On Developmental Gene Regulatory Networks, the Scientific Literature Supports Stephen Meyer
In a post yesterday we saw that Stephen Meyer wrote extensively about evo-devo in Darwin’s Doubt, effectively answering biologist Gerd Müller’s preferred evolutionary model for how new body plans arise. If I could boil down Meyer’s arguments to three points, they would be:
Evo-devo focuses on the role of special early-acting mutations in developmental processes to generate new body plans, but over 100 years of mutagenesis experiments show that mutations in genes regulating development are invariably deleterious (or in some cases have only trivial effects). Meyer summarizes: “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.”
We see these deleterious effects particularly in experiments on developmental gene regulatory networks (dGRNs), complex networks of gene-interaction which regulate the expression of genes early in development as an organism’s body plan begins to grow. After reviewing experimental work on dGRNs, Meyer finds that, “These dGRNs cannot vary without causing catastrophic effects to the organism.”
These experimental results on dGRNS have profound implications for organismal evolution, because if changes to dGRNs are lethal to an embryo, how can they be modified to explain how new body plans evolve? Meyer’s writes in the book: “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?” (Darwin’s Doubt, p. 269)
Gerd Müller is aware that Meyer has talked about dGRNs, because Meyer mentioned them (albeit briefly) on the Joe Rogan podcast last year, and Müller even made a comment in response, saying: “he [Meyer] mentions gene regulatory networks but stops short of making the obvious argument that mutations in these gene regulatory networks you don’t need so many random mutations to create an important change of the phenotype.” But if Meyer is correct then random mutations in dGRNs are lethal to the embryo
The Literature Supports Meyer’s Arguments
Meyer was justified in making these arguments. The work of the late Caltech developmental biologist Eric Davidson, an eminent expert in the field of evo-devo, shows that mutations in genes that affect body plan characteristics (which tend to be expressed early, as the body plan is being put in place) don’t lead to new body plans — they lead to dead embryos. Meyer wrote about Davidson in Darwin’s Doubt, as we saw yesterday. But it’s worth providing some more expansive background in Davidson’s own words:
[T]here is a high penalty to change [in dGRNs], in that interference with the dynamic expression of any one of the genes causes the collapse of expression of all, and the total loss from the system of their contributions to the regulatory state … 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.
[…]
A few years ago remarkably conserved subcircuits, termed network “kernels” that operate high in the dGRN hierarchy were discovered. … the kernels similarly canalize downstream developmental process in each member of each given clade.
[…]
Evolutionary inflexibility due to highly conserved canalizing dGRN kernels
As discussed above these subcircuits operate at upper levels of dGRN hierarchy so as to affect characters of the body plan that are definitive for upper level taxa, i.e., they control the early stages of just the types of developmental process of which the invariance per taxon constitutes our problem. Since they preclude developmental alternatives, they may act to “booleanize” the evolutionary selective process: either body part specification works the way it is supposed to or the animal fails to generate the body part and does not exist.
ERIC DAVIDSON, “EVOLUTIONARY BIOSCIENCE AS REGULATORY SYSTEMS BIOLOGY,” DEVELOPMENTAL BIOLOGY, 357:35-40 (2011)
Or this
Interference with expression of any [genes in the dGRN kernel] by mutation or experimental manipulation has severe effects on the phase of development that they initiate. This accentuates the selective conservation of the whole subcircuit, on pain of developmental catastrophe.
DAVIDSON AND ERWIN. “AN INTEGRATED VIEW OF PRECAMBRIAN EUMETAZOAN EVOLUTION,” COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 74: 1-16 (2010)
This intolerance of body plan-affecting dGRNs to fundamental perturbations indicates that they could not have evolved by undirected mutations. Many coordinated mutations would be needed to convert one functional dGRN that generates a particular body plan into a different dGRN that generates a different body plan.
The classic rejoinder
Meyer is also well aware of what evo-devo proponents say in response to these arguments and he has a ready rebuttal. The classic rejoinder from evo-devo proponents is to propose that perhaps in the past somehow dGRNs were more “labile” or “flexible” and easier to evolve. Indeed, Davidson acknowledges that something must have been different when body plans first evolved, which removed this resistance to change:
Deconstructing the evolutionary process by which stem group body plans were stepwise formulated will require us to traverse the conceptual pathway to dGRN elegance, beginning where no modern dGRN provides a model. The basic control features of the initial dGRNs of the Precambrian and early Cambrian must have differed in fundamental respects from those now being unraveled in our laboratories. The earliest ones were likely hierarchically shallow rather than deep, so that in the beginning adaptive selection could operate in a larger portion of their linkages. Furthermore, we can deduce that the outputs of their sub-circuits must have been polyfunctional rather than finely divided and functionally dedicated, as in modern crown group dGRNs….
ERIC DAVIDSON, “EVOLUTIONARY BIOSCIENCE AS REGULATORY SYSTEMS BIOLOGY,” DEVELOPMENTAL BIOLOGY, FEBRUARY 2011
Davidson says there that “no modern dGRN provides a model” for how new dGRNs might evolve. Therefore he believes that, when new body plans arose, dGRNs “must have differed in fundamental respects from those now being unraveled in our laboratories.” Davidson is not the only evolutionary scientist to use this form of argument. Paleontologist Charles Marshall said much the same in 2013 when responding in the journal Science to Meyer’s arguments in Darwin’s Doubt regarding dGRNs. Marshall argued that although Meyer is correct to observe that “manipulation of such networks is typically lethal,” this is not a problem for evolution because “GRNs at the time of the emergence of the phyla were not so encumbered.” Indeed, Müller’s intermediary, Forest Valkai, makes a similar (though less eloquently stated) argument in the video attacking Meyer.
But how does Marshall or Valkai or anyone know that dGRNs were so different in the past? Similarly, how does Davidson know that early dGRNs “must have differed in fundamental respects” from those we observe? Do they know this from experiments and direct observation, or from evolutionary theory itself? The answer is evolution; more precisely, the common descent of the animals. If the animal phyla shared a common ancestor that was itself a developing species, dGRNs of the past must have been more “flexible” or “labile” — totally unlike what we observe today.
But would such a flexible or labile dGRN actually produce a viable animal? We don’t know, because we have no observational evidence. As such, to salvage evo-devo models of evolution from the contrary experimental data, Davidson and Marshall reverse the normal method of historical sciences. Present-day observations are no longer the key to the past. Rather, a theoretical model dictates what must have happened in the past — even if that model contradicts what we know from the evidence. Meyer put it this way in the Epilogue to Darwin’s Doubt
By ignoring this evidence, Marshall and other defenders of evolutionary theory reverse the epistemological priority of the historical scientific method as pioneered by Charles Lyell, Charles Darwin, and others. Rather than treating our present experimentally based knowledge as the key to evaluating the plausibility of theories about the past, Marshall uses an evolutionary assumption about what must have happened in the past (transmutation) to justify disregarding experimental observations of what does, and does not, occur in biological systems. The requirements of evolutionary doctrine thus trump our observations about how nature and living organisms actually behave. What we know best from observation takes a backseat to prior beliefs about how life must have arisen.
What we do know from experience, however, is that large increases in functionally specified information — especially information expressed in an alphabetic or digital form — are always produced by conscious and rational agents. So the best explanation for the explosion of information necessary to produce the Cambrian animals (whether that explosion occurred during or before the Cambrian period) remains intelligent design.
DARWIN’S DOUBT, P. 448
What this means is that although evo-devo has some interesting ideas, evolutionary biology currently lacks a model that is validated by experimental evidence showing that dGRNs — and hence body plans — are mutable and capable of evolving from one form to another.
More Evo-Devo Problems
But Meyer isn’t done recounting problems with evo-devo-based models of evolution. In Darwin’s Doubt he offers additional reasons why mutations in Hox genes can’t build new body structures:
Third, Hox genes only provide information for building proteins that function as switches that turn other genes on and off. The genes that they regulate contain information for building proteins that form the parts of other structures and organs. The Hox genes themselves, however, do not contain information for building these structural parts. In other words, mutations in Hox genes do not have all the genetic information necessary to generate new tissues, organs, or body plans.
Nevertheless, Schwartz argues that biologists can explain complex structures such as the eye just by invoking Hox mutations alone. He asserts that “[t]here are homeobox genes for eye formation and that when one of them, the Rx gene in particular, is activated in the right place and at the right time, an individual has an eye.” He also thinks that mutations in Hox genes help arrange organs to form body plans.
In a review of Schwartz’s book, Eörs Szathmáry finds Schwartz’s reasoning deficient. He too notes that Hox genes don’t code for the proteins out of which body parts are made. It follows, he insists, that mutations in Hoxgenes cannot by themselves build new body parts or body plans. As he explains, “Schwartz ignores the fact that homeobox genes are selector genes. They can do nothing if the genes regulated by them are not there.” Though Schwartz says he has “marveled” at “the importance of homeobox genes in helping us to understand the basics of evolutionary change,” Szathmáry doubts that mutations in these genes have much creative power. After asking whether Schwartz succeeds in explaining the origin of new forms of life by appealing to mutations in Hox genes, Szathmáry concludes, “I’m afraid that, in general, he does not.”
Nor, of course, do Hox genes possess the epigenetic information necessary for body-plan formation. Indeed, even in the best of cases mutations in Hox genes still only alter genes. Mutations in Hox genes can only generate new genetic information in DNA. They do not, and cannot, generate epigenetic information.
Instead, epigenetic information and structures actually determine the function of many Hox genes, and not the reverse. This can be seen when the same Hox gene (as determined by nucleotide sequence homology) regulates the development of different anatomical features found in different phyla. For instance, in arthropods the Hox gene Distal-less is required for the normal development of jointed arthropod legs. But in vertebrates a homologous gene (e.g., the Dlx gene in mice) builds a different kind of (nonhomologous) leg. Another homologue of the Distal-less gene in echinoderms regulates the development of tube feet and spines — anatomical features classically thought not to be homologous to arthropod limbs, nor to limbs of tetrapods. In each case, the Distal-less homologues play different roles determined by the higher-level organismal context. And since mutations in Hox genes do not alter higher-level epigenetic contexts, they cannot explain the origin of the novel epigenetic information and structure that establishes the context and that is necessary to building a new animal body plan.
DARWIN’S DOUBT, PP. 320-321
What we see from the passage quoted above, as well as from Meyer’s extensive discussion of evo-devo in Darwin’s Doubt, is that Gerd Müller is far from correct in comparing Meyer to a “gene reductionist” who thinks that only mutations in genes are needed to evolve new types of organisms. In contrast, Meyer is well aware of non-neo-Darwinian models of organismal evolution like evo-devo, which focus on the role of mutations in changing regulatory networks of genes to generate radically new body plans. Meyer also explores how non-genetic or epigenetic information is necessary to generate new body plans, and how evolutionary models seem unable to produce this information as well.
In sum, Meyer has offered extensive arguments about evo-devo generally, and in particular about dGRNs. He shows that dGRNs can’t change significantly without development shutting down, which means that there is a problem with finding mutations that can suddenly produce large-scale changes to radically alter the body plan of an organism. Since all evolution requires change, this problem applies across the board to all evolutionary claims about the origin of new body plans, not just neo-Darwinian models. The Joe Rogan podcast last year only afforded the opportunity to scratch the surface, but it’s clear that Meyer has a lot to say and that Müller really has not responded to him in any relevant detail
An Invitation to Dialogue
As a fifth and final point, we would love to hear what Professor Müller thinks of all of this. Clearly, Meyer has invested a lot of time and energy into addressing Müller’s field of evo-devo and has developed detailed, careful arguments about the viability of evo-devo-based models. I would welcome a response from Professor Müller. However, I think that our website, Evolution News, would be a better place for dialogue than Professor Müller’s responding indirectly through an angry YouTuber’s channel, with all the personal attacks and other distasteful antics that go with that particular venue. Müller deserves better.
We would be happy to host such a dialogue here at Evolution News, and I therefore invite Professor Müller to send us a robust response to Stephen Meyer’s arguments about evo-devo models of evolution. In that way, real progress can be made in this conversation
