From Thornton's Lab, More Strong Experimental Support for a Limit to Darwinian Evolution

Michael Behe June 23, 2014 12:08 PM | Permalink

Joe Thornton, the University of Chicago biologist whose work on hormone receptor proteins has been followed closely here^1-11, 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 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.

NOTES:

(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.

(9) "A Blind Man Carrying a Legless Man Can Safely Cross the Street: Experimentally Confirming the Limits to Darwinian Evolution," January 11, 2012.

(10) "Hagiography for Nature's Faithful," March 23, 2012.

(11) "Debating the Controversy that Doesn't Exist," April 6, 2006.

To paraphrase David Berlinski , imagine one novel, the Quixote, being hand copied repeatedly - and all known classic works of literature in all languages coming from this one novel due to the errors made during transcription. The analogy to evolution and common descent is easy to see, but we would never believe all classic works of literature could be created this way. Ironically it’s actually a more complicated task for the sheer dumb luck of neo-darwinism to create all the novel forms of life - not to mention how the first novel life form even came into being.

…But then neither can Darwinism explain how things come to be for instead of an intelligent designer (which intuitively makes sense) it offers random mistakes filtered by natural selection which is just another layer of randomness (which makes no sense at all). The details of why random mistakes would show up in a useful progression such that tremendously complicated structures get built up are never provided, nor explained, nor quantified in any way that science demands. Nor is it at all clear how each mistake could provide instant benefits even though a fully functional transformation remains in the distant future.
…But wait— it gets worse. Darwinism (unlike ID) doesn’t even exclude anything. It allows for convergent evolution (statistically impossible), stagnant evolution (you mean to tell me that for 500 million years there could be no improvement to the horseshoe crab?), punctuated evolution (everything stays the same for a real long time and then evolution kicks into high gear and it all happens so fast there’s no record of it having happened at all), neutral evolution (the blueprints for marvelously useful structures get created in unexpressed DNA by random shuffling, until one day voila, the gene is turned on and the structure appears fully formed). In evolution anything goes and contradictions live in happy harmony with one another. This is science? It’s not even a sound religion.
- Laszlo Bencze

Seeing as how Professor Behe, who wrote this article, believes that “irreducible complexity” disproves The Theory of Evolution and Professor Thornton of the Univ. of Chicago accepts evolutionary theory and, in fact, is working in a related field, it seems reasonable to quote Dr. Thornton’s Research Description:

FUNCTIONAL EVOLUTIONARY GENETICS
We study the mechanisms and dynamics by which genes and the proteins they code for evolved their diverse functions. We employ a synthesis of evolutionary and phylogenetic techniques with functional molecular biology and biochemistry. Our current model system is a gene family of great biological and biomedical importance.

The Functional Synthesis in molecular biology and evolution
We are interested in two kinds of fundamental issues: 1) first, the nature of evolutionary processes, such as how complexity evolves, whether adaptation proceeds by many small steps or a few large ones, whether interactions among mutations limits the pathways and outcomes that evolution can explore, and whether the outcomes of evolution are deterministic or contingent upon low-probability chance events; and 2) the genetic, biochemical, and biophysical mechanisms by which proteins evolve new functions. All of these questions depend upon the map that relates changes in gene sequence to changes in gene function and, ultimately, in phenotype. These issues remain unresolved because evolutionary biologists have, until recently, ignored the connection between genotype and phenotype by treating genes as mere strings of letters. We have helped to develop and articulate the Functional Synthesis in molecular biology and evolution — a combination of evolutionary approaches for reconstructing history with the experimental strategies of molecular biology and biochemistry to rigorously test hypotheses about the mechanisms of evolution. This approach is uniquely powerful for elucidating both the proximal and ultimate causes of protein function.

Ancestral gene resurrection
We have played an important role in developing a new strategy for studying protein evolution called ancestral gene resurrection. We use computational phylogenetic methods to infer ancestral sequences, followed by gene synthesis to synthesize them and experimental techniques to characterize them. We use cell biological, biochemical, and biophysical methods, as well as (by collaboration) X-ray crystallography and molecular dynamics approaches, to elucidate the functions, structures, and biophysical properties of ancestral proteins. With ancient proteins in hand, we can also introduce the mutations that occurred during crucial evolutionary periods to test hypotheses about the the specific effects caused by each historical genetic change.

Molecular evolution of hormones and their receptors
How did hormones and their diverse functions in humans and other animals evolve? We study the evolution of vertebrate steroid hormones — such as estrogen, testosterone, and the stress hormone cortisol — and the receptor proteins that mediate these hormones’ effects on the body’s cells. Our goal is to reveal the specific molecular events by which hormones, receptors, and their DNA targets evolved their specific partnerships during the last 600 million years or so. We are characterizing receptor biodiversity across the animal kingdom, testing hypotheses about the functions of ancient proteins, and determining the specific mutations and changes in protein structure by which new receptor functions evolved hundreds of millions of years ago.

Phylogenetic techniques
We are also evaluating and developing new phylogenetic methods for analyzing gene family evolution. We are particularly interested in understanding how uncertainty and heterogeneity in the evolutionary process affects the accuracy of current techniques for reconstructing phylogenies and inferring ancestral sequences. We also develop new methods that perform better when sequences evolve with a high degree of complexity.

It’s quite clear that Thornton is comfortable with and deals with “a high degree of complexity”.

"For two millennia, the design argument provided an intellectual foundation for much of Western thought. From classical antiquity through the rise of modern science, leading philosophers, theologians, and scientists. From Plato to Aquinas to Newton, maintained that nature manifests the design of a preexistent mind or intelligence. Moreover, for many Western thinkers, the idea that the physical universe reflected the purpose or design of a preexistent mind, a Creator, served to guarantee humanity's own sense of purpose and meaning. Yet today in nearly every academic discipline from law to literary theory, from behavioral science to biology, a thoroughly materialistic understanding of humanity and its place in the universe has come to dominate. Free will, meaning, purpose, and God have become pejorative terms in the academy. Matter has subsumed mind; cosmos replaced Creator."
- Steven Meyer

Excerpt from Pulitzer Prize-winning author Daniel Walker Howe’s What Hath God Wrought: The Transformation of America, 1815-1844, p. 464:

As this chapter is written in the early twenty-first century, the hypothesis that the universe reflect intelligent design has provoked a bitter debate in the United States. How very different was the intellectual world of the early nineteenth century! Then, virtually everyone believed in intelligent design. Faith in the rational design of the universe underlay the world-view of the Enlightenment, shared by Isaac Newton, John Locke, and the American Founding Fathers. Even the outspoke critics of Christianity embraced not atheism but deism, that is, belief in an impersonal, remote deity who had created the universe and designed it so perfectly that it ran along of its own accord, following natural laws without need for further divine intervention. The common used expression “the book of nature” referred to the universal practice of viewing nature as a revelation of God’s power and wisdom. Christians were fond of saying that they accepted two divine revelations: the Bible and the book of nature. For desists like Thomas Paine, the book of nature alone sufficed, rendering what he called the “fables” of the Bible superfluous. The desire to demonstrate the glory of God, whether deist or – more commonly – Christian, constituted one of the principal motivations for scientific activity in the early republic, along with national pride, the hope for useful applications, and, of course, the joy of science itself.

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