Pharyngula

Evo-devo wars

Fellow scienceblogger Evolgen has seen the light—evo-devo is wonderful. He’s attending a meeting and listening to some of the bigwigs in the field talk about their work, in particular some research on the evolution of gene regulation. While noting that this is clearly important stuff, he also mentions some of the bickering going on about the relative importance of changes in cis regulatory elements (CREs) vs. trans acting elements, transcription factors. I’ve got a longer write-up of the subject, but if you don’t want to read all of that, the issue is about where the cool stuff in the evolution of morphology is going on. Transcription factors are gene products that bind to regulatory regions of other genes, and change their pattern of expression. The things they bind to are the CREs, which are non-coding regions of DNA associated with particular genes.

This cartoon might help you see the difference.

One key difference is that a change in a transcription factor has the potential to affect many genes all at once; it can represent a larger evolutionary “jump”, and most would argue that it has a lower chance of being viable. A change to a CRE, on the other hand, is more discrete and changes where and when a single gene might be active. That would seem to represent a more viable kind of change, and is more incremental. There is an active debate about the dominant mode of regulatory change going on, as evolgen notes:

Sean Carroll likes to point out how important CREs are in the evolution of form. Bustamante joked (with Carroll in the room) that his data paint a very different picture, with transcription factors playing an important role. Why do they take such a polarizing stance? Well, controversy fuels excitement. If we all just acknowledged that cis and trans changes are important, we could move on toward understanding how these two regulatory mechanisms work together to contribute to evolutionary change. Carroll’s story is incomplete without understanding why the wing spot phenotype is sexually dimorphic — probably due to some trans regulation. Furthermore, Bustamante and Andolfatto have shown that both transcription factors and CREs contain signatures of positive selection. Wittkopp was the only one to simultaneously examine cis and trans factors, finding evidence that both are evolutionarily important. Let’s end the stupid bickering– it’s not doing anyone any good.

Wait, no, I disagree. All sides in this argument know that the others are at least partially right on the matter: I’m sure Carroll and Bustamante look at each other’s work and say “Cool.” However, I love seeing this kind of bickering in science. The brains on each side are buzzing and thinking of new ways to evaluate their preferred hypothesis and put those other guys in their place. That dynamic of conflict is exactly what drives a lot of focused, productive research, and the end result will be a lot of data. I agree it’s got to be both, but what the science will do is give us specific instances where CRE evolution is important, and another set where trans factor evolution is important. We all win!

In fact, I wonder if a reason the two PIs play up the debate is to motivate their students, who are going to do the actual work.

Comments

  1. #1 RPM
    May 31, 2006

    Carroll’s work is excellent, but it seems as if he is working with some a priori assumptions regarding the importance of cis changes. His work does support his hypothesis, but he doesn’t really investigate any of the trans factors that may be invovled. He hinted that this may become necessary if he wishes to examine species outside the melanogaster group using transgenic D. melanogaster.

    Carlos Bustamante, on the other hand, isn’t even looking at non-coding DNA (his data set is limited to coding regions). This disconnect is not very encouraging

    The most interesting study, imo, was Tricia Wittkopp’s because she simultaneously looked at cis and trans changes. That project was not easy to digest (I remember her explaining the logic to a bunch of confused population geneticists at the fly meetings a couple of years ago), but it was devoid of the bias with which Carroll seems to approach evo-devo.

    Also, studies like Andolfatto’s, which compare signatures of selection in non-coding and coding DNA, would complement Tricia’s work nicely.

  2. #2 Bronze Dog
    May 31, 2006

    That dynamic of conflict is exactly what drives a lot of focused, productive research, and the end result will be a lot of data.

    Unlike woodom, where they’re all supportive of each other, even if they have opposite positions of what color aura is best for your colon.

  3. #3 bsa
    June 1, 2006

    I can’t comment on the specifics here (no knowledge base) but I wonder if this isn’t another example of why most of the public distrusts science and scientists. These guys are smart and like to argue; most everyone else seems to avoid confrontation (again, especially with smart people who will kick your ass publically). We fear being “wrong” and prefer our “gut instincts” (ala Colbert); who can argue with my true feelings? Is there anyway we can communicate that clarity of thought is not dangerous?

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