Monday, June 18, 2007

Skepticism About Evo-Devo

 
The May issue of Evolution contains an article by Hoekstra and Coyne on Evolutionary-Developmental Biology or Evo-Devo. There are many evolutionary biologists who have serious doubts about the claims of evo-devo but these doubts don't often make it into the scientific literature because it's very hard to publish critiques. The Hoekstra and Coyne (2007) article is a welcome contribution to the debate.

Here's the abstract,
An important tenet of evolutionary developmental biology (“evo devo”) is that adaptive mutations affecting morphology are more likely to occur in the cis-regulatory regions than in the protein-coding regions of genes. This argument rests on two claims: (1) the modular nature of cis-regulatory elements largely frees them from deleterious pleiotropic effects, and (2) a growing body of empirical evidence appears to support the predominant role of gene regulatory change in adaptation, especially morphological adaptation. Here we discuss and critique these assertions. We first show that there is no theoretical or empirical basis for the evo devo contention that adaptations involving morphology evolve by genetic mechanisms different from those involving physiology and other traits. In addition, some forms of protein evolution can avoid the negative consequences of pleiotropy, most notably via gene duplication. In light of evo devo claims, we then examine the substantial data on the genetic basis of adaptation from both genome-wide surveys and single-locus studies. Genomic studies lend little support to the cis-regulatory theory: many of these have detected adaptation in protein-coding regions, including transcription factors, whereas few have examined regulatory regions. Turning to single-locus studies, we note that the most widely cited examples of adaptive cis-regulatory mutations focus on trait loss rather than gain, and none have yet pinpointed an evolved regulatory site. In contrast, there are many studies that have both identified structural mutations and functionally verified their contribution to adaptation and speciation. Neither the theoretical arguments nor the data from nature, then, support the claim for a predominance of cis-regulatory mutations in evolution. Although this claim may be true, it is at best premature. Adaptation and speciation probably proceed through a combination of cis-regulatory and structural mutations, with a substantial contribution of the latter.

Hoekstra, Hopi, E. and Coyne, Jerry, A. (2007) THE LOCUS OF EVOLUTION: EVO DEVO AND THE GENETICS OF ADAPTATION. Evolution 65:995–1016.

13 comments :

  1. Do Evo-Devo types like Sean B. Carroll actually argue that "that adaptive mutations affecting morphology are more likely to occur in the cis-regulatory regions than in the protein-coding regions of genes?" That's not quite how I read Endless Forms Most Beautiful - although I could have missed that passage, I read Carroll as arguing just that the structural body plan of metazoan life was better explained by cis-elements. Also, in Making of the Fittest, Carroll clearly makes the case for structural mutations in non-developmental changes.

    I'm sure one could dig up an evo-devo paper that overstates the case for cis-elements (I don't follow such journals closely), but Hoekstra and Coyne seem to be overstating the "tenets" of evo-devo, in some sort of straw-man, to make their paper more interesting.

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  2. Well it is also silly to think that "evo-devo" can be boiled down to the affirmation that regulatory mutations are most important for evolution. I work within the field of evo-devo but I am not enthusiastic about that notion and several other notions upheld by evo devo hotshots like carroll and davidson. To me an important part of evo-devo is the discussion of homologies and the still quite underappreciated role of constraints and hopeful monsters in evolution. In this we can already say that natural and experimetal evolution confirs that adpatation involve a few genes of great effect, not so the accumulation of "micromutations" so dear to researchers that may wish to publish in a neodarwinian journal like "evolution" (NOT the most varied representative of the actual richness of evolutionary research, to put it mildly)

    -Alipio

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  3. Having no experience of the field, I have no opinion of evo-devo or its most popular claims.

    so dear to researchers that may wish to publish in a neodarwinian journal like "evolution" (NOT the most varied representative of the actual richness of evolutionary research, to put it mildly)

    If we're going to get a bit of anger at Evolution going, I'll jump on that bandwagon and mention the not-quite-joking assertion that frequently comes up around here that the journal should be renamed "Microevolution". Yay, you discovered yet another single locus that has a tiny effect in a single population of a single species in some vaguely-related-to-selection way. [/sarcasm]

    Seriously, though, I agree with Dan, above, that that abstract looks a bit overstated. I don't think I'd go so far as to use the term "straw-man", but perhaps Hoekstra and Coyne focus too much on this one hypothesis coming out of evo-devo research. A welcome addition to the debate, at least, as you said.

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  4. I read Hoekstra and Coyne's paper about a week ago, and mentioned it in a post here:

    http://interrogatingnature.blogspot.com/2007/06/how-important-are-cis-regulatory.html

    There is a lot of rhetoric in Coyne's paper, and it does come off a bit pretentious and overstated, as Dan said.
    As I mentioned in my post, right after Coyne and Hoekstra's critical paper was published, Gregory A. Wray submitted "The evolutionary significance of cis-regulatory mutations", which argues in line with Carroll and the developmental biologists that the importance of CREs in evolution is "empirically well supported: numerous studies have identified cis-regulatory mutations with functionally significant consequences for morphology, physiology and behaviour."

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  5. Eh. This sounds exactly like Coyne's review in Nature of Carroll's book. I don't quite get it. His argument seems to consist of overstating evo-devo, and then shooting down arguments Carroll doesn't make. For instance, he cites gene duplication, gene conversion, exon shuffling, etc. as examples of evolutionary changes that don't involve changes in gene regulation, as if evo-devo proponents had been arguing that those don't occur. He also argues that evo-devo is speculative because...

    We now know that humans and chimps have different amino-acid sequences in at least 55% of their proteins, a figure that rises to 95% for humans and mice. Thus we can't exclude protein-sequence evolution as an important reason why we lack whiskers and tails.

    ...which makes no sense at all. Evo-devo does not claim protein sequence evolution does not occur, so that's pretty damned silly right there. But of course we know that changes in pattern also have to involve changes in regulation. Hairs and a post-anal tail are not innovations in mice. What mice have is a resculpting of the organization and expression of genes involved in making those structures. We know that there had to be protein evolution, but we also know that there had to be evolution of regulation.

    The question Coyne asks is one of relative importance. It's the wrong question: they're both very important. I'll take a quick look through Endless Forms... later and see if there's anything there that implies that protein evolution is trivial, but I certainly don't remember anything like that from my prior reading, and Coyne's Nature review didn't bring up any damning quotes either, so I rather suspect that Coyne is flailing strenuously against a straw man here.

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  6. PZ, either the evo-devo proponents are making a claim about something novel and important in the evolution of animals, in which case they're wrong, or they're simply pointing out things that we already knew, in which case they're not saying anything important.

    What do you think is the most important contribution of evo-devo to the study of evolution?

    Everyone who writes about evo-devo—and this includes Kirshner and Gerhardt—emphasizes change driven by regulatory sequences and regulatory proteins (especially HOX genes). They're all smart enough to mention other possibilities.

    Nobody thinks that evo-devo is advocating that all changes occur by mutating regulatory sequences. However, it's convenient to focus of this when criticizing evo-devo since it's the main claim to novelty in evolutionary theory.

    I see the debate as being similar to the adaptationist-pluralist debate. There's a lot of rhetoric on both sides but that doesn't mean that the issue is unimportant.

    The adaptationists are fond of claiming to be misrepresented and they can pick out passages where they freely admit to the important of random genetic drift. "See," they claim, "we're not as dogmatic as you claim." That's how they dismiss their opponents by invoking the "strawman" defense instead of actually coming to grips with the real issues.

    Are the evo-devo proponents going to take this approach as well?

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  7. Thanks to Chris Harrison for pointing out the Wray paper ( http://www.biology.duke.edu/wraylab/papers/NRG0307.pdf ). At least to my layperson's reading, it resists rhetoric in favor of a survey of recent research aimed at seeing whether regulatory changes have qualitatively different evolutionary effects than coding changes.

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  8. IMHO Larry overstates:

    PZ, either the evo-devo proponents are making a claim about something novel and important in the evolution of animals, in which case they're wrong, or they're simply pointing out things that we already knew, in which case they're not saying anything important.


    Evo-devo presents a major new understanding of animal evolution, correctly.
    No, you didn't already know it. Otherwise you could have published and had several Nobel prizes concerning conserved developmental pathways and the remarkable sensitivity of morphology to specific genes.

    Are evo-devo-ists likely to say, in so far as they bother with this sort of debate at all, that no, they're not denying other aspects of evolution, they are simply studying what they are studying like anyone else? Would that be surprising?

    - Pete Dunkelberg

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  9. Pete Dunkelberg says,

    Evo-devo presents a major new understanding of animal evolution, correctly.

    No, you didn't already know it. Otherwise you could have published and had several Nobel prizes concerning conserved developmental pathways and the remarkable sensitivity of morphology to specific genes.


    There's a big difference between finding out specific information about development on the one hand, and discovering fundamental new concepts, on the other.

    Of course it was interesting to discover the molecular details of homeotic genes and of course the discovery of how regulatory genes affected development in Drosophila was deserving of a Nobel Prize.

    What I was referring to was the basic concept. The fact that genes are regulated was already known and the fact that differential regulation could produce different phenotypes was not something that animal developmental biologists discovered.

    Everyone that I hung out with in the late 60's believed that the basic concepts of gene regulation and development would apply to animals in the same way that they applied to bacteriophage lambda. As it turns out, they were correct.

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  10. There's a big difference between finding out specific information about development on the one hand, and discovering fundamental new concepts, on the other.


    This seems to be a discussion if an area is a specialty (own focus, funding and methods) or a field on its own right (own theory).

    For a layman it is always confusing with the background and reasons for the debate, so I'm glad the discussion was so poignantly framed. [The proper use of a concept of framing, I think. :-)]

    Alas, the width and length of it will never be transparent, though Larry gives helpful hints here too. Nice.

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  11. "Everyone that I hung out with in the late 60's believed that the basic concepts of gene regulation and development would apply to animals in the same way that they applied to bacteriophage lambda"

    So? That does not mean that development is not important for understanding evolution. We can't just collapse the organismal-development level existing between gene an population, like some would have it.

    And then of course, gene regulation and development is a quite basic thing. To discover that these basic cellular processses are universal I agree is no big surprise. That's why it is silly to think THAT is the great discovery of evo-devo. No; the great discoveries of evo-devo deal with morphological traits of the body plans of metacelullar organisms, such as antero-posterior and dorso-ventral aptterning, that were previously thought to be the result of convergent adaptation and were not suspected to be patterned by the same genes and similar rules of development. To discover that similar general molecular mechanisms underly regulation of gene expression in mouse and fly is not surprising. What is surprising is to discover that the side of the body on which the nervous system develops is psecified by homologous genes is, indeed, revolutionary, as a previously unexsiting image of a common ancestor with a polarized distribution of its nervous system emerges. A completely different evolutionary history form the previous one.

    -Alipio

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  12. What is surprising is to discover that the side of the body on which the nervous system develops is psecified by homologous genes is, indeed, revolutionary, as a previously unexsiting image of a common ancestor with a polarized distribution of its nervous system emerges. A completely different evolutionary history form the previous one.

    I'm afraid this is mostly bogus, considering that Étienne Geoffroy Saint-Hilaire proposed this exact idea back in the early 1800s.

    Less spectacularly, if evolutionists think that shared traits derive from a common ancestor, which they typically do, then it is not all that surprising that all animals have homologous features in their body plans, considering that groups like "coelomates" and "bilaterians" have been standard for 100+ years AFAIK.

    Lastly...

    The thing everyone is forgetting in this thread is that the whole point of evo-devo in the first place is to bring developmental biology into the Neodarwinian Synthesis, or neo-Neodarwinian synthesis or whatever you want to call it. Population genetics brought together genetics and natural selection, and this eventually incorporated neutral drift, molecular evolution etc. Evo-devo ties classical developmental biology to genes and gene regulation and thus ties it in to population genetics and molecular evolution which was impossible before.

    Not that I don't like a good little old-fashioned feud between population geneticists and developmental biologists, but really it's all a little tiresome and 20th-century at this point. Everyone who is paying attention knows that evolution operates across several different hierarchies at once: organizational, from molecules to cells to organisms to biomes; temporal, from molecular interactions to geological; lineage/spatial, from individuals to populations to species to lineages; etc. Hype and counter-hype is not very productive; what would be better is to see where & how everything fits together in the different scales and hierarchies.

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  13. Only an unsincere person would ommit the well known fact that the ideas of geoffroy were until not too long ago ridiculed as the result of the metaphysics of the german naturphilosophen. Remember the adaptationist argument about the mouth? In a neodarwinian world, such adaptationist arguments went far... and by the way, not until the last year or so has the dorso-ventral inversion been completly accepted. Yes, there was still resistance, see the papers by Gerhart about a radial ancestor and independent condensation on different sides of the body, etc.
    Some competely underinfomed person could also fail to recognize that any previously acknowledged bilaterian was admited to be of only flatworm complexity: That is, no coelomic cavities, no heart, no appendages, nor any of other complexities brought up by that evo-devo evidence that fails to suprise some cynics who, of course, already knew all that. Pffff yeah right. So far for intellectual honesty.

    It would be wrong to think that population genetics does not pretend a hegemony through a conceptual reduction of actual complexity to otis own simple terms. It cannot reach too far on other approaches and sources of information and still claim to be "central" to the understanding of evolution. It is limited by its simplicity; to approach real world conditions, the models change dramatically, become quite complex, and the role of selection is more limited. And of course, while these models help answer theoretical questions, they are not "the way evolution works".

    I don't think we must assume that different approaches and sources of information should be amalgamated into some "synthesis" other than the common notion of a scientific "body of knowledge" used in any science.
    There should be no idea of a "neodarwinian synthesis" for anyone to "cherish".

    The hegemonical and reductionist approach at the heart of population genetics impedes it from being truly capable of integration.

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