Structure of a gene regulatory network. Image courtesy of Wikipedia.
In a series of three articles (see here, here and here) over at Evolution News and Views, Dr. Casey Luskin, a geologist and an attorney who is also an Associate Director and Senior of the Center for Science and Culture, recently discussed the question of whether mutations in gene regulatory networks are capable of giving rise to significant changes in phenotype. Dr. Luskin argued that unguided processes, be they microevolutionary (i..e. neo-Darwinian) or macroevolutionary, are simply unable to account for the evolution of new body plans.
Dr. Luskin’s articles were irenic in tone and commendably fair in their discussion of opposing views. The author’s style of exposition was also admirably lucid. However, what struck me most about the articles was their use of dated sources. Reading them, I felt like I was stepping back in time.
The TARDIS (a time machine in the Doctor Who series) as it looked between 2005 and 2010, on display at BBC Television Centre. Image courtesy of zir.com and Wikipedia.
Dr. Luskin’s first article quoted from three works that were either edited or authored by biologist Gerd Müller, emeritus professor at the University of Vienna. The first of these was a 2003 MIT Press book he co-edited with Stuart Newman, titled, Origination of Organismal Form: Beyond the Gene in Developmental and Evolutionary Biology, in which he bemoaned the fact that neo-Darwinism has “no theory of the generative,” since it dodges the question of “the origination of phenotypic traits and of organismal form.” The second was the 2010 volume Evolution: The Extended Synthesis, which Müller co-edited with Massimo Pigliucci, in which Müller heavily criticized the evolutionary Modern Synthesis of the early 20th century for failing to address “the problem of how complex morphological traits originate and how specific combinations of traits become stabilized as body plans,” while at the same time enthusiastically hailing evolutionary developmental biology (known informally as evo-devo) for enabling researchers to start tackling “a suite of problems at the phenotype level of evolution,” such as “the origin of structural complexity, … rapid change of form, and … the problem of innovation.” The third was a lecture at the 2016 meeting of the Royal Society, in which Müller pointed out that the neo-Darwinian model is “not designed” for addressing questions such as the origin of new body plans or novel characters, since it is “focused on characters that exist already and their variation and maintenance across populations, but not on how they originate.”
The second article by Dr. Luskin consisted almost entirely of lengthy quotations from chapters 13 and 16 of Darwin’s Doubt, a best-selling by leading ID proponent Dr. Stephen Meyer, which argued that intelligent design was the best explanation for the origin of new body plans in animals. Dr. Meyer’s book was published by HarperCollins in 2013.
The final article by Dr. Luskin quoted from two articles authored or co-authored by Professor Eric Davidson, a Caltech developmental biologist and an eminent expert in the field of evo-devo, who spent much of his career trying to understand how animal embryos develop, at the genetic level. In citing Davidson’s works, Luskin endeavored to provide support for Dr. Meyer’s claim that experiments on developmental gene regulatory networks (dGRNs), which “consist of the regulatory and signaling genes that drive any given process of development and the functional interactions among them” [Davidson and Levine, 2008] had demonstrated that “[t]hese dGRNs cannot vary without causing catastrophic effects to the organism” (Meyer, 2013, p. 268). The two articles cited by Luskin were written in 2010 and 2011. In his 2011 article, Davidson proposed that “[t]he 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,” enabling mutations to occur in these networks without leading to invariably fatal consequences for the developing embryo – a hypothesis ridiculed by Dr. Meyer as baseless and ad hoc. Professor Davidson passed away in 2015, shortly after the publication of his magnum opus, which he co-authored with Caltech Assistant Research Professor Isabelle S. Peter.
Can anyone spot the pattern here? The works cited are all at least eight years old, and some of them are considerably older. Dr. Luskin has made no attempt to ascertain whether recent research backs up Dr. Meyer’s sweeping claim that developmental gene regulatory networks (dGRNs) “cannot vary without causing catastrophic effects to the organism.”
Davidson overturns Davidson, using sea urchins
Professor Eric Davidson was highly acclaimed in scientific circles for leading the effort to sequence the genome of the purple sea urchin, Strongylocentrotus purpuratus. In 2022, seven years after his death, a team led by Professor Greg Wray published an article titled, “Recent reconfiguration of an ancient developmental gene regulatory network in Heliocidaris sea urchins” (Nature Ecology and Evolution 6, 1907–1920 (2022)), which investigated two species of sea urchin belonging to another genus, Heliocidaris, whose life histories were strikingly different. Comparing the two species, the team uncovered “profound evolutionary changes to early embryonic patterning events, disrupting regulatory interactions previously conserved for ~225 million years.” The team’s conclusions are worth quoting (all bolding below is mine – VJT):
These results demonstrate that natural selection can rapidly reshape developmental gene expression on a broad scale when selective regimes abruptly change. More broadly, even highly conserved dGRNs and patterning mechanisms in the early embryo remain evolvable under appropriate ecological circumstances.
The lead author of the paper was Dr. Phillip Davidson, a former graduate student in Professor Wray’s lab who is now a postdoc at Indiana University. In a wide-ranging interview with Alissa Kocer of the Duke University School of Medicine, Dr. Davidson discussed the significance of his team’s work. He begins by outlining two rival hypotheses regarding how the development of animal embryos might evolve over the course of time:
Early embryogenesis is a critical point in multicellular development as it is the stage when many specification and patterning events are decided. As a result, researchers predict that early embryonic processes and genetic interactions are deeply conserved among related species given their importance for development. But several examples exist across the tree of life that appear to defy this rule.
There are two hypotheses regarding how early development may evolve. On the one hand, gene networks responsible for carrying out embryogenesis could evolve quickly to generate new phenotypes, even though these changes would normally be too detrimental to be maintained in a population. Alternatively, these gene networks could remain stable during embryonic evolution, and instead maternally-provisioned biomolecules, like proteins, mRNA, and lipids that are deposited into eggs during oogenesis are responsible for developmental changes and mask the underlying gene network.
We wanted to address these hypotheses by comparing the genomes, transcriptomes, and epigenomes of sea urchin species with highly divergent early embryonic programs and life histories: Heliocidaris erythrogramma (non-feeding larvae, derived condition) and Heliocidaris tuberculata (feeding larvae, ancestral condition).
(It is worth noting that the two species diverged relatively recently: a mere 4 to 7 million years ago. We are not talking about the Cambrian period here. The developmental gene regulating network of the species representing the ancestral form can be seen here , while that of the species representing the derived form can be seen here.)
The team’s findings were highly revealing:
We found the sequence and accessibility of many non-coding regions regulating gene expression has evolved in H. erythrogramma, and specification of cell types is highly delayed. Furthermore, genes composing the larval skeletogenic subnetwork in this species have been either lost or acquired alternative functions, which suggests a dramatic modification to sea urchin developmental gene regulatory network.
The upshot of this research is that rapid and radical evolution of dGRNs can and does occur in nature:
This research provides a concrete example of how early genetic interactions can rapidly evolve over short timescales to produce radical changes in body patterning and trait development. Instead of assuming early development is a developmental stage burdened with conserved, immutable genetic interactions, this study demonstrates even embryogenesis remains evolvable under appropriate ecological circumstances.
One wonders: will Dr. Meyer now reconsider his views?
A final thought
All I had to do was Google “evolution of Developmental Gene Regulatory Networks” and “developmental gene regulatory network in sea urchins” to uncover the articles I’ve cited. The reason why I did that was because I wanted to know what the latest scientific research indicated. So my question for today is: why has everyone over at the Discovery Institute heard of Professor Eric Davidson, while nobody appears to have heard of Dr. Phillip Davidson? Aren’t they even curious? You decide.
I’m not a biologist.
I did read (or at least skim through) that Luskin post. I was not impressed.
Yes, I’m sure it’s right that if you make a significant change in regulatory networks, it is likely to have a bad effect. But what about a small subtle change? Natural selection seems to do very well with the small changes and with finding ones that work well.
Good post Vincent.
Another factor to consider is that various forms of what biologists call entrenchment, has been observed to evolve in experiments. It has also been shown to have evolved using ancestral sequence reconstruction.
It’s basically a form of constructive neutral evolution. A novel interaction emerges between the proteins A and B (for example), which is initially entirely neutral. Then in protein A a function is lost, but the neutral interaction with B having previously evolved turns out to compensate for the loss of function in A. The initially entirely dispensable interaction (which could be considered a plastic trait) is now suddenly necessary and can no longer be lost. It has become entrenched.
The Thornton lab showed a great example of this with evolution of this sort of increased (and irreducible) complexity in the V-type ATP-synthetases all the way back in 2012:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979732/
Finnigan GC, Hanson-Smith V, Stevens TH, Thornton JW. Evolution of increased complexity in a molecular machine. Nature. 2012;481(7381):360-364. Published 2012 Jan 9. doi:10.1038/nature10724
Similar principles apply to gene regulatory networks. The entrenchment builds up over time as novel interactions and components emerge in the network, which makes subsequent changes more difficult as the different components of the system has become increasingly dependent on each other.
In a later study by the Thornton lab again, they showed how this entrenchment (this time as interactions between mutations in a single protein) built up over hundreds of millions of years so that, eventually, mutations in the ancestral protein sequence (experimentally confirmed to have been functional at some point in the past) eventually became deleterious in the modern genetic background:
https://www.pnas.org/doi/abs/10.1073/pnas.1718133115
Starr TN, Flynn JM, Mishra P, Bolon DNA, Thornton JW. Pervasive contingency and entrenchment in a billion years of Hsp90 evolution. Proc Natl Acad Sci U S A. 2018;115(17):4453-4458. doi:10.1073/pnas.1718133115
My bold:
There’s nothing “ad hoc” about the idea that novel interactions or adaptations (be they interactions between components in a gene-regulatory network, different protein components in a molecular machine, or individual mutations in a protein) become entrenched and indispensable over time.
As usual the Dishonesty Institute is engaging in selective literature references.
Hi Rumraket,
Thank you very much for the insightful points you’ve raised. I’ll be mentioning some of them in my forthcoming post. I especially liked this quote:
“There’s nothing “ad hoc” about the idea that novel interactions or adaptations (be they interactions between components in a gene-regulatory network, different protein components in a molecular machine, or individual mutations in a protein) become entrenched and indispensable over time.”