The Evolutionary Origins of Irreducible Complexity, Part 5

| By Dennis Venema on Letters to the Duchess

Note: One of the challenges for discussing evolution within evangelical Christian circles is that there is widespread confusion about how evolution actually works. In this (intermittent) series, I discuss aspects of evolution that are commonly misunderstood in the Christian community. In this post, we continue to examine evidence that proteins in irreducibly complex (IC) systems can form and refine new interactions through gradual mechanisms.

n the last post in this series, we introduced an elegant experiment on virus evolution done by the Lenski group, and suggested that, despite Behe’s claim to the contrary, this work poses some significant challenges to Behe’s arguments. We now turn to those arguments in detail.

Has Behe found the Edge of evolution?

Behe lays out his detailed case for what evolution can and cannot do in his 2007 book The Edge of Evolution. In a chapter called “The two binding-sites rule”, Behe lays out his argument for defining the “edge”– the limit of what random mutation and selection can do to create new protein-protein binding sites:

So one way to get a new binding site would be to change just five or six amino acids in a coherent patch in the right way. This very rough estimation fits nicely with studies that have been done on protein structure. Five or six amino acids might not sound like very much at first, since proteins are often made of hundreds of amino acids. But five or six amino acid substitutions means that reaching the goal requires five or six coherent mutational steps – just to get two proteins to bind to each other. As we saw in the last chapter, even one missing step makes the job much tougher for Darwin than when steps are continuous. If multiple steps are missing, the job becomes exponentially more difficult. (p. 134)

Then after an aside where Behe considers the possibility that some of the mutations might be neutral (and thus not be required to happen simultaneously), he settles on an estimate of three or four simultaneous mutations to effect a new protein-protein binding site:

So let’s suppose that of the five or six changes that have to happen to a protein to make a new binding site, a third of them are neutral. They could occur before the other key mutations, as a separate step, without harm. Although finding the right neutral changes would itself be an improbable step, we’ll again err on the conservative side and discount the average number of neutral mutations from the average number of total necessary changes. That leaves three or four amino acid changes that might cause trouble if they occur singly. For the Darwinian step in question, they must occur together. Three or four simultaneous mutations is like skipping two or three steps on an evolutionary staircase. (p. 134)

Note well: Behe’s model is based on an assumption that new protein-protein binding sites require multiple, simultaneous amino acid substitutions. Behe continues the argument:

Although two or three missing steps doesn’t sound like much, that’s one or two more Darwinian jumps than were required to get chloroquine resistance in malaria. In chapter 3 I dubbed that level a “CCC”, a “chloroquine complexity cluster,” and showed that its odds were 1 in 1020 births… Now suppose that, in order to acquire some new, useful property, not just one but two new protein-binding sites had to develop. A CCC requires, on average, 1020, a hundred billion billion, organisms – more than the number of mammals that has ever existed on earth. So if other things were equal, the likelihood of getting two new binding sites would be what we called in Chapter 3 a “double CCC”- the square of a CCC, or one in ten to the fortieth power. Since that’s more cells than likely have ever existed on earth, such an event would not be expected to have happened by Darwinian processes in the history of the world. (pp. 134-135)

Again, note well: in his estimation of the probability of generating two new protein-protein binding sites that perform a specific function, Behe calculates it as the square of the probability of getting one. This means that Behe is assuming that the two probabilities are independent, and thus all the non-neutral mutations (for both new binding sites) occur simultaneously. From this calculation, he concludes:

Admittedly, statistics are all about averages, so some freak event like this might happen – it’s not ruled out by force of logic. But it is not biologically reasonable to expect it, or less likely events that occurred in the common descent of life on earth. In short, complexes of just three or more different proteins are beyond the edge of evolution… And the great majority of proteins in the cell work in complexes of six or more. Far beyond that edge. (p. 135)

Indeed, mutations that simultaneously changed six to eight amino acids to instantaneously bring about two new protein-protein binding sites would be a freak event. (Note: I am aware that the precise numbers Behe uses have been criticized, but I’ll assume them for the sake of argument). The real question, though, is whether new protein-protein binding sites require simultaneous mutations. If they do, then Behe might have a case. But if new binding sites can arise one amino acid substitution at a time, however, then Behe’s case is based on a flawed assumption. In this case, protein complexes could add new binding partners one protein at a time, and build up systems of numerous proteins gradually, in a step-wise manner. Moreover, if one new binding site can arise gradually, then it is reasonable to expect that multiple binding sites could also arise without requiring simultaneous mutations.

Adding new protein binding partners, one amino acid substitution at a time

This is where the experiment done by the Lenski group on λ phage evolution (that we introduced in the last post in this series) becomes a key test of Behe’s hypothesis that simultaneous mutations are required for new protein-protein binding sites. (Readers may wish to refresh their memory of this experiment before continuing). The key points are as follows:

  1. For protein J of λ phage to bind to the new partner, OmpF, at least four amino acid substitutions were required before the new binding ability arose. Only with the fourth substitution did the new binding take place.
  2. The probability of these four mutation events happening simultaneously is pretty much zero (approximately one in a thousand trillion trillion). This is well beyond the probability “edge” that Behe claims.
  3. In repeated experiments, the λ phage managed to “find” these mutations over and over again without much trouble.
  4. Subsequent analysis showed that the amino acid substitutions happened sequentiallynot simultaneously.

Over the edge, with ease

As we have seen, Behe’s argument for defining the edge of what evolution can do is based on his assumption that multiple mutations producing certain amino acid substitutions must occur at the same time in order for new protein-protein binding sites to arise. What the Lenski experiments on λ phage demonstrate, however, is that new protein–protein binding sites can arise just fine by accumulating random amino acid substitutions one at a time, even if numerous mutations are needed to achieve the new binding properties. Moreover, they can arise just fine by many different routes, and not always with the exact same mutations present, and this result can be repeated in the lab over and over.

In short, the fundamental assumption of Behe’s model has not stood up to experimental scrutiny. If new protein-protein binding sites can (and do) arise in this way, Behe’s assertion that several mutations must occur at the same time falls apart, and with it his proposed “edge” of what evolution can do. Behe has drawn a line in the sand, but we’ve watched evolution stroll right over it as if it wasn’t there—one amino acid substitution at a time.

In the next post in this series, we’ll return to looking at the p24-2 and Éclair genes of Drosophila melanogaster, and consider Behe’s response to the evidence that these proteins have developed new functions and interactions within the last three million years.

For further reading:

Behe, M.J. Darwin’s Black Box: the Biochemical Challenge to Evolution. Free Press, New York, 1996.
Behe, M.J. The Edge of Evolution: the Search for the Limits of Darwinism. Free Press, New York, 2007.
Meyer, J.R., Dobias, D.T., Weitz, J.S., Barrick, J.E., Quick, R.T., and Lenski, R.E. (2012). Repeatability and contingency in the evolution of a key innovation in phage lambda. Science 335; 428-432.


About the Author

Dennis Venema

Dennis Venema is professor of biology at Trinity Western University in Langley, British Columbia and Fellow of Biology for BioLogos. He holds a B.Sc. (with Honors) from the University of British Columbia (1996), and received his Ph.D. from the University of British Columbia in 2003. His research is focused on the genetics of pattern formation and signaling using the common fruit fly Drosophila melanogaster as a model organism. Dennis is a gifted thinker and writer on matters of science and faith, but also an award-winning biology teacher—he won the 2008 College Biology Teaching Award from the National Association of Biology Teachers. He and his family enjoy numerous outdoor activities that the Canadian Pacific coast region has to offer.