Evolution Icon Evolution

Problem 3: Step-by-Step Random Mutations Cannot Generate the Genetic Information Needed for Irreducible Complexity

Editor’s note: This is Part 3 of a 10-part series based upon Casey Luskin’s chapter, “The Top Ten Scientific Problems with Biological and Chemical Evolution,” in the volume More than Myth, edited by Paul Brown and Robert Stackpole (Chartwell Press, 2014). The full chapter can be found online here. Other individual installments can be found here: Problem 1, Problem 2, Problem 4, Problem 5, Problem 6, Problem 7, Problem 8, Problem 9, Problem 10.

According to evolutionary biologists, once life got started, Darwinian evolution took over and eventually produced the grand diversity we observe today. Under the standard view, a process of random mutation and natural selection built life’s vast complexity one small mutational step at a time. All of life’s complex features, of course, are thought to be encoded in the DNA of living organisms. Building new features thus requires generating new information in the genetic code of DNA. Can the necessary information be generated in the undirected, step-by-step manner required by Darwin’s theory?

Most everyone agrees that Darwinian evolution tends to work well when each small step along an evolutionary pathway provides some survival advantage. Darwin-critic Michael Behe notes that “if only one mutation is needed to confer some ability then Darwinian evolution has little problem finding it.”24 However, when multiple mutations must be present simultaneously to gain a functional advantage, Darwinian evolution gets stuck. As Behe explains, “If more than one [mutation] is needed, the probability of getting all the right ones grows exponentially worse.”25

Behe, a professor of biochemistry at Lehigh University, coined the term “irreducible complexity” to describe systems which require many parts — and thus many mutations — to be present — all at once — before providing any survival advantage to the organism. According to Behe, such systems cannot evolve in the step-by-step fashion required by Darwinian evolution. As a result, he maintains that random mutation and unguided natural selection cannot generate the genetic information required to produce irreducibly complex structures. Too many simultaneous mutations would be required — an event which is highly unlikely to occur.

Observation of this problem is not limited to Darwin-critics. A paper by a prominent evolutionary biologist in the prestigious journal Proceedings of the U.S. National Academy of Science. acknowledges that “simultaneous emergence of all components of a system is implausible.”26 Likewise, University of Chicago evolutionary biologist Jerry Coyne — a staunch defender of Darwinism — admits that “natural selection cannot build any feature in which intermediate steps do not confer a net benefit on the organism.”27 Even Darwin intuitively recognized this problem, as he wrote in Origin of Species:

If it could be demonstrated that any complex organ existed, which could not possibly have been formed by numerous, successive, slight modifications, my theory would absolutely break down.28

Evolutionary scientists like Darwin and Coyne claim they know of no real-world case where Darwinian selection gets blocked in this manner. But they would agree, at least in principle, that there are theoretical limits to what Darwinian evolution can accomplish: If a feature cannot be built by “numerous, successive, slight modifications,” and if “intermediate steps do not confer a net benefit on the organism,” then Darwinian evolution will “absolutely break down.”

The problems are real. Modern biology continues to uncover more and more examples where biological complexity seems to outstrip the information-generative capacity of Darwinian evolution.

Molecular Machines
In his book Darwin’s Black Box, Michael Behe discusses molecular machines which require multiple parts to be present before they could function and confer any advantage on the organism. Behe’s most famous example is the bacterial flagellum — a micromolecular rotary-engine, functioning like an outboard motor on bacteria to propel it through liquid medium to find food. In this regard, flagella have a basic design that is highly similar to some motors made by humans containing many parts that are familiar to engineers, including a rotor, a stator, a u-joint, a propeller, a brake, and a clutch. As one molecular biologist writes in the journal Cell, “[m]ore so than other motors, the flagellum resembles a machine designed by a human.”29 However the energetic efficiency of these machines outperforms anything produced by humans: the same paper found that the efficiency of the bacterial flagellum “could be ~100%.”30

There are various types of flagella, but all use certain basic components. As one paper in Nature Reviews Microbiology acknowledges, “all (bacterial) flagella share a conserved core set of proteins” since “Three modular molecular devices are at the heart of the bacterial flagellum: the rotor-stator that powers flagellar rotation, the chemotaxis apparatus that mediates changes in the direction of motion and the T3SS that mediates export of the axial components of the flagellum.”31 As this might suggest, the flagellum is irreducibly complex. Genetic knockout experiments have shown that it fails to assemble or function properly if any one of its approximately 35 genes are missing.32 In this all-or-nothing game, mutations cannot produce the complexity needed to provide a functional flagellar rotary engine one incremental step at a time, and the odds are too daunting for it to assemble in one great leap. Indeed, the aforementioned Nature Reviews Microbiology paper admitted that “the flagellar research community has scarcely begun to consider how these systems have evolved.”33

Yet the flagellum is just one example of thousands of known molecular machines in biology. One individual research project reported the discovery of over 250 new molecular machines in yeast alone.34 The former president of the U.S. National Academy of Sciences, Bruce Alberts, wrote an article in the journal Cell praising the “speed,” “elegance,” “sophistication,” and “highly organized activity” of these “remarkable” and “marvelous” molecular machines. He explained what inspired those words: “Why do we call the large protein assemblies that underlie cell function protein machines? Precisely because, like machines invented by humans to deal efficiently with the macroscopic world, these protein assemblies contain highly coordinated moving parts.”35 Biochemists like Behe and others believe that with all of their coordinated interacting parts, many of these machines could not have evolved in a step-by-step Darwinian fashion.

But it’s not just multi-part machines which are beyond reach of Darwinian evolution. The protein-parts themselves which build these machines would also require multiple simultaneous mutations in order to arise.

Research Challenges the Darwinian Mechanism
In 2000 and 2004, protein scientist Douglas Axe published experimental research in the Journal of Molecular Biology on mutational sensitivity tests he performed on enzymes in bacteria.36 Enzymes are long chains of amino acids which fold into a specific, stable, three-dimensional shape in order to function. Mutational sensitivity experiments begin by mutating the amino acid sequences of those proteins, and then testing the mutant proteins to determine whether they can still fold into a stable shape, and function properly. Axe’s research found that amino acid sequences which yield stable, functional protein folds may be as rare as 1 in 1074 sequences, suggesting that the vast majority of amino acid sequences will not produce stable proteins, and thus could not function in living organisms.

Because of this extreme rarity of functional protein sequences, it would be very difficult for random mutations to take a protein with one type of fold, and evolve it into another, without going through some non-functional stage. Rather than evolving by “numerous, successive, slight modifications,” many changes would need to occur simultaneously to “find” the rare and unlikely amino acid sequences that yield functional proteins. To put the matter in perspective, Axe’s results suggest that the odds of blind and unguided Darwinian processes producing a functional protein fold are less than the odds of someone closing his eyes and firing an arrow into the Milky Way galaxy, and hitting one pre-selected atom.37

Proteins commonly interact with other molecules through a “hand-in-glove” fit, but these interactions often require multiple amino acids to be ‘just right’ before they occur. In 2004, Behe, along with University of Pittsburgh physicist David Snoke, simulated the Darwinian evolution of such protein-protein interactions. Behe and Snoke’s calculations found that for multicellular organisms, evolving a simple protein-protein interaction which required two or more mutations in order to function would probably require more organisms and generations than would be available over the entire history of the Earth. They concluded that “the mechanism of gene duplication and point mutation alone would be ineffective…because few multicellular species reach the required population sizes.”38

Four years later during an attempt to refute Behe’s arguments, Cornell biologists Rick Durrett and Deena Schmidt ended up begrudgingly confirming he was basically correct. After calculating the likelihood of two simultaneous mutations arising via Darwinian evolution in a population of humans, they found that such an event “would take > 100 million years.” Given that humans diverged from their supposed common ancestor with chimpanzees only 6 million years ago, they granted that such mutational events are “very unlikely to occur on a reasonable timescale.”39

Now a defender of Darwinism might reply that these calculations measured the power of the Darwinian mechanism only within multicellular organisms where it is less efficient because these more complex organisms have smaller population sizes and longer generation times than single-celled prokaryotic organisms like bacteria. Darwinian evolution, the Darwinian notes, might have a better shot when operating in organisms like bacteria, which reproduce more rapidly and have much larger population sizes. Scientists skeptical of Darwinian evolution are aware of this objection, and have found that even within more-quickly evolving organisms like bacteria, Darwinian evolution faces great limits.

In 2010, Douglas Axe published evidence indicating that despite high mutation rates and generous assumptions favoring a Darwinian process, molecular adaptations requiring more than six mutations before yielding any advantage would be extremely unlikely to arise in the history of the Earth.

The following year, Axe published research with developmental biologist Ann Gauger regarding experiments to convert one bacterial enzyme into another closely related enzyme — the kind of conversion that evolutionists claim can easily happen. For this case they found that the conversion would require a minimum of at least seven simultaneous changes,40 exceeding the six-mutation-limit which Axe had previously established as a boundary of what Darwinian evolution is likely to accomplish in bacteria. Because this conversion is thought to be relatively simple, it suggests that more complex biological features would require more than six simultaneous mutations to give some new functional advantage.

In other experiments led by Gauger and biologist Ralph Seelke of the University of Wisconsin, Superior, their research team broke a gene in the bacterium E. coli required for synthesizing the amino acid tryptophan. When the bacteria’s genome was broken in just one place, random mutations were capable of “fixing” the gene. But even when only two mutations were required to restore function, Darwinian evolutionseemed to get stuck, with an inability to regain full function.41

These kind of results consistently suggest that the information required for proteins and enzymes to function is too great to be generated by Darwinian processes on any reasonable evolutionary timescale.

Darwin Skeptics Abound
Drs. Axe, Gauger, and Seelke are by no means the only scientists to observe the rarity of amino acid sequences that yield functional proteins. A leading college-level biology textbook states that “even a slight change in primary structure can affect a protein’s conformation and ability to function.”42 Likewise, evolutionary biologist David S. Goodsell writes:

[O]nly a small fraction of the possible combinations of amino acids will fold spontaneously into a stable structure. If you make a protein with a random sequence of amino acids, chances are that it will only form a gooey tangle when placed in water.43

Goodsell goes on to assert that “cells have perfected the sequences of amino acids over many years of evolutionary selection.” But if functional protein sequences are rare, then it is likely that natural selection will be unable to take proteins from one functional genetic sequence to another without getting stuck in some maladaptive or non-beneficial intermediate stage.

The late biologist Lynn Margulis, a well-respected member of the National Academy of Sciences until her death in 2011, once said “new mutations don’t create new species; they create offspring that are impaired.”44 She further explained in a 2011 interview:

[N]eo-Darwinists say that new species emerge when mutations occur and modify an organism. I was taught over and over again that the accumulation of random mutations led to evolutionary change-led to new species. I believed it until I looked for evidence.45

Similarly, past president of the French Academy of Sciences, Pierre-Paul Grasse, contended that “[m]utations have a very limited ‘constructive capacity'” because “[n]o matter how numerous they may be, mutations do not produce any kind of evolution.”46

Many other scientists feel this way. Over 800 Ph.D. scientists have signed a statement agreeing they “are skeptical of claims for the ability of random mutation and natural selection to account for the complexity of life.”47 Indeed, two biologists wrote in Annual Review of Genomics and Human Genetics: “it remains a mystery how the undirected process of mutation, combined with natural selection, has resulted in the creation of thousands of new proteins with extraordinarily diverse and well optimized functions. This problem is particularly acute for tightly integrated molecular systems that consist of many interacting parts…”48 Perhaps it would be less mysterious if the theoretical conceptions could be expanded beyond unguided evolutionary mechanisms like random mutation and natural selection to explain the origin of complex biological features.

References Cited:
[24.] See Michael Behe, “Is There an ‘Edge’ to Evolution?” at http://www.faithandevolution.org/debates/is-there-an-edge-to-evolution.php
[25.] Ibid.
[26.] Michael Lynch, “Evolutionary layering and the limits to cellular perfection,” Proceedings of the U.S. National Academy of Sciences, www.pnas.org/cgi/doi/10.1073/pnas.1216130109 (2012).
[27.] Jerry Coyne, “The Great Mutator (Review of The Edge of Evolution, by Michael J. Behe),” The New Republic, pp. 38-44, 39 (June 18, 2007).
[28.] Charles Darwin, Origin of Species (1859), Chapter 6, available at http://www.literature.org/authors/darwin-charles/the-origin-of-species/chapter-06.html
[29.] David J. DeRosier, “The turn of the screw: The bacterial flagellar motor,” Cell, 93: 17-20 (1998).
[30.] Ibid.
[31.] Mark Pallen and Nicholas Matzke, “From The Origin of Species to the Origin of Bacterial Flagella,” Nature Reviews Microbiology, 4:788 (2006).
[32.] These experiments have been done on flagella in E. coli and S. typhimurium. See Transcript of Testimony of Scott Minnich, pp. 103-112, Kitzmiller et al. v. Dover Area School Board, No. 4:04-CV-2688 (M.D. Pa., Nov. 3, 2005). Other experimental studies have identified over 30 proteins necessary to form flagella. See Table 1. in Robert M. Macnab, “Flagella,” in Escheria Coli and Salmonella Typhimurium: Cellular and Molecular Biology Vol 1, pp. 73-74, Frederick C. Neidhart, John L. Ingraham, K. Brooks Low, Boris Magasanik, Moselio Schaechter, and H. Edwin Umbarger, eds., (Washington D.C.: American Society for Microbiology, 1987).
[33.] Mark Pallen and Nicholas Matzke, “From The Origin of Species to the Origin of Bacterial Flagella,” Nature Reviews Microbiology, 4:788 (2006).
[34.] See “The Closest Look Ever at the Cell’s Machines,” ScienceDaily.com (January 24, 2006), at http://www.sciencedaily.com/releases/2006/01/060123121832.htm
[35.] Bruce Alberts, “The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists,” Cell, 92:291 (February 6, 1998).
[36.] Douglas D. Axe, “Estimating the Prevalence of Protein Sequences Adopting Functional Enzyme Folds,” Journal of Molecular Biology, 341: 1295-1315 (2004); Douglas D. Axe, “Extreme Functional Sensitivity to Conservative Amino Acid Changes on Enzyme Exteriors,” Journal of Molecular Biology, 301: 585-595 (2000).
[37.] See Stephen C. Meyer, Signature in the Cell: DNA and the Evidence for Intelligent Design, p. 211 (Harper One, 2009).
[38.] Michael Behe and David Snoke, “Simulating Evolution by Gene Duplication of Protein Features That Require Multiple Amino Acid Residues,” Protein Science, 13: 2651-2664 (2004).
[39.] Rick Durrett and Deena Schmidt, “Waiting for Two Mutations: With Applications to Regulatory Sequence Evolution and the Limits of Darwinian Evolution,” Genetics, 180:1501-1509 (2008). For a more detailed discussion of this argument, see Ann Gauger, Douglas Axe, Casey Luskin, Science and Human Origins (Discovery Institute Press, 2012).
[40.] Ann Gauger and Douglas Axe, “The Evolutionary Accessibility of New Enzyme Functions: A Case Study from the Biotin Pathway,” BIO-Complexity, 2011 (1): 1-17.
[41.] Ann Gauger, Stephanie Ebnet, Pamela F. Fahey, and Ralph Seelke, “Reductive Evolution Can Prevent Populations from Taking Simple Adaptive Paths to High Fitness,” BIO-Complexity, 2010 (2): 1-9.
[42.] Neil A. Campbell and Jane B. Reece, Biology, p. 84 (7th ed., 2005).
[43.] David S. Goodsell, The Machinery of Life, pp. 17, 19 (2nd ed., Springer, 2009).
[44.] Lynn Margulis, quoted in Darry Madden, UMass Scientist to Lead Debate on Evolutionary Theory, Brattleboro (Vt.) Reformer (February 3, 2006).
[45.] Lynn Margulis quoted in “Lynn Margulis: Q + A,” Discover Magazine, p. 68 (April, 2011).
[46.] Pierre-Paul Grass�, Evolution of Living Organisms: Evidence for a New Theory of Transformation (Academic Press: New York NY, 1977).
[47.] See “A Scientific Dissent from Darwinism” at http://www.dissentfromdarwin.org/
[48.] Joseph W. Thornton and Rob DeSalle, “Gene Family Evolution and Homology: Genomics Meets Phylogenetics,” Annual Review of Genomics and Human Genetics, 1:41-73 (2000).

Image source: repphotos/Flickr.

Casey Luskin

Associate Director and Senior Fellow, Center for Science and Culture
Casey Luskin is a geologist and an attorney with graduate degrees in science and law, giving him expertise in both the scientific and legal dimensions of the debate over evolution. He earned his PhD in Geology from the University of Johannesburg, and BS and MS degrees in Earth Sciences from the University of California, San Diego, where he studied evolution extensively at both the graduate and undergraduate levels. His law degree is from the University of San Diego, where he focused his studies on First Amendment law, education law, and environmental law.



__k-reviewContinuing SeriesMore than MythscienceTop 10