Mike the Mad Biologist

An Evo-Devo Kerfuffle

In the May edition of Evolution, Hopi Hoekstra and Jerry Coyne have an interesting commentary, “The Locus of Evolution: Evo Devo and the Genetics of Adaptation.” They raise two points about “evo devo” (the fusion of developmental and evolutionary biology) that have always bothered me. From the abstract (boldface mine):

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.

Unfortunately, I can’t link to the article (otherwise I would shameless reproduce more of their arguments), but I’m inclined to agree with Hoekstra and Coyne. Ultimately, my ‘personal experience’–the systems I work in and know the most about–always led me to disagree with the breathless pronouncements that evolution happens in really different ways. So I’m glad to see two biologists with far better evo devo chops than me raise these objections.

(an aside: Most of my ‘personal experience’ has to do with microbial gene function. Nonetheless, anyone who argues that bacteria are ‘simple’ or don’t have complex networks of protein interactions is exposing their own ignorance. The complexity of moving an iron moiety into a bacterial cell would make an embryologist cringe.)

So onto the meat of the argument.

The primary claim is that adaptive mutations are more likely to happen in the regions ‘outside’ of the DNA that actually encodes the protein of interest: the former are the “cis-regulatory” regions, and the latter are the “structural regions.” There are two arguments used to support this claim. The first is theoretical. Changes in proteins (the structural regions) are far more likely to be deleterious because a change in a structural region alters every (or most) interaction that protein will have. Changes in the cis-regulatory region affect only the production of that individual protein. Thus, cis-regulatory changes are more likely because they are less likely to result in other maladaptive protein interactions (this is also know as negative pleiotropy).

There are two problems with the theoretical argument. First, many proteins are ‘modular’–changes in the structure of one part of the protein that has a particular function do not affect other functions of the protein. This pattern is particularly pronounced in those proteins that interact with other proteins (e.g., the BtuB receptor protein). In fact, to the extent there is functional overlap, it often occurs So I’m not necessarily buying the natural history story.

The second issue is that regulatory changes in the expression of a given protein can alter the cascade of events that follow on from that protein’s function. While this is most obvious in metabolism, where the result of an enzymatic reaction can directly affect the induction of the next step of the pathway, it would appear to apply more generally in any spatiotemporally patterned biological process–including development.

The evidence of the importance of cis-regulatory regions also appears to less robust than I thought. Hoekstra and Coyne write:

The data, though they may suffer from ascertainment bias, also show no strong evidence for important cis-regulatory change in evolution. In contrast to the many known adaptive changes in protein structure (some of which may have opened new ways of life for animals), there are only a handful of examples that are probable cases of adaptive cis-regulatory evolution. And, in contrast to the evidence for structural change, all three of the most widely cited cases have not yet produced definitive evidence that cis-regulation is involved. Moreover, these three cases focus on losses of traits rather than the origin of new traits, and in only one of the three (loss of pelvic structures in stickleback fish) is there a clear adaptive explanation for the trait loss. Obviously, we still cannot make sound generalizations about the molecular basis of adaptation. What we can say is that adaptations of both form and physiology are likely to involve a mixture of structural and cis-regulatory changes, and that structural changes are unlikely to be negligible.

The data (table 1 if you have the paper) they present support their statement. To make it clear, I’m not denying the importance of regulation, but to argue that it is the dominant form of adaptation seems premature.

an aside: I think microbiology is just starting to experimentally assess the role of gene expression (outside of several model systems such as the lac operon), and we probably are underestimating its importance. Nonetheless, it is interesting to note that some of the best characterized adaptive phenotypes that occur in natural habitats (e.g., antibiotic resistance, tissue adhesion) typically involve structural changes far more than changes in gene regulation. Just throwing more fuel on the fire (and DS if you don’t comment, I’ll be disappointed…).

Creationist troll-be-gone: If you assume that this post indicates that ‘evolution is a theory in crisis’ or some other silliness, pour yourself a tall glass of Shut the Fuck Up. You’ll note that one of the two counter-arguments that Hoekstra and Coyne present is data-driven. Data, not ‘faith.’

Comments

  1. #1 Chris Harrison
    June 21, 2007

    Hi Mike. Larry posted about Hoekstra and Coyne’s paper here:
    http://sandwalk.blogspot.com/2007/06/skepticism-about-evo-devo.html

    I just wanted to drop the same comments here that I left there. Coyne and Hoekstra seem to overstate the views of the evo-devo guys and I think their overall conclusion, that saying cis-regulatory mutations are a major players in adaptation is “premature”, is wrong.

    Anyway, 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.” Wray also puts together a table of known traits that result from variations in cis-regulatory regions.

    Here’s the full text of Wray’s paper:
    http://www.biology.duke.edu/wraylab/papers/NRG0307.pdf

  2. #2 şişme bebek
    June 11, 2009

    The data (table 1 if you have the paper) they present support their statement. To make it clear, I’m not denying the importance of regulation, but to argue that it is the dominant form of adaptation seems premature

  3. #3 sex shop
    August 28, 2009

    Does every middle-aged guy who’s watched too much Jon Stewart have to now randomly inject ‘…wait for it…’ in between parts of a sentence? It’s not funny. It’s just annoying.

The site is undergoing maintenance presently. Commenting has been disabled. Please check back later!