The Edge of Evolution

by Michael J Behe

  10.Nourse, A. E. 1963. Tiger by the Tail. In Fifty Short Science Fiction Tales, eds. I. Asimov and G. Conklin. New York: Collier Books. pp. 185–91.

  11.Rathod, P. K., McErlean, T., and Lee, P. C. 1997. Variations in frequencies of drug resistance in Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 94:9389–93; Le Bras J., and Durand, R. 2003. The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum. Fundam. Clin. Pharmacol. 17:147–53.

  12.Gassis, S., and Rathod, P. K. 1996. Frequency of drug resistance in Plasmodium falciparum: a nonsynergistic combination of 5-fluoroorotate and atovaquone suppresses in vitro resistance. Antimicrob. Agents Chemother. 40:914–19.

  13.White, N. J. 1999. Delaying antimalarial drug resistance with combination chemotherapy. Parassitologia 41:301–8.

  14.Gassis and Rathod. 1996.

  15.White. 1999.

  16.White, N. J. 2004. Antimalarial drug resistance. J. Clin. Invest. 113:1084–92.

  17.White. 1999.

  18.Takahata, N. 1993. Allelic genealogy and human evolution. Mol. Biol. Evol. 10:2–22. Here I am considering the “census” population size—the actual number of humans. The “effective” human population size—which is calculated from the genetic diversity of the population—is much smaller, perhaps only ten thousand or so.

  19.Ten million years divided by one generation per ten years times a million creatures per generation.

  20.The effective population size of the prolific house mouse has been estimated at between 450,000 and 810,000 (Keightley, P. D., Lercher, M. J., and Eyre-Walker, A. 2005. Evidence for widespread degradation of gene control regions in hominid genomes. PLoS. Biol. 3:e42). For the ancestor of humans and chimps the estimate is 20,000 (Rannala, B., and Yang, Z. 2003. Bayes estimation of species divergence times and ancestral population sizes using DNA sequences from multiple loci. Genetics 164:1645–56).

  21.Mammals are thought to have arisen about 250 million years ago.

  22.Le Bras, J., Durand, R. 2003. The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum. Fundam. Clin. Pharmacol. 17:147–53.

  23.Whitman, W. B., Coleman, D. C., Wiebe, W. J. 1998. Prokaryotes: the unseen majority. Proc. Natl. Acad. Sci. USA 95:6578–83.

  4 What Darwinism Can Do

  1.Mayr, E. 1991. One long argument: Charles Darwin and the genesis of modern evolutionary thought. Cambridge, Mass.: Harvard University Press, p. 36.

  2.Darwin, C. 1859. The origin of species. New York: Bantam Books.

  3.The genetic code is redundant, with some amino acids being coded for by multiple three-nucleotide sequences of DNA. So if a mutation merely switches one such redundant sequence for another, no change in amino acid sequence results.

  4.National Library of Medicine. Genes and Disease. National Institutes of Health. 2004. The normal role of huntingtin is currently unknown.

  5.Greenwood, B. 2002. The molecular epidemiology of malaria. Trop. Med. Int. Health 7:1012–21.

  6.Lim, A. S., Cowman, A. F. 1996. Plasmodium falciparum: chloroquine selection of a cloned line and DNA rearrangements. Exp. Parasitol. 83:283–94.

  7.Drake, J. W., Charlesworth, B., Charlesworth, D., and Crow, J. F. 1998. Rates of spontaneous mutation. Genetics 148:1667–86.

  8.Lynch, M., Conery, J. S. 2000. The evolutionary fate and consequences of duplicate genes. Science 290:1151–55. However, other workers have estimated a much lower rate of gene duplication (Gao, L. Z., Innan, H. 2004. Very low gene duplication rate in the yeast genome. Science 306:1367–70).

  9.Dayhoff, M. O., and National Biomedical Research Foundation. 1973. Atlas of protein sequence and structure, vol. 5: supplement. Silver Spring, Md.: National Biomedical Research Foundation.

  10.Chang, L. Y., and Slightom, J. L. 1984. Isolation and nucleotide sequence analysis of the beta-type globin pseudogene from human, gorilla and chimpanzee. J. Mol. Biol. 180:767–84.

  11.Bapteste, E., Susko, E., Leigh, J., MacLeod, D., Charlebois, R. L., and Doolittle, W. F. 2005. Do orthologous gene phylogenies really support tree-thinking? BMC Evol. Biol. 5:33.

  12.Dujon, B., et al. 2004. Genome evolution in yeasts. Nature

  13.Kellis, M., Birren, B. W., Lander, E. S. 2004. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature 428:617–24.

  14.Dujon et al. 2004.

  15.Other genome duplications also seem to have had little discernible effect. For example, about half of all angiosperm (flowering plant) species are polyploid, and the number varies according to family and genus (Coyne, J. A., and Orr, H. A. 2004. Speciation. Sunderland, Mass.: Sinauer Associates, Chapter 9). Thus polyploidy apparently has no overwhelming advantage or disadvantage. The vertebrate lineage is thought to have undergone several rounds of genome duplication, which was speculated to have contributed to organismal complexity (Sidow, A. 1996. Gen(om)e duplications in the evolution of early vertebrates. Curr. Opin. Genet. Dev. 6:715–22). However, other workers see no connection (Donoghue, P. C. J., and Purnell, M. A. 2005. Genome duplication, extinction and vertebrate evolution. Trends in Ecology and Evolution 20:312–19).

  16.Hayton, K. and Su, X. Z. 2004. Genetic and biochemical aspects of drug resistance in malaria parasites. Curr. Drug Targets Infect. Disord. 4:1–10.

  17.Ibid.

  18.Vaughan, A., Rocheleau, T., and ffrench-Constant, R. 1997. Site-directed mutagenesis of an acetylcholinesterase gene from the yellow fever mosquito Aedes aegypti confers insecticide insensitivity. Exp. Parasitol. 87:237–44.

  19.“Non-silent point mutations within structural genes are the most common cause of target-site resistance. For selection of the mutations to occur, the resultant amino acid change must reduce the binding of the insecticide without causing a loss of primary function of the target site. Therefore the number of possible amino acid substitutions is very limited. Hence, identical resistance-associated mutations are commonly found across highly diverged taxa” (Hemingway, J., and Ranson, H. 2000. Insecticide resistance in insect vectors of human disease. Annu. Rev. Entomol. 45:371–91).

  20.Pelz, H. J., Rost, S., Hunerberg, M., Fregin, A., Heiberg, A. C., Baert, K., Macnicoll, A. D., Prescott, C. V., Walker, A. S., Oldenburg, J., and Muller, C. R.2005. The genetic basis of resistance to anticoagulants in rodents. Genetics 170:1839–47.

  21.A similar mutation has also been observed in a human patient treated with the chemical as an anticoagulant.

  22.Chen, I., DeVries, A. L., Cheng, C. H. 1997. Evolution of antifreeze glycoprotein gene from a trypsinogen gene in Antarctic notothenioid fish. Proc. Natl. Acad. Sci. USA 94:3811–16.

  23.The sequence is not a perfect repeat. Apparently, some point mutations have also accumulated.

  24.Chen et al. 1997.

  25.Cheng, C. H., and Chen L. 1999. Evolution of an antifreeze glycoprotein. Nature 401:443–44.

  26.Davies, P. L., Baardsnes, J., Kuiper, M. I., Walker, V. K. 2002. Structure and function of antifreeze proteins. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 357:927–35.

  27.Zachariassen, K. E., and Kristiansen, E. 2000. Ice nucleation and anti-nucleation in nature. Cryobiology 41:257–79.

  28.Coluzzi, M. 1999. The clay feet of the malaria giant and its African roots: hypotheses and inferences about origin, spread and control of Plasmodium falciparum. Parassitologia 41:277–83; Sachs, J., and Malaney, P. 2002. The economic and social burden of malaria. Nature 415:680–85.

  5 What Darwinism Can’t Do

  1.Kozminski, K. G., Johnson, K. A., Forscher, P., and Rosenbaum, J. L.1993. A motility in the eukaryotic flagellum unrelated to flagellar beating. Proc. Natl. Acad. Sci. USA 90:5519–23; Sloboda, R. D. 2002. A healthy understanding of intraflagellar transport. Cell Motil. Cytoskeleton 52:1–8.

  2.www.yale.edu/rosenbaum/rose

  3.Cole, D. G. 2003. The intraflagellar transport machinery of Chlamydomonas reinhardtii. Traffic 4:435–42.

  4.Song, L., and Dentler, W. L. 2001. Flagellar protein dynamics in Chlamydomonas. J. Biol. Chem. 2
76:29754–63.

  5.Cole, D. G. 2003. The intraflagellar transport machinery of Chlamydomonas reinhardtii. Traffic 4:435–42. When the amount of a protein that’s normally part of complex A was experimentally decreased, the rest of the proteins found in complex A went down, too, but not those in complex B. So A and B might be separately regulated in the cell.

  6.Apparently, IFT is needed to ensure that nodal cilia are made. Nodal cilia are somewhat altered compared to most cilia. (They have a 9+0 structure rather than the common 9+2 structure, lacking the two central single microtubules of most cilia.) In the mutant mice nodal cilia were completely missing. Nodal cilia, which have a curious circular motion rather than the typical ciliary back-and-forth motion, are hypothesized to drive a flow of liquid that carries developmental factors to their proper positions (Scholey, J. M. 2003. Intraflagellar transport. Annu. Rev. Cell Dev. Biol. 19:423–43).

  7.Pazour, G. J., Baker, S. A., Deane, J. A., Cole, D. G., Dickert, B. L., Rosenbaum, J. L., Witman, G. B., and Besharse, J. C. 2002. The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J. Cell Biol. 157:103–13.

  8.Marszalek, J. R., Liu, X., Roberts, E. A., Chui, D., Marth, J. D., Williams, D. S., and Goldstein, L. S. 2000. Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. Cell 102:175–87.

  9.Sloboda, R. D. 2002. A healthy understanding of intraflagellar transport. Cell Motil. Cytoskeleton 52:1–8.

  10.Farley, J. 1977. The spontaneous generation controversy from Descartes to Oparin. Baltimore: Johns Hopkins University Press, p. 73.

  11.The best example, in my opinion, is by University of Delaware biology professor John McDonald (http://udel.edu/~mcdonald/oldmousetrap.html).

  12.Berriman and coworkers write of trypanosomes: “The proteins of the flagellar axoneme appeared to be extremely well conserved. With the exception of tektin, there are homologs in the three genomes for all previously identified structural components as well as a full complement of flagellar motors and both complex A and complex B of the intraflagellar transport system…. Thus, the 9+2 axoneme, which arose very early in eukaryotic evolution, appears to be constructed around a core set of proteins that are conserved in organisms possessing flagella and cilia” (Berriman, M., et al. 2005. The genome of the African trypanosome Trypanosoma brucei. Science 309:416–22).

  13.But there is never a shortage of Darwinian conjecture. For an example, see Jekely, G., and Arendt, D. 2006. Evolution of intraflagellar transport from coated vesicles and autogenous origin of the eukaryotic cilium. Bioessays 28:191–98. Published in the “Hypotheses” section of the journal, the paper contains statements such as, “What was the initial advantage of membrane polarisation? One possibility is that the specialised membrane patch was advantageous for directional sensing,” and, “It is also possible that compartmentalisation was favoured because of the nature of the receptor-mediated signalling pathways.” In other words, the paper offers speculation.

  14.I discuss the state of the science literature ten years after its original publication in the Afterword of the tenth-anniversary edition of Darwin’s Black Box.

  15.Another example is a paper that takes a “Darwinian perspective” on explaining the evolution of the Type III secretory system. It quotes Charles Darwin in the Origin of Species remarking, “On the view of descent with modification, we may conclude that the existence of organs in a rudimentary, imperfect, and useless condition,…might even have been anticipated in accordance with the views here explained.” This may support Darwin’s idea of common descent, but does not speak to random mutation/natural selection (Pallen, M. J., Beatson, S. A., and Bailey, C. M. 2005. Bioinformatics, genomics and evolution of nonflagellar type-III secretion systems: a Darwinian perspective. FEMS Microbil. Rev. 29:201–29).

  16.Kalir, S., McClure, J., Pabbaraju, K., Southward, C., Ronen, M., Leibler, S., Surette, M. G., and Alon, U. 2001. Ordering genes in a flagella pathway by analysis of expression kinetics from living bacteria. Science 292:2080–83.

  17.Zaslaver, A., Mayo, A. E., Rosenberg, R., Bashkin, P., Sberro, H., Tsalyuk, M., Surette, M. G., and Alon, U. 2004. Just-in-time transcription program in metabolic pathways. Nat. Genet. 36:486–91.

  18.Pearson, H. 2006. Genetics: what is a gene? Nature 441:398–401.

  6 Benchmarks

  1.Coyne, J. A., and Orr, H. A. 2004. Speciation. Sunderland, Mass.: Sinauer Associates, p. 136.

  2.Like the great majority of evolutionary biologists, Orr and Coyne assume an evolutionary framework involving only unintelligent processes, and are dismissive of intelligent design. See Coyne, J. A. The case against intelligent design. The New Republic. August 22, 2005; Orr, H. A. Devolution. The New Yorker. May 30, 2005.

  3.Adam, D. Give six monkeys a computer, and what do you get? Certainly not the Bard. The Guardian. 5-9-2003.

  4.Smith, J. M. 1970. Natural selection and the concept of a protein space. Nature 225:563–64.

  5.Orr, H. A. 2003. A minimum on the mean number of steps taken in adaptive walks. J. Theor. Biol. 220:241–47.

  6.Drake, J. W., Charlesworth, B., Charlesworth, D., and Crow, J. F. 1998. Rates of spontaneous mutation. Genetics 148:1667–86.

  7.Kimura, M. 1983. The neutral theory of molecular evolution. Cambridge: Cambridge University Press.

  8.For example, see Gavrilets, S. 2004. Fitness landscapes and the origin of species. Princeton, N.J.: Princeton University Press.

  9.One idea, proposed by Sewall Wright, to get around a rugged landscape is called the “shifting balance theory” (Wright, S. 1982. The shifting balance theory and macroevolution. Annu. Rev. Genet. 16:1–19), where a large population is subdivided into smaller, local ones, which can become less fit, and then perhaps begin to ascend another nearby, higher fitness peak. Wright’s idea remains controversial.

  10.Orr, H. A. 2003. A minimum on the mean number of steps taken in adaptive walks. J. Theor. Biol. 220:241–47.

  11.“While thus employed, the heavy pewter lamp suspended in chains over his head, continually rocked with the motion of the ship, and for ever threw shifting gleams and shadows of lines upon his wrinkled brow, till it almost seemed that while he himself was marking out lines and courses on the wrinkled charts, some invisible pencil was also tracing lines and courses upon the deeply marked chart of his forehead.”

  12.Jacob, F. 1977. Evolution and tinkering. Science 196:1161–66. Jacob argued that an engineer made special parts for each new job, whereas a tinkerer reused old parts. Since parts of organisms appear to be related, Jacob thought that pointed to blind groping rather than foresight. Yet his argument addresses common descent, not random mutation. Whatever the merits of the analogy of tinker versus engineer in reusing parts, it simply doesn’t address the question of whether guidance is needed to make a structure. Jacob didn’t try to explain how complex structures could arise by chance, or by tinkering.

  13.Behe, M. J. 1996. Darwin’s black box: the biochemical challenge to evolution. New York: The Free Press, p. 39.

  7 The Two-Binding-Sites Rule

  1.Alberts, B. 1998. The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell 92:291–94.

  2.Woodson, S. A. 2005. Biophysics: assembly line inspection. Nature 438:566–67.

  3.Nooren, I. M., and Thornton, J. M. 2003. Diversity of protein-protein interactions. EMBO J. 22:3486–92.

  4.Pauling, L. 1940. A theory of the structure and process of formation of antibodies. Journal of the American Chemical Society 62:2643–57. Pauling won the Nobel Prize for Chemistry in 1954 and for Peace in 1962.

  5.Perelson, A. S., and Oster, G. F. 1979. Theoretical studies of clonal selection: minimal antibody repertoire size and reliability of self-non-self discrimination. J. Theor. Biol. 81:645–70; Segel, L. A., and Perelson, A. S. 1989. Shape space: an approach to the evaluation of cross-reactivity effects, stability and controllability in the immune system. Immunol. Lett. 22:91
–99; De Boer, R. J., and Perelson, A. S. 1993. How diverse should the immune system be? Proc. Biol. Sci. 252:171–75; Smith, D. J., Forrest, S., Hightower, R. R., and Perelson, A. S. 1997. Deriving shape space parameters from immunological data. J. Theor. Biol. 189:141–50.

  6.A properly working protein will bind to just one or a few specific partners. However, because the interiors of most folded proteins are oily, if a protein accidentally unfolds (“denatures”), it might stick to almost everything in sight. Nonspecific aggregation is almost always detrimental to a cell (Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C. M., and Stefani, M. 2002. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416:507–11). Cells take great care to avoid it, with systems that dispose of misfolded proteins. So such nonspecific aggregation is not a model for how functional, specific, protein-protein interactions could develop in the cell.

  7.Gavin, A. C., et al. 2002. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415:141–47; Giot, L., et al. 2003. A protein interaction map of Drosophila melanogaster. Science 302:1727–36; Li, S., et al. 2004. A map of the interactome network of the metazoan C. elegans. Science 303:540–43; Butland, G., et al. 2005. Interaction network containing conserved and essential protein complexes in Escherichia coli. Nature 433:531–37; LaCount, D. J., et al. 2005. A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 438:103–7; Gavin, A. C., et al. 2006. Proteome survey reveals modularity of the yeast cell machinery. Nature 440:631–36.