Alternative routes and mutational robustness in complex regulatory networks


Although some have called systems biology a ‘friend of Intelligent Design’, reality is that systems biology is all but a friend of what is best known as ‘ignorance’.

In a recent article in BioSystems 88 (2007) 163–172, titled “Alternative routes and mutational robustness in complex regulatory networks”, Andreas Wagner and Jeremiah White describe how

Alternative pathways through a gene regulation network connect a regulatory molecule to its (indirect) regulatory target via different intermediate regulators. We here show for two large transcriptional regulation networks, and for 15 different signal transduction networks, that multiple alternative pathways between regulator and target pairs are the rule rather than the exception. We find that in the yeast transcriptional regulation network intermediate regulators that are part of many alternative pathways between a regulator and target pair evolve at faster rates. This variation is not solely explicable by higher expression levels of such regulators, nor is it solely explicable by their variable usage in different physiological or environmental conditions, as indicated by their variable expression. This suggests that such pathways can continue to function despite amino acid changes that may impair one intermediate regulator. Our results underscore the importance of systems biology approaches to understand functional and evolutionary constraints on genes and proteins.

So while ID proponents are arguing for an ‘edge’ to evolution, real science is uncovering a remarkable richness for evolution.

So let me ask the following question: Who has contributed to scientific knowledge here?

The question now becomes, how can such robustness evolve?

The answer, not surprisingly, is via Darwinian pathways…

The topology of cellular circuits (the who-interacts-with-whom) is key to understand their robustness to both mutations and noise. The reason is that many biochemical parameters driving circuit behavior vary extensively and are thus not fine-tuned. Existing work in this area asks to what extent the function of any one given circuit is robust. But is high robustness truly remarkable, or would it be expected for many circuits of similar topology? And how can high robustness come about through gradual Darwinian evolution that changes circuit topology gradually, one interaction at a time? We here ask these questions for a model of transcriptional regulation networks, in which we explore millions of different network topologies. Robustness to mutations and noise are correlated in these networks. They show a skewed distribution, with a very small number of networks being vastly more robust than the rest. All networks that attain a given gene expression state can be organized into a graph whose nodes are networks that differ in their topology. Remarkably, this graph is connected and can be easily traversed by gradual changes of network topologies. Thus, robustness is an evolvable property. This connectedness and evolvability of robust networks may be a general organizational principle of biological networks. In addition, it exists also for RNA and protein structures, and may thus be a general organizational principle of all biological systems.

Ciliberti, S, Martin, OC, Wagner, A. (2007) Robustness can evolve gradually in complex regulatory networks with varying topology. PLoS Computational Biology 3(2): e15.


Another interesting paper that should be noted was in last week’s Science Express: “Crystal Structure of an Ancient Protein: Evolution by Conformational Epistasis.” Sounds like nature found a way around evolution’s edge.

Great summary in last line of abstract: ““Permissive” mutations—substitutions of no immediate consequence, which stabilize specific elements of the protein and allow it to tolerate subsequent function-switching changes—played a major role in determining GR’s evolutionary trajectory.”

The relevance of this work is that while ID activists are desperately searching for edges, science is working on increasing our understanding of evolution. In doing so, science finds that the evidence strongly supports a Darwinian gradual pathway.

What does ID have to offer? A movie?

Syntax Error: not well-formed (invalid token) at line 5, column 12, byte 240 at /usr/local/lib/perl5/site_perl/5.12.3/mach/XML/ line 187

These findings, like so many findings by science, strongly contradict the assertions by Dembski and Behe that there is an edge to evolution. In fact, the more we learn about the pathways involved, the more we can marvel at the creative powers of evolutionary processes.

No wonder ID has to hide in the shadows of our ignorance.

ID advocates cannot demonstrate an “edge to evolution” despite their best attempts. They have however aptly demonstrated an edge to their couriosity, imagination and knowledge. Fortuntaely, reality is not limited by these constraints.

Behe has claimed, despite all evidence to the contrary, that there is no evidence for the evolution of complex biochemical pathways. If no creationist has yet done so, I am sure that in the future we will hear that there is no evidence for the evolution of complex genetic regulatory pathways either. This is a good example of the type of evidence that can be used to refute such claims. Hopefully studies such as this will help to create a new field for the study of the evolution of regulatory complexity.

As a non-scientist, interested mostly in the history of ToE, it looks to me like we’re on the edge of a quantum jump in understanding of evolution, thanks largely to the availability of whole genomes. Ernst Mayr’s idea that evolution was driven by mutations in genes sounds like something from the dark ages, now. (Meaning no offense to Dr. Mayr. I’m sure he’d be fascinated by the recent advances.) My guess is that problems in evolutionary theory are going to start falling like a house of cards. Is this going to be reported in the popular press, though, as ‘ToE more solid than ever,’ –or ‘New studies shed doubt on Neo-Darwinian ToE’? Is there a new SJG coming along to take the recent advances and put them in terms we common folk can easily digest?

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This page contains a single entry by PvM published on August 22, 2007 11:52 AM.

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