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Evo-Devo, promising more than is delivered?


Evolution of anatomy and gene control  Evo-devo meets systems biology. Georgy Koentges Nature Vol 451|7 February 2008  (excerpts only)

Since Darwin we know that we must explain organisms not only in mechanistic terms (of mutation, selection and adaptation on the population level) but also in historical terms, as ‘descent with modification’, evolution in phylogeny. All heritable morphological changes derive from developmental changes in molecular control hierarchies and networks.

Genetic control networks must have changed to create phenotypic diversity. Historians of life are interested in the specific succession of changes over evolutionary time.

It is difficult to conceptualize how single-molecule dynamics on two strings of DNA can cause major structural changes.

Molecular decisions made in mother cells of particular lineages affect three key phenomena: patterning, differentiation and growth.

Our intuitive preconceptions about can mislead us. We do not know in advance which anatomical characters will reveal the most about the underlying cell lineages.

The central players of evolutionary change are likely to be elements of the gene-regulatory machinery, transcription factors and their cognate genomic binding regions,
which are clustered in ‘cis-regulatory’ modules (CRMs) and promoters. Ultimately, major morphological changes can be viewed as epiphenomena of dynamic changes acting on regulatory gene nodes in key morphogenetic circuits.

Current estimates for CRM numbers in vertebrates are in the few thousands. CRMs are likely to act as logic functions, coincidence detectors, filters, gradient sensors and resistors, all of which ultimately influence the kinetics of activators, repressors, SRB/mediator complexes and Pol II-HECs, grouped in ‘factories’.

Talk about ‘co-option’ or ‘homology of regulatory cassettes’ is premature. Expectations about ‘master regulators’ may have to be reassessed. In vertebrates the expression domains of most patterning ‘master regulators’ have not changed significantly since agnathan times, despite obvious signs of morphological evolution.

There might be some initial disappointment that nature neither constructed its regulatory circuits with an engineer’s intelligence nor used Occam’s razor, whereas we must use both to describe it.

The links between evolution and systems biology are tenuous at the moment because of limitations in what we can measure.

We can now see more than Darwin could ever have imagined.

Bob O'H
The problem is finding an approach to the problem that has a reasonable chance of success.
Again this was discussed on Telic Thoughts. It seems that you need a large area (island?) that is isolated from all entry and escape of mice. (A leak here or there won't kill the data. Mice are hard to isolate.) Then, rather than using lab mice (it is suspected that they suffer from selective breeding) begin with wild mice. Knock out the conserved genes that you wish to test in 1/2 of the mice. Ideally, put in a genetic marker into all of the mice, a kind of barcode to confirm that all mice are part of the test rather than coming in from the outside. Run the experiment with around 1000 total mice 500 mutants, 500 controlls. Run the test for 5 years, doing regular statistical checks to see if the unmodified mice are dominating or not. If the modified mice continue to thrive in such an environment, then the modification can be reasonably labeled "unharmful". If the deletion of highly conserved genes proves unharmful in a major study like this, then the theory the the genes are conserved by natural selection becomes highly suspect. The science needs to be done. bFast
It seems as if knocking out the conserved sequences, raising the GM progeny, and comparing them with their unmodified cousins is the way to go.
Yep. But what environment are you going to grow them in? Bob Bob O'H
Bob It seems as if knocking out the conserved sequences, raising the GM progeny, and comparing them with their unmodified cousins is the way to go. Just because that's already been done with GM mice where a thousand highly conserved sequences were deleted and they couldn't find any differences doesn't mean there are no differences. Maybe they just didn't look hard enough. Lack of evidence is not proof of lack. Just like lack of direct evidence of non-human intelligent agency doesn't mean that there are no other intelligent agencies and therefore we must hold open the possibility that we just haven't looked hard enough. I'm sure you'll agree as I'm confident you're honest enough not to impose a double standard when it comes to lack of evidence, right? DaveScot
As such, if the scientific community is honest, it will output the bucks to do the heavy research to prove these conserved genes to be valuable.
I suspect they are doing. The selling point on the grant application is a no-brainer. The problem is finding an approach to the problem that has a reasonable chance of success. I can't see one, but I don't work in that area, so this is probably just my ignorance. Bob Bob O'H
bFast it will output the bucks to do the heavy research to prove these conserved genes to be valuable. Silly boy. If DNA is conserved it has function. If DNA has function it is conserved. I believe Judge Jones in Dover proved this to be true science and ordered, through judicial fiat, that questioning it violates the first amendment of the United States constitution. Don't make me turn you in to the authorities. Testing something that is known to be true is a waste of time. This stuff is as well tested as the law of gravity. No one needs to wonder if an apple is going to fall down from a tree or up into the sky. Similarly no one need wonder if conserved DNA has a function. It just does. DaveScot
Bob O'H, this is not the only report I have seen of highly and ultra-conserved genes showing no evidence of offering value to an organism. I had a major discussion on the topic about six months ago on Telic Thoughts. The argument always seems to come around to "its value might not show up in the sterile laboratory environment". This is a nice thing to say, but neo-Darwinism would be crushed if portions of DNA is highly conserved but not useful. As such, if the scientific community is honest, it will output the bucks to do the heavy research to prove these conserved genes to be valuable. Further, I suggest that if these genes are unneccesary in some environments, we should see that some organisms drop genes that are highly and ultra-maintained in their cousins and ancestors. I have not seen reports of this being the case. bFast
bFast - had idnet.com.au pasted more of the article, you would have seen the explanation is in measurable function. The paper points out that the function of CRMs is only investigated in short snapshots, but they may be acting outside of these, or under different environmental conditions, that do not occur in the lab. Bob Bob O'H
I see the phenomenon of highly conserved and ultra-conserved DNA which provides no measurable function to the organism to be a huge challenge to Neo-Darwinism, and, in fact, a major boost to the front-loading hypothesis. It implies, after all, that there is a separate conserving mechanism beyond natural selection. bFast
bFast, you're right. I didn't go to the trouble of looking up the references. One (Nachman and Crowell) estimate 1.7% is conserved "coding regions", mostly genes. This just makes the problem worse of explaining development from known conserved nuclear DNA. magnan
Magnan, my understanding is that about 1.5% of human DNA codes to protein. About 5% demonstrates conservation between man and mouse, and is therefore seen as "likely functional". The remaining 95% is seen as likely "junk". bFast
Fascinating. I found a concise description of CRMs: "Transcription regulatory regions in higher eukaryotes are often represented by cis-regulatory modules (CRM) and are responsible for the formation of specific spatial and temporal gene expression patterns. These extended, ~1 KB, regions are found far from coding sequences and cannot be extracted from genome on the basis of their relative position to the coding regions." A few questions come to mind. Are CRMs classified as non-coding "genes"? What other extra-nuclear DNA complexes than CRMs have been found to regulate gene expression? Basic informational quantity arguments would imply that most of the genome must be required to contain sufficient data to actually build a complex metazoan, like a mammal. I seem to recall that only 5-10% of the genome is coding genes, so this would imply that most of the remaining must be CRMs and other regulator complexes, and that accordingly these would have to be conserved. But neither of these expectations seem to be the case. (?) Does the above imply that much of the developmental information must be in the extranuclear cytoplasm, and replicate directly in cell division? magnan
Thanks Bob O'H idnet.com.au
From an ID perspective, I find the the following to be the most intriguing:
Recent studies on vertebrates suggest that only a fraction of ‘ultra-conserved’ CRMs are active and absolutely required for the animal to survive.
How on earth, within a neo-Darwinian context, is DNA "ultra-conserved" if it is not active or absolutely necessary? bFast
Very interesting fantasy article. It is funny how someone seems to start wondering how things work, and admitting that we practically don't understand anyting of how they work. And yet, everybody seems earnest to apply all kinds of fantastic evolutionary reasonings to such a void of knowledge! I have always stated that the principle of evo devo is absolutely correct. There is a deep apparent affinity between the mystery of phylogenesis and the mystery of ontogenesis, not in the sense that one is similar to the other, but in the sense that both are completely beyond our present understanding, that both are obviously designed, and that understanding one will certainly help understand the other, and vice versa. The only problem is that neither phylogenesis nor ontogenesis will ever be explained by darwinian models, or more generally by any purely reductionist model. A major shift of paradigm will be necessary, and it will certainly include the concepts of design and purpose. In the meantime, just for fun, one could try to count the number of words like "might" and "premature" and "tenuous" and "reassessed" and similar in the above article,and just ask oneself, how much new information was added to the article by its designer? gpuccio

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