Did design theorist Michael Behe predict this?
Abstract: Mutations in the chloroquine resistance transporter (PfCRT) are the primary determinant of chloroquine (CQ) resistance in the malaria parasite Plasmodium falciparum. A number of distinct PfCRT haplotypes, containing between 4 and 10 mutations, have given rise to CQ resistance in different parts of the world. Here we present a detailed molecular analysis of the number of mutations (and the order of addition) required to confer CQ transport activity upon the PfCRT as well as a kinetic characterization of diverse forms of PfCRT. We measured the ability of more than 100 variants of PfCRT to transport CQ when expressed at the surface of Xenopus laevis oocytes. Multiple mutational pathways led to saturable CQ transport via PfCRT, but these could be separated into two main lineages. Moreover, the attainment of full activity followed a rigid process in which mutations had to be added in a specific order to avoid reductions in CQ transport activity. A minimum of two mutations sufficed for (low) CQ transport activity, and as few as four conferred full activity. The finding that diverse PfCRT variants are all limited in their capacity to transport CQ suggests that resistance could be overcome by reoptimizing the CQ dosage. Paywall
Behe writes that in his Edge of Evolution (2007),
A major point of the book was that if evolution has to skip even one baby step to attain a beneficial state (that is, if even one intermediate in a long and relentlessly detailed evolutionary pathway is detrimental or unhelpful), then the probability of reaching that state decreases exponentially. After discussing a medically important example (see below), I argued that the evolution of many protein interactions would fall into the skip-step category, that multi-protein complexes in the cell were beyond the reach of Darwinian evolution, and that design extended very deeply into life.
However, at the time the book’s chief, concrete example — the need for multiple, specific changes in a particular malarial protein (called PfCRT) for the development of resistance to chloroquine — was an inference, not yet an experimentally confirmed fact. It was really an excellent, obvious inference, because resistance to chloroquine arises much, much less frequently than to other drugs. For example, resistance to the antimalarial drug atovaquone develops spontaneously in every third patient, but to chloroquine only in approximately every billionth one. About PfCRT I wrote, “Since two particular amino acid changes [out of four to eight total changes] occur in almost all of these cases [of chloroquine resistance in the wild], they may both be required for the primary activity by which the protein confers resistance.” The result would be that “the likelihood of a particular [malarial] cell having the several necessary changes would be much, much less than the case [for atovaquone] where it needed to change only one amino acid. That factor seems to be the secret of why chloroquine was an effective drug for decades.” Still, the deduction hadn’t yet been nailed down in the lab.
Now it has, thanks to Summers et al. 2014 …
He says this is the first of three posts. Evolution News & Views doesn’t allow comments, so feel free to offer them here, especially if you intend to read the paper you are trashing.
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