Neuron and antibodies, immunoglobulin, Y-shaped protein produced mainly by plasma cells
Image licensed via Adobe Stock
Michael J. Behe A (R)evolutionary Biologist

Nature publishes paper on the edge of evolution, Part 1


Nature has published an interesting paper recently which places severe limits on Darwinian evolution. This is the first of several posts discussing it.

The manuscript, from the laboratory of Joseph Thornton at the University of Oregon, is entitled “An epistatic ratchet constrains the direction of glucocorticoid receptor evolution”. ( ) The work is interpreted by its authors within a standard Darwinian framework. Nonetheless, like the important work over the years of Michigan State’s Richard Lenski on laboratory evolution of E. coli, which has shown trillions of bacteria evolving under selection for tens of thousands of generations yielding just broken genes and minor changes, the new work demonstrates the looming brick wall which confronts unguided evolution in at least one system. And it points strongly to the conclusion that such walls are common throughout all of biology.

In the paper Bridgham et al (2009) continue their earlier work on steroid hormone receptor evolution. Previously they had constructed in the laboratory a protein which they inferred to be the ancestral sequence of two modern hormone receptors abbreviated GR and MR (Bridgham et al 2006). They then showed that if they changed two amino acid residues in the inferred ancestral receptor protein into ones which occur in GR, they could change its binding specificity somewhat in the direction of modern GR’s specificity. (All the work was done on molecules in the laboratory. No measurements were made of the selective value of the changes in real organisms in nature. Thus any relevance to actual biology is speculative.) They surmised that a gene duplication plus sequence diversification could have given rise to MR and GR. As I wrote in a comment at the time ( ), that was interesting work, and the conclusion was reasonable, but the result was exceedingly modest and well within the boundaries that an intelligent design proponent like myself would ascribe to Darwinian processes. After all, the starting point was a protein which binds several steroid hormones, and the ending point was a slightly different protein that binds the same steroid hormones with slightly different strengths. How hard could that be?

Well, it turns out that Darwinian evolution can have a lot of trouble accomplishing even that simple task, or at least its opposite. In the new paper the authors try the reverse experiment. They begin with the more modern hormone receptor (which is more restrictive in the steroids it binds) and ask whether a Darwinian process could get the ancestral activity back (which is more permissive). Their answer is no, it couldn’t. They show that a handful of amino acid residues in the more recent receptor would first have to be changed before it could act as the ancestral form is supposed to have done, and that is very unlikely to occur. In other words, the new starting point is also a protein which binds a steroid hormone, and the new desired ending point is also a slightly different protein that binds steroid hormones. How hard could that be? But it turns out that Darwinian processes can’t reach it, because several amino acids would have to be altered before the target activity kicked in.

A number of points can be drawn from this fine work:

  • The central point of The Edge of Evolution was tat if several amino acids of a protein must be changed before a certain selective effect is available, then that is effectively beyond the reach of Darwinian processes. Bridgham et al (2009) confirm that conclusion. (As an aside, it would make a good project for a sociologist of science to ask why the same conclusion is met with howls of protest when presented by a Darwinian skeptic such as myself, but garners praise when presented by someone else.)
  • There is no reason to think the protein studied by Bridgham et al (2009) is unusual in its difficulty of developing a binding site for even a relatively closely-related substance. In fact, in the absence of strong opposing data, that should be the default, reasonable assumption.
  • That same reasonable assumption counts strongly against any two unrelated proteins easily developing a binding site for each other.
  • That reasonable assumption therefore negates all woolly Darwinian evolutionary scenarios where critical protein binding sites are assumed without justification to pop up when needed (such as, say, in the building of multiprotein structures like the cilium or flagellum).
  • Thus the work strongly supports the conclusion of Edge that Darwinian processes are highly unlikely to have built the complex molecular machinery of the cell.


Bridgham,J.T., Ortlund,E.A., and Thornton,J.W. 2009. An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461:515-519.

Bridgham,J.T., Carroll,S.M., and Thornton,J.W. 2006. Evolution of hormone-receptor complexity by molecular exploitation. Science 312:97-101.

Michael J. Behe

Senior Fellow, Center for Science and Culture
Michael J. Behe is Professor of Biological Sciences at Lehigh University in Pennsylvania and a Senior Fellow at Discovery Institute’s Center for Science and Culture. He received his Ph.D. in Biochemistry from the University of Pennsylvania in 1978. Behe's current research involves delineation of design and natural selection in protein structures. In his career he has authored over 40 technical papers and three books, Darwin Devolves: The New Science About DNA that Challenges Evolution, Darwin’s Black Box: The Biochemical Challenge to Evolution, and The Edge of Evolution: The Search for the Limits of Darwinism, which argue that living system at the molecular level are best explained as being the result of deliberate intelligent design.