Darwin's Doubt

by Stephen C. Meyer

  What does all this have to do with the origin of animals and the Cambrian explosion? Evolutionary biologists think that the ancestral groups of the Cambrian animals would likely have existed in relatively small populations. Lynch argues that in small populations, animal genomes will inevitably grow over time as nonprotein-coding sections of DNA (as well as gene duplicates) accumulate due to the weakness of natural selection. He thinks these neutral mutations drive the evolution and growth of genomic and phenotypic complexity in animals. In short, Lynch attempts to explain the expansion of the genome and the origin of anatomical complexity as the result of neutral, nonadaptive processes of genetic accretion, rather than as an adaptive process involving natural selection acting on random mutations. As he states, “Many of the unique complexities of the eukaryotic gene arose by semi-neutral processes with little, if any, direct involvement of positive selection.”38

  In his work, Lynch has also advanced a powerful mathematical critique of the efficacy of the neo-Darwinian mechanism. He has argued that natural selection plays a lesser role in shaping the features of evolving populations than many evolutionary theorists have previously assumed—especially in the case of relatively small populations. Lynch has argued, instead, that random environmental factors—an organism being in the right place at the right time (near an abundant food source, for example) or in the wrong place at the wrong time (in a drought-stricken region or near an erupting volcano, for example)—will play a more important role in determining reproductive success than variations in the fitness of organisms within the same population.

  CounterIntuitive Approach

  Lynch develops his mathematical critique of the creative power of natural selection based on the principles of population genetics. Nevertheless, it does not follow from his analysis showing the weakness of natural selection that neutral processes alone are sufficient to build new functional genes and proteins. Nor does it follow that neutral processes alone can account for the many complex anatomical systems that require new sources of genetic (and epigenetic) information for their construction. Indeed, it may seem counterintuitive, at least from a neo-Darwinian point of view, to think that the accumulation of random mutations alone can accomplish what neo-Darwinists have long invoked both mutations and natural selection to do. In effect, Lynch’s theory attempts to explain the origin of anatomical complexity by reference to what would seem on its face to be a less—not a more—potent mechanism than the one offered by neo-Darwinism. Could such a counterintuitive theory be correct?

  Perhaps, but as a comprehensive theory of how biological information and anatomical complexity arises, Lynch’s neutral theory leaves much to be desired.

  In the first place, Lynch’s theory offers no explanation for some of the crucial molecular machinery present in eukaryotes—machinery that is necessary to rendering his mechanism for the accumulation and subsequent expression of genetic information credible. Recall that Lynch thinks that small populations of multicellular organisms in particular would have inevitably accumulated many insertional genomic elements. But for the functional information in these growing genomes to be expressed, the cell must have some way of excising the nonfunctional randomly accreting genetic elements—at least, until some of them mutate to the point that they contribute to producing functional genes and proteins.

  Extant eukaryotic organisms depend on a sophisticated molecular machine called a spliceosome—a machine that excises introns and fuses together exons (the portions of the genome that code for proteins) before gene expression takes place. “This large complex,” observes cell biologist Melissa Jurica, is “composed of over 150 individual proteins” and several structural RNAs, and thus “may indeed deserve the moniker ‘the most complicated macromolecular machine in the cell.’ ”39

  So where do spliceosomes, and the genes necessary to produce them, come from? Lynch doesn’t say, though he recognizes, of course, the importance of this molecular machinery to gene expression and to his scenario. As he explains, “The problem is that introns are inside genes and get transcribed to mRNA but then have to be spliced out perfectly. If you’re one nucleotide off, you get a dead transcript.”40 Nevertheless, Lynch’s theory presupposes, but does not explain, the origin of the genetic information necessary to produce the spliceosomes that perform this function. He certainly does not explain the origin of these massive multiprotein, multi-RNA complexes by reference to any neutral evolutionary process. Nor can he, since his theory of genomic accretion and expression presupposes the existence of precisely such intricate machines. Instead, as my colleague Paul Nelson has put it rather colorfully, “to get Lynch’s theory of genomic accretion up and running, a great deal of complicated molecular machinery must be rolled in from offstage.”

  Of course, it could be argued that these machines and systems arose much earlier with the origin of the eukaryotic cell as the result of selection-driven evolution in the large populations of simpler unicellular organisms in which, according to Lynch’s theory, natural selection played a more significant role. Nevertheless, Lynch does not make that argument—and for good reason. Most evolutionary biologists today recognize the origin of the eukaryotic cell as a completely unsolved problem—unexplained by either neutral or adaptive theories of evolution.41

  Of course, insofar as these molecular machines are present in even one-celled eukaryotic organisms, they would have arisen, presumably, well before the origin of animals. Thus, explaining their origin is not, strictly speaking, directly relevant to explaining the Cambrian explosion. Nevertheless, Lynch’s inability to account for their origin reflects directly on the credibility of his theory—at least insofar as it seeks to offer a comprehensive account of the mechanisms by which biological information and complexity arise during the history of life.

  Drifting In and Out

  In any case, there are good reasons to doubt that Lynch’s neutral mechanism could generate the novel biological information and form necessary to explain the origin of animals, even granting the prior existence of the molecular machinery (in small populations of eukaryotic organisms) that his scenario requires.

  First, Lynch assumes a false gene-centric view of the origin of biological form. As he writes: “Most of the phenotypic diversity that we perceive in the natural world is directly attributable to the peculiar structure of the eukaryotic gene.”42 His view overlooks the crucial role of epigenetic information and structure in the origin of animal form discussed in Chapter 14 and, therefore, does nothing to explain its origin.

  Second, neutral processes such as genetic drift do not favor beneficial mutations, and thus do not fix, with any efficiency, those mutation-induced genetic traits in small populations.43 Natural selection, as we saw in Chapter 10, is something of a double-edged sword. On the one hand, natural selection helps to fix beneficial traits in a population. On the other hand, natural selection also makes it difficult for functional genes to vary widely without being eliminated. Neutral theories of evolution attempt to avoid the latter problem by invoking gene duplication and other processes that can add nonfunctional sequences to the genome—sequences that are unaffected, at least initially, by selective pressure. In so doing, however, these theoretical formulations significantly diminish the role of natural selection as a mechanism that can fix beneficial mutations in place once they have arisen. Thus, in all neutral theories, including Lynch’s, any beneficial mutations that arise and begin to drift through a population, can just as readily—without a significant influence from natural selection to impede it—drift out of a population as well. This limitation vastly increases the time it will take for neutral processes to fix beneficial genetic changes in a population. Both skeptics and proponents of neo-Darwinism have recognized this deficiency in Lynch’s model.44

  Third, and most important, Lynch’s theory not only fails to account for the fixation of new genes and traits in small populations, it also fails to account for their origin. Lynch’s mechanism of neutral mutational change does envision the addit
ion of brute genomic complexity as the result of the accretion of preexisting genetic elements (introns, transposons, pseudogenes and gene duplicates). Nevertheless, the addition of these elements does not generate any novel functional (or specified) genetic information. Instead, it merely transfers preexisting genetic sequences from one organismal context where those sequences may have performed a function, to another where they likely will not. Indeed, the point of neutral theory is to postulate the addition of genetic elements that, initially, do not perform crucial functions such that they can experience mutations without deleterious consequence to the organism. Lynch himself assumes that these added elements will not perform functions in their new context, which is why he envisions the need for spliceosomes to excise them, at least initially.

  Instead, for Lynch’s theory to explain the origin of new and functional genes and proteins (and the anatomical complexities that depend on them), his theory would have to solve the problem of combinatorial inflation discussed in Chapter 10. He would have to show that purely random mutations could efficiently search the relevant combinatorial space of possible sequences corresponding to a given novel functional gene or protein.

  Nevertheless, Lynch does not even address the problem of combinatorial inflation or the closely related problem of the rarity of genes and proteins in sequence space. He provides no experimental evidence that recombination and/or mutation (given genetic drift) will actually produce functional or specified genetic complexity. Instead, the examples he provides are entirely hypothetical. In addition, he offers no reason to think that the probability of a successful search for functional genes or proteins would be any higher (i.e., more likely to occur) than the probabilities calculated in Chapter 10. He does not, therefore, answer the challenge of the problem of combinatorial inflation and the rarity of functional genes and proteins in sequence space.

  Lynch does provide, perhaps, a more detailed characterization than other neutral theories of where neutral, nonadaptive processes must predominate. Nevertheless, he does not show that such processes—random genetic mutations unhinged from natural selection—are sufficient to generate novel functional genes and proteins, let alone complex anatomical novelties requiring the origin of many such genes and proteins. Instead, as Axe’s experimental results have shown, random mutations of whatever kind will not generate enough trials to render probable (or plausible) a successful search of the sequence space corresponding to a given functional gene or protein.

  Lynch and Waiting Times

  Lynch does argue in one paper that neutral evolutionary processes can generate new complex adaptations—adaptations requiring multiple coordinated mutations—within realistic waiting times. In particular, writing in a recent paper with colleague Adam Abegg of St. Louis University, he argues that “conventional population genetic mechanisms” such as random mutation and genetic drift can cause the “relatively rapid emergence of specific complex adaptations.”45 Lynch makes two specific claims in this regard. First, he claims that in large populations, arbitrarily complex adaptations can occur if the mutational intermediates are neutral in their effects on the organism. That is, Lynch purports to show that in large microbial populations, complex adaptations requiring a virtually unlimited number of mutations can occur within realistic waiting times. According to Lynch, this can occur provided that each mutation in a series of mutations has neutral (but not deleterious) effects on the organism. Second, Lynch argues that even though it generally takes longer to build complex traits in small populations, such traits can still evolve within realistic waiting times provided, again, that the mutational intermediates are neutral in their effects. In fact, he concludes that “the elevated power of both random genetic drift and mutation may enable the acquisition of complex adaptations in multicellular species at rates that are not appreciably different from those achievable in enormous microbial populations.”46

  Though Lynch makes these assertions in the context of a densely mathematical scientific article, the significance of his claims, if true, can hardly be overstated. In essence, he claims that his population genetics–based mathematical model shows that purely random mutations and genetic drift can generate extremely complex adaptations in realistic waiting times—that his neutral evolutionary theory solves the problem of complex adaptations and long expected waiting times discussed in Chapter 12.

  But some things are just too good to be true, and it turns out that Lynch and Abegg made a subtle but fundamental mathematical error in coming to their conclusion. Appropriately, perhaps, the first person to demonstrate that Lynch’s incredible claim was problematic was Douglas Axe. Although Axe could see that much of the math in Lynch’s paper with Abegg was correct, Axe suspected from his own calculations and experiments that they had made some crucial error. In the end, he traced Lynch and Abegg’s claims to two erroneous equations, both of which were based on an erroneous assumption. In essence, Lynch and Abegg assumed that organisms will acquire a given complex adaptation by traversing a direct path to the new anatomical structure. Each mutation would build on the previous one in the most efficient manner possible—with no setbacks, false starts, aimless wandering, or genetic degradation—until the desired structure or system (or gene) is constructed. Thus, they formulated an undirected model of evolutionary change, and one that assumes, moreover, that there is no mechanism available (such as natural selection) that can lock in potentially favorable mutational changes on the way to some complex advantageous structure. Nevertheless, they calculated the waiting times required to produce such structures as if a process for locking in potentially advantageous changes did exist, and as if their undirected and purely random mechanism was in some way directed to these functionally propitious outcomes. As Axe notes in a trenchant mathematical critique of Lynch and Abegg’s argument, “Of all the possible evolutionary paths a population can take, the analysis of Lynch and Abegg considers only those special paths that lead directly to the desired end—the complex adaptation.”47

  Yet nothing in Lynch’s neutral model ensures that potentially advantageous mutations will remain in place while other mutations accrue. As Axe explains, “Productive changes cannot be ‘banked’, whereas Equation 2 [one of Lynch’s equations] presupposes that they can.”48 Instead, Axe shows, mathematically, that degradation (the fixation of mutational changes that make the complex adaptation less likely to arise) will occur much more rapidly than constructive mutations, causing the expected waiting time to increase exponentially.

  The illustration I developed in Chapter 10 to explain the problem facing neutral models of gene evolution may help illuminate the mistaken assumption underlying Lynch and Abegg’s calculations. Recall from that chapter that my hypothetical blindfolded man dropped in the middle of an enormous shark-free pool did not face any predators (by analogy the purifying effects of natural selection). But he still faced the problem of finding the ladder at the edge of the enormous body of water (by analogy, the need to search an enormous number of possible mutational paths and possible sequences to find the rare functional ones). Now suppose someone were to calculate how long on average it would take for the blindfolded man to swim to the ladder at the edge of the enormous pool. If someone simply divided the distance to the ladder at the edge of the pool by the maximum speed that man could swim, he or she would get a fantastically optimistic estimate of the severity of the problem facing our unfortunate swimmer. Why? Because calculating the probable waiting time in this manner would overlook the main problem the man faced, namely, the man does not know where the ladder is or how to get there. Nor does he have any way to gauge his progress.

  Thus, any realistic estimate of how long it will actually take him to swim to the ladder—as opposed to an estimate of the theoretically fastest route possible—must take into account his probable aimless wandering, fits and starts, swimming in circles and drifting in various directions. Similarly, Lynch and Abegg fail to reckon in their calculation on the random, undirected and, literally, aimless nature of the mech
anism that they propose. Instead, they mistakenly assume that neutral processes of evolution will make a beeline for some specific complex adaption. In fact, these processes will—in all probability—also wander aimlessly in a vast sequence space of neutral, functionless possibilities with nothing to direct them, or preserve them in any forward progress they happen to make, toward the rare and isolated islands of function represented by complex adaptations. For this reason, Lynch vastly underestimates the waiting times required to generate complex adaptations and, therefore, does not solve the problem of the origin of genes and proteins or any other complex adaptation. Instead, Axe shows in his own mathematical model, which accompanies his critique of Lynch, that the waiting times problem is just as severe as he (Axe) had previously calculated.

  Neo-Lamarckian Epigenetic Inheritance

  The third element of the neo-Darwinian triad concerns the transmission and inheritance of genetic information. Not surprisingly, a new version of evolutionary theory questions the neo-Darwinian understanding of heredity as well.

  Darwin himself lacked an accurate theory of how features of organisms are transmitted from one generation to the next. He thought that changes in organisms that occurred during their lifetimes, as the result of the “use and disuse” of different organs and anatomical systems, would be transmitted to offspring through reproduction.49 In this respect, his theory of inheritance resembled that of an earlier evolutionary theorist, Jean-Baptiste de Lamarck (1744–1829), who also believed in the inheritance of acquired characteristics.