation anywhere today.
- The level at which Thornton’s group addresses evolution — at the amino acid residue level, and considering many possible mutations — is the minimum level of detail necessary to draw even moderately firm conclusions about the ability of random-processes-plus-selection to explain life. In nature, evolution occurs at the molecular level of specific, individual mutations, so it is there we must look to evaluate possible evolutionary paths. Studies with less detail can say very little on the topic.
- As good as it is, however, Thornton’s work still does not address many important biological factors that would be critical in the history of life, such as the degree of selective pressure or the effect of other genes on the experimental system. So random evolution could well be much less effective than he has shown. (It can’t be more effective, because the biological factors will depend on the molecular properties he studied. The biological factors will only make it worse.)
- Thornton’s work is the first of its kind. So, since the very first protein studied in sufficient detail is found to encounter severe problems in changing its function by even a modest amount by unguided processes, that strongly suggests proteins in general will, too — not just the particular one he studied. Which is exactly what you’d expect from a “Time-Symmetric Dollo’s Law.”
- Thornton’s approach holds great promise for helping to determine a rigorous edge to random evolution. To the extent that a pre-existing system had to pass through improbable, unselected, or even detrimental states — unguided by natural selection or any other unintelligent factor — to reach a rare new function, then to that extent we can say Darwinian evolution does not explain life.
Thornton himself — apparently a conventional Darwinist, and certainly no sympathizer with intelligent design — does not attribute the protein receptor’s new function to Darwinian processes. Rather, he ascribes it mostly to “historical contingency.” That’s another way of saying “dumb luck.”
The edge of evolution lies where reasonably probable, random mutation-selection runs out of steam and “dumb luck” (or — for those willing to consider it — purposeful design) takes over. Thornton’s work shows that the edge occurs far deeper into life than even I had thought.
(1) “Nature Publishes Paper on the Edge of Evolution,” September 30, 2009.
(2) “Nature Paper Reaches “Edge of Evolution” and Finds Darwinian Processes Lacking,” October 6, 2009.
(3) “Dollo’s Law, the Symmetry of Time, and the Edge of Evolution,” October 12, 2009.
(4) “Piddling Pebbles and Empty Promises: Response to Carl Zimmer and Joseph Thornton,” October 26, 2009.
(5) “Not So Many Pathways: Response to Carl Zimmer and Joseph Thornton,” October 27, 2009.
(6) “Severe Limits to Darwinian Evolution: Response to Carl Zimmer and Joseph Thornton,” October 28, 2009.
(7) “Probability and Controversy: Response to Carl Zimmer and Joseph Thornton,” October 29, 2009.
(8) “Wheel of Fortune: New Work by Thornton’s Group Supports Time-Symmetric Dollo’s Law,” October 5, 2011.
(10) “Hagiography for Nature‘s Faithful,” March 23, 2012.
(11) “Debating the Controversy that Doesn’t Exist,” April 6, 2006.