The complexity of creating two sequential or simultaneous mutations that would confer improved survival has been studied in the malaria parasite when exposed to chloroquine. The actual incidence of two base-pair mutations leading to two changed amino acids leading to resistance has been shown to be 1 in 1020 cases (42). To better understand this incidence, the likelihood that Homo sapiens would achieve any single mutation of the kind required for malaria to become resistant to chloroquine (a simple shift of two amino acids) would be 100 million times 10 million years (many times the age of the universe). This example has been used to further explain the difficulty in managing more than one mutation to achieve benefit.The reference is to The Edge of Evolution by Michael Behe. His book was published in 2007 but I never got around to reviewing it thoroughly—partly because it's so difficult to explain where he goes wrong.1 Here's my take on one part of the book: The Two Binding Sites Rule. This post covers "chloroquine-complexity clusters" (CCC).
Behe discusses chloroquine resistance in the malaria parasite Plasmodium falciparum. He notes that one of the common mutations requires two amino acid changes in a gene that encodes an ion transporter. This double mutation is rare—he estimates that it arose less than ten times since chloroquine started to be used as a treatment for malaria. Given the size of the Plasmodium population, this corresponds to a frequency of about 10-20. That's the frequency of two mutations occurring simultaneously since the error frequency of DNA replication is about 10-10 (10-10 × 10-10 = 10-20). This is what you would expect if each of the single mutations is deleterious and the only way the double mutation could arise is when the two mutations occur simultaneously in the same individual.2
Put more pointedly, a double CCC is a reasonable first place to draw a tentative line marking the edge of evolution for all life on earth. We would not expect such an event to happen in all of the organisms that have ever lived over the entire history of life on this planet. So if we do find features of life that would have required a double CCC or more, then we can infer that they likely did not arise by a Darwinian process. [p. 63]Behe is correct, provided that all his assumption are valid.
For some species, the edge of evolution is a single CCC. Humans are an example. Assuming that over the course of human evolution the average population size is one million individuals—a generous assumption—and assuming an average generation time of 10 years—a reasonable assumption—then a CCC will only arise in 1020/106 = 1014 generations. This corresponds to 1015 years.
On average, for humans to achieve a mutation like this by chance, we would need to wait a hundred million times ten million years. Since that is many times the age of the universe, it's reasonable to conclude the following: No mutation that is of the same complexity as chloroquine resistance in malaria arose by Darwinian evolution in the line leading to humans in the past ten million years. [p. 61, Behe's emphasis]This is where Joseph A. Kuhn gets his information in the paragraph quoted at the top of this posting. I assume that IDiots like Dr. Kuhn will accept without question the word of a scientist like Michael Behe but not the word of thousands of other expert scientists who study evolution. Isn't that strange?
Now let's return to the assumption that Behe makes. He assumes that there are cases where two mutations must occur simultaneously in order to achieve some complex adaptation. He argues that each individual mutation is disadvantageous so it will be eliminated from the population by negative selection before a second mutation can occur in the same gene. There are two problems with this assumption.
First, the actual example he uses, chloroquine resistance in the malaria parasite Plasmodium falciparum is wrong. The are strains of Plasmodium that carry one of the mutations and not the other (Cooper et al. 2007). It looks like the single mutation is not deleterious but neutral. This is thought to be a common mechanism of acquiring complex adaptations that require two or more mutations in the same gene. There are plenty of examples of such intragene epistasis.
I hope most readers understand that neutral mutations can persist in populations for long periods of time. They can even become fixed.
But let's not quibble about the actual example that Behe uses. The principle is sound; namely, that there almost certainly are examples where a double mutation will be beneficial but each individual mutation is detrimental. The probability that the two mutations will arise simultaneously in the same individual is 10-20 as Behe says. If that's what has to happen then this really is beyond the edge of evolution ... or is it?
No, it's not. It's not true that deleterious mutations are quickly eliminated from a population. According the modern Nearly Neutral Theory, slightly deleterious mutations can persist for hundreds of generations and can even become fixed in the population. It depends on the strength of negative selection (i.e. the selection coefficient) and the size of the population. In small populations, slightly deleterious alleles are invisible to selection and their frequency is entirely controlled random genetic drift.
Thus, even if we accept Behe's assumption that each of the mutations is deleterious, it does NOT follow that they will be quickly eliminated by natural selection. It's quite possible to have a population carrying a slightly deleterious mutation then have a second mutation occur that makes the allele beneficial. In this case the probability is much less than 10-20 and such an allele (double mutation) is well inside the edge of evolution.
Mutations like this are known to occur in the evolving E. coli strains of Richard Lenski [Evolution in Action and Michael Behe's Reaction] (Woods et al. 2011). For more information on the presence of deleterious alleles in a population and what it means for Behe's argument see Mutations and Complex Adaptations where I quote Michael Lynch, the leading expert on this sort of thing.
It's important to understand that there's a difference between the probability that a mutation will occur and the probability that the new allele will become fixed in the population. They are not the same thing.
It's important to understand that beneficial alleles won't always be fixed; in fact, the vast majority will be lost before they ever reach significant frequency in a population.
It's important to understand that neutral alleles can persist for a very long time and may even become fixed in the population. That's why populations contain so much variability. Additional mutations may convert a neutral allele to a highly beneficial allele and this is likely a route to many complex adaptations.
It's important to understand that random genetic drift can cause slightly deleterious alleles to persist in a population. Subsequent mutations can convert a deleterious allele to a beneficial one. This is how you get beneficial double-mutant alleles even though both single mutations might be harmful. The persistence of neutral and/or deleterious alleles in a population is not Darwinian evolution so if that's the only kind of evolution you know about then you will never understand evolution.
1. Michael Behe is the best Intelligent Design Creationist. Most of his arguments are based on a reasonable knowledge of biochemistry and evolution. He accepts common descent. Many critics of Behe fail to appreciate his arguments. There are quite a few bad reviews of The Edge of Evolution (e.g. Another Bad Review of The Edge of Evolution, Chalk Up One for the Intelligent Design Creationists ).
2. Behe ignores the probability of fixation. He assumes that as soon as a beneficial mutation occurs it will be fixed in the population. That's not correct, of course, because the probability of fixation depends on the selection coefficient (s). It's approximately 2s. For a very beneficial mutation, as in chloroquine resistance, the selection coefficient might be 0.1 and the probability of fixation would be 20%. That still means that the mutation will be lost 80% of the time! This omission doesn't hurt Behe's argument because including the probability of fixation only makes his case stronger!
Cooper, R.A., Lane, K.D., Deng, B., Mu, J., Patel, J.J., Wellems, T.E., Su, X., and Ferdig, M.T. (2007) Mutations in transmembrane domains 1, 4 and 9 of the Plasmodium falciparum chloroquine resistance transporter alter susceptibility to chloroquine, quinine and quinidine. Mol Microbiol. 63:270-8. [PubMed] [doi: 10.1111/j.1365-2958.2006.05511.x]
Woods RJ, Barrick JE, Cooper TF, Shrestha U, Kauth MR, Lenski RE. (2011) Second-order selection for evolvability in a large Escherichia coli population. Science 331:1433-6. [PubMed] [doi: 10.1126/science.1198914]