Evolution
Intelligent Design
Stephen Meyer’s Extensive Treatment of Evo-Devo

Yesterday I noted that Gerd Müller, emeritus professor at the University of Vienna, had responded last year to Stephen Meyer’s points on the Joe Rogan podcast about development and evolution. Müller is a critic of neo-Darwinian theory and its ability to explain the origin of biological novelty, and instead prefers evo-devo-based models to explain how new body plans arise. While this did not come up much in the Rogan podcast, Meyer in Darwin’s Doubt actually wrote quite a bit about evo-devo-based models of organismal evolution.
Settle in for a Long Read
Prepare for a long read because in the book, Meyer devotes a lot of space to the subject. Here’s what he writes:
Evolutionary theorists and developmental biologists such as Rudolf Raff, Sean B. Carroll, and Wallace Arthur have developed a subdiscipline of biology known as evolutionary developmental biology, or “evo-devo” for short. The evolutionary developmental biologists have since formulated alternative models that challenge a key aspect of the neo-Darwinian triad. Whereas neo-Darwinism envisions new form arising as the result of slow, incremental accumulations of minor mutations, evolutionary developmental biologists argue that mutations affecting genes involved in animal development can cause large-scale morphological change and even whole new body plans. … One approach falls under the rubric of “evo-devo” and conceives of mutations producing modifications in larger increments.
[…]
EVO- DEVO AND ITS PROPOSALS
The neo-Darwinian synthesis has long emphasized that large-scale macroevolutionary change occurs as the inevitable by-product of the accumulation of small-scale “microevolutionary” changes within populations. The consensus in support of this idea began to fray in evolutionary biology during the early 1970s, when young paleontologists such as Gould, Niles Eldredge, and Steven Stanley realized that the fossil record did not show a pattern of gradual “micro-to-macro” change. In 1980, at a now famous symposium on macroevolution at the Field Museum in Chicago, the rebellion burst into full view, exposing what developmental biologist Scott Gilbert called “an underground current in evolutionary theory” among theorists who had concluded that “macroevolution could not be derived from microevolution.”
At the conference, paleontologists who doubted the “micro-to-macro” consensus found allies among younger developmental biologists. They were dissatisfied with neo-Darwinism in part because they knew that population genetics, its mathematical expression, sought only to quantify changes in gene frequency rather than explain the origin of genes or novel body plans. Thus, many developmental biologists thought that neo-Darwinism did not offer a compelling theory of macroevolution.
To formulate a more robust theory, many developmental biologists, such as Rudolf Raff, a developmental biologist at the University of Indiana and one of the founders of “evo-devo,” urged evolutionary theorists to incorporate insights from their discipline. For example, developmental biologists know that mutations expressed early in the development of animals are necessary to alter body-plan morphogenesis. Thus, they argue that these mutations must have played a significant role in generating whole new animal forms during the history of life. They assert that this understanding of developmental processes is crucial to understanding animal evolution. Some evo-devo advocates such as Sean B. Carroll and Jeffrey Schwartz have pointed specifically to homeotic (or Hox) genes — master regulatory genes that affect the location, timing, and expression of other genes — as entities capable of producing such large- scale change in animal form. These evo-devo advocates have broken with classical neo-Darwinism primarily in their understanding of the size or increment of mutational change.
MAJOR BUT NOT VIABLE, VIABLE BUT NOT MAJOR
Despite the enthusiasm surrounding the field, evo-devo fails, and for an obvious reason: its main proposal, that early- acting developmental mutations can cause stably heritable, large-scale changes in animal body plans, contradicts the results of one hundred years of mutagenesis experiments. As we saw in Chapter 13, the experiments of scientists such as Nüsslein-Volhard and Wieschaus have shown definitively that early-acting body-plan mutations invariably generate embryonic lethals — dead animals incapable of further evolution. Th e results of these experiments have generated the dilemma for evolutionary biologists that geneticist John McDonald aptly described as the “great Darwinian paradox.” Recall that McDonald noted that early-acting regulatory mutations do not produce viable alterations in form that will persist in populations, as evolution absolutely requires. Instead, these mutations are eliminated immediately by natural selection because of their invariably destructive consequences. On the other hand, later- acting mutations can generate viable changes in the features of animals, but these changes do not affect global animal architectures. This generates a dilemma: major changes are not viable; viable changes are not major. In neither case do the kinds of mutation that actually occur produce viable major changes of the kind necessary to build new body plans.
In 2007, I coauthored a textbook with several colleagues titled Explore Evolution. In it, we explained this “either/or” (“major-not-viable, viable-not-major”) dilemma and suggested that it posed a challenge to theories that rely on the mutation and selection mechanism to explain the origin of major morphological changes. The National Center for Science Education (NCSE) — an influential activist group that opposes allowing students to learn about scientific criticisms of evolutionary theory — challenged our critique. They charged that our textbook “fails to acknowledge the extensive research on mutations in DNA sequences that do not encode proteins, but which have important morphological effects.” In other words, they claimed that some viable mutations do produce major large-scale changes.
The NCSE cited papers from the “evo-devo” literature claiming that a type of mutation in the regulatory regions of the genome, “cis-regulatory” regions, have been shown to produce large-scale changes in winged insects. According to the NCSE, mutations in these cis-regulatory elements (or CREs) are “considered by many evolutionary biologists to have the greatest potential for generating evolutionary change.” What’s more, they insisted that “mutations in CREs play an important role in morphological evolution.” The NCSE cited a paper in the Proceedings of the National Academy of Sciences by three developmental biologists, Benjamin Prud’homme, Nicolas Gompel, and Sean B. Carroll. The paper did not show what the NCSE claimed, however. It did assert that changes in regulatory DNA produce “both relatively modest morphological differences among closely related species and more profound anatomical divergences among groups at higher taxonomical levels.” But the study only showed how changes in the cis-regulatory elements in fruit fly DNA might have affected the coloration of wing spots in several different types of flying insects. It did not report any significant change in the form or body plan of these insects. Instead, the study highlighted a clear case of a viable mutation generating merely a minor or superficial change.
Not surprisingly, many evolutionary biologists recognize that such regulatory mutations do not explain the evolution of new body plans. For example, Hopi Hoekstra, of Harvard University, and Jerry Coyne, two traditional neo-Darwinists, have published an article reviewing various evo-devo proposals in the journal Evolution. They note, “Genomic studies lend little support to the cis-regulatory theory” of evolutionary change.
They also argue, tellingly, that most cis-regulatory mutations result in the loss of genetic and anatomical traits, including a famous case in which evolutionary biologists attributed the loss of pelvic spines in stickleback fish to mutations in cis-regulatory elements. Yet, as they argue, “supporting the evo-devo claim that cis-regulatory changes are responsible for morphological innovations requires showing that promoters are important in the evolution of new traits, not just the losses of old ones.” Hoekstra and Coyne conclude, “Th ere is no evidence at present that cis-regulatory changes play a major role — much less a pre-eminent one — in adaptive evolution.” Given their commitment to neo-Darwinism, it’s fair to assume that Hoekstra and Coyne probably did not intend, in making this argument, to refute the NCSE’s criticism of our textbook Explore Evolution. Nevertheless, science, like politics, sometimes makes for strange bedfellows.
WHAT ABOUT HOX GENES?
When biology students hear my colleague Paul Nelson describe the “great Darwinian paradox” in public lectures on university campuses, they often ask, “What about Hox genes?” Recall that Hox (or homeotic) genes regulate the expression of other protein-coding genes during the process of animal development. Some biologists have likened them to the conductor of an orchestra who plays the role of coordinating the contributions of the players. And because Hox genes affect so many other genes, many evo-devo advocates think that mutations in these genes can generate large-scale changes in form.
For example, Jeffrey Schwartz, at the University of Pittsburgh, invokes mutations in Hox genes to explain the sudden appearance of animal forms in the fossil record. In his book Sudden Origins, Schwartz acknowledges the discontinuities in the fossil record. As he notes, “We are still in the dark about the origin of most major groups of organisms. They appear in the fossil record as Athena did from the head of Zeus — full-blown and raring to go, in contradiction to Darwin’s depiction of evolution as resulting from the gradual accumulation of countless infinitesimally minute variations.”
What resolves this mystery? Schwartz, an evo-devo advocate, reveals his answer: “A mutation affecting the activity of a homeobox [Hox] gene can have a profound effect — such as turning … larval tunicates into the first chordates. Clearly, the potential homeobox genes have for enacting what we call evolutionary change would seem to be almost unfathomable.”
But can mutations in Hox genes transform one form of animal life — one body plan — into another? There are several reasons to doubt that they can.
First, precisely because Hox genes coordinate the expression of so many other different genes, experimentally generated mutations in Hox genes have proven harmful. William McGinnis and Michael Kuziora, two biologists who have studied the effects of mutations on Hox genes, have observed that in fruit flies “most mutations in homeotic [Hox] genes cause fatal birth defects.” In other cases, the resulting Hox mutant phenotype, while viable in the short term, is nonetheless markedly less fit than the wild type. For example, by mutating a Hox gene in a fruit fly, biologists have produced the dramatic Antennapedia mutant, a hapless fly with legs growing out of its head where the antennae should be. Other Hox mutations have produced fruit flies in which the balancers (tiny structures behind wings that stabilize the insect in flight, called “halteres”) are transformed into an extra pair of wings. Such mutations alter the structure of the animal, but not in a beneficial or permanently heritable way. The Antennapedia mutant cannot survive in the wild; it has difficulty reproducing, and its offspring die easily. Similarly, fruit-fly mutants sporting an extra set of wings lack the musculature to make use of them and, absent their balancers, cannot fly. As Hungarian evolutionary biologist Eörs Szathmáry notes with cautious understatement in the journal Nature, “macromutations of this sort [i.e., in Hox genes] are probably frequently maladaptive.”
Second, Hox genes in all animal forms are expressed after the beginning of animal development, and well after the body plan has begun to be established. In fruit flies, by the time that Hox genes are expressed, roughly 6,000 cells have already formed, and the basic geometry of the fly — its anterior, posterior, dorsal, and ventral axes — is already well established. So Hox genes don’t determine body-plan formation. Eric Davidson and Douglas Erwin have pointed out that Hox gene expression, although necessary for correct regional or local differentiation within a body plan, occurs much later during embryogenesis than global body-plan specification itself, which is regulated by entirely different genes. Thus, the primary origin of animal body plans in the Cambrian explosion is not merely a question of Hox gene action, but of the appearance of much deeper control elements — Davidson’s “developmental gene regulatory networks” (dGRNs). And yet, as we saw in Chapter 13, Davidson argues that it is extremely difficult to alter dGRNs without damaging their ability to regulate animal development.
Darwin’s Doubt, pp. 312-320
Stephen Meyer on dGRNs
At this point it’s worth recounting what Meyer writes about dGRNs in Chapter 13 of Darwin’s Doubt:
DEVELOPMENTAL GENE REGULATORY NETWORKS
Another line of research in developmental biology has revealed a related challenge to the creative power of the neo-Darwinian mechanism. Developmental biologists have discovered that many gene products (proteins and RNAs) needed for the development of specific animal body plans transmit signals that influence the way individual cells develop and differentiate themselves. Additionally, these signals affect how cells are organized and interact with each other during embryological development. These signaling molecules influence each other to form circuits or networks of coordinated interaction, much like integrated circuits on a circuit-board. For example, exactly when a signaling molecule gets transmitted often depends upon when a signal from another molecule is received, which in turn affects the transmission of still others — all of which are coordinated and integrated to perform specific time-critical functions. The coordination and integration of these signaling molecules in cells ensures the proper differentiation and organization of distinct cell types during the development of an animal body plan. Consequently, just as mutating an individual regulatory gene early in the development of an animal will inevitably shut down development, so too will mutations or alterations in the whole network of interacting signaling molecules destroy a developing embryo.
No biologist has explored the regulatory logic of animal development more deeply than Eric Davidson, at the California Institute of Technology. Early in his career, collaborating with molecular biologist Roy Britten, Davidson formulated a theory of “gene regulation for higher cells.” By “higher cells” Davidson and Britten meant the differentiated, or specialized, cells found in any animal aft er the earliest stages of embryological development. Davidson observed that the cells of an individual animal, no matter how varied in form or function, “generally contain identical genomes.” During the life cycle of an organism, the genomes of these specialized cells express only a small fraction of their DNA at any given time and produce different RNAs as a result. These facts strongly suggest that some animal-wide system of genetic control functions to turn specific genes on and off as needed throughout the life of the organism — and that such a system functions during the development of an animal from egg to adult as different cell types are being constructed.
When they proposed their theory in 1969, Britten and Davidson acknowledged that “little is known . . . of the molecular mechanisms by which gene expression is controlled in differentiated cells.” Nevertheless, they deduced that such a system must be at work. Given: (1) that tens or hundreds of specialized cell types arise during the development of animals, and (2) that each cell contains the same genome, they reasoned (3) that some control system must determine which genes are expressed in different cells at different times to ensure the differentiation of different cell types from each other — some system-wide regulatory logic must oversee and coordinate the expression of the genome.
Davidson has dedicated his career to discovering and describing the mechanisms by which these systems of gene regulation and control work during embryological development. During the last two decades, research in genomics has revealed that nonprotein- coding regions of the genome control and regulate the timing of the expression of the protein-coding regions of the genome. Davidson has shown that the nonprotein-coding regions of DNA that regulate and control gene expression and the protein-coding regions of the genome together function as circuits. These circuits, which Davidson calls “developmental gene regulatory networks” (or dGRNs) control the embryological development of animals.
On arriving at Caltech in 1971, Davidson chose the purple sea urchin, Strongylocentrotus purpuratus, as his experimental model system. The biology of S. purpuratus makes it an attractive laboratory subject: the species occurs abundantly along the Pacific coast, produces enormous quantities of easily fertilized eggs in the lab, and lives for many years. Davidson and his coworkers pioneered the technology and experimental protocols required to dissect the sea urchin’s genetic regulatory system.
The remarkable complexity of what they found needs to be depicted visually. Figure 13.4a shows the urchin embryo as it appears six hours after development has begun (top left of diagram). This is the 16- cell stage, meaning that four rounds of cell division have already occurred (1 → 2 → 4 → 8 → 16). As development proceeds in the next four stages, both the number of cells and the degree of cellular specialization increases, until, at 55 hours, elements of the urchin skeleton come into focus. Figure 13.4b shows, corresponding to these drawings of embryo development, a schematic diagram with the major classes of genes (for cell and tissue types) represented as boxes, linked by control arrows. Last, Figure 13.4c shows what Davidson calls “the genetic circuitry” that turns on the specific biomineralization genes that produce the structural proteins needed to build the urchin skeleton.
This last diagram represents a developmental gene regulatory network (or dGRN), an integrated network of protein and RNA-signaling molecules responsible for the differentiation and arrangement of the specialized cells that establish the rigid skeleton of the sea urchin. Notice that, to express the biomineralization genes that produce structural proteins that make the skeleton, genes far upstream, activated many hours earlier in development, must first play their role.
This process does not happen fortuitously in the sea urchin but via highly regulated and precise control systems, as it does in all animals. Indeed, even one of the simplest animals, the worm C. elegans, possessing just over 1,000 cells as an adult, is constructed during development by dGRNs of remarkable precision and complexity. In all animals, the various dGRNs direct what Davidson describes as the embryo’s “progressive increase in complexity” — an increase, he writes, that can be measured in “informational terms.”
Davidson notes that, once established, the complexity of the dGRNs as integrated circuits makes them stubbornly resistant to mutational change — a point he has stressed in nearly every publication on the topic over the past fifteen years. “In the sea urchin embryo,” he points out, “disarming any one of these subcircuits produces some abnormality in expression.”
Developmental gene regulatory networks resist mutational change because they are organized hierarchically. This means that some developmental gene regulatory networks control other gene regulatory networks, while some influence only the individual genes and proteins under their control. At the center of this regulatory hierarchy are the regulatory networks that specify the axis and global form of the animal body plan during development. These dGRNs cannot vary without causing catastrophic effects to the organism.
Indeed, there are no examples of these deeply entrenched, functionally critical circuits varying at all. At the periphery of the hierarchy are gene regulatory networks that specify the arrangements for smaller-scale features that can sometimes vary. Yet, to produce a new body plan requires altering the axis and global form of the animal. This requires mutating the very circuits that do not vary without catastrophic effects. As Davidson emphasizes, mutations affecting the dGRNs that regulate body-plan development lead to “catastrophic loss of the body part or loss of viability altogether.” He explains in more detail:
“There is always an observable consequence if a dGRN subcircuit is interrupted. Since these consequences are always catastrophically bad, flexibility is minimal, and since the subcircuits are all interconnected, the whole network partakes of the quality that there is only one way for things to work. And indeed the embryos of each species develop in only one way.”
ENGINEERING CONSTRAINTS
Davidson’s findings present a profound challenge to the adequacy of the neo-Darwinian mechanism. Building a new animal body plan requires not just new genes and proteins, but new dGRNs. But to build a new dGRN from a preexisting dGRN by mutation and selection necessarily requires altering the preexisting developmental gene regulatory network (the very kind of change that, as we saw in Chapter 12, cannot arise without multiple coordinated mutations). In any case, Davidson’s work has also shown that such alterations inevitably have catastrophic consequences.
Davidson’s work highlights a profound contradiction between the neo-Darwinian account of how new animal body plans are built and one of the most basic principles of engineering — the principle of constraints. Engineers have long understood that the more functionally integrated system is, the more difficult it is to change any part of it without damaging or destroying the system as a whole. Davidson’s work confirms that this principle applies to developing organisms in spades. The system of gene regulation that controls animal-body-plan development is exquisitely integrated, so that significant alterations in these gene regulatory networks inevitably damage or destroy the developing animal. But given this, how could a new animal body plan, and the new dGRNs necessary to produce it, ever evolve gradually via mutation and selection from a preexisting body plan and set of dGRNs?
Davidson makes clear that no one really knows: “contrary to classical evolution theory, the processes that drive the small changes observed as species diverge cannot be taken as models for the evolution of the body plans of animals.” He elaborates:
“Neo-Darwinian evolution . . . assumes that all process works the same way, so that evolution of enzymes or flower colors can be used as current proxies for study of evolution of the body plan. It erroneously assumes that change in protein- coding sequence is the basic cause of change in developmental program; and it erroneously assumes that evolutionary change in body-plan morphology occurs by a continuous process. All of these assumptions are basically counterfactual. This cannot be surprising, since the neo-Darwinian synthesis from which these ideas stem was a premolecular biology concoction focused on population genetics and … natural history, neither of which have any direct mechanistic import for the genomic regulatory systems that drive embryonic development of the body plan.”
Darwin’s Doubt, pp. 264-269