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Evolvability

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Marc Kirschner and John Gerhart Evolvability. Proc. Natl. Acad. Sci. USA 95(15), 1998.  PNAS page pdf

This hugely influential paper attempts to uncover the high-level features of complex biological architectures that facilitate their phenotypical variation. The authors analyse several examples of  highly conserved mechanisms they call “core processes” and argue that

the conservation of these core processes for the past 530 million years is related less to the processes’ own constraint, embedment and optimization than to the deconstraint they provide for phenotypic variation of other processes, on the basis of which they are continually coselected.

Now, the obvious interpretation of evolutionary conservation is that the conserved process plays an important role in a crucial function of the organism and/or confers a significant fitness advantage. Kirschner’s and Gerhart’s suggestion that this advantage is in fact evolvability itself goes (in general) dangerously close to invoking group selection, and they acknowledge as much. I do not feel (yet) competent to comment on this, so I will review instead the excellent observations that the authors make about the high-level organisational priciples that contribute to evolvability.

Versatile proteins are pretty much what it says on the tin: proteins that are not very specific, but admit a range of targets. The example given in the paper is that of calmodulin, a prominent player in various calcium-based signalling pathways. Calmodulin usually inhibits the function of the protein it binds to, but because the range of targets it recognises is so broad, the inhibited agent can be an inhibitor itself, or maybe an activator, etc. As a result, calmodulin has great value as an universal negation gate in many different regulatory contexts. Dually, because of the low general specificity, a random regulator protein is presumably just a few mutations away from responding to calmodulin and the emergence of a new regulatory connection. Thus the versatility of calmodulin faciliates phenotypic variation of a regulatory network.

Weak linkage means that “the activity of a process depends minimally on other components or processes”. This is a fuzzy concept to me. Judging by the examples given in the paper, this is yet another face of the flexibility and versatility covered in the previous paragraph and it is unclear to me why the two should be treated separately, other than perhaps the fact that weak linkage refers not as much to the individual components of the system as to the way they are put together. The authors discuss weak linkage in eukariotic transcription and this is perhaps what the paper is known for the most: bringing to the fore the evolution of regulation (as opposed to the evolution of structural genes).

Exploratory processes perform their function relying as little as possible on the particulars of their client/target processes. One example given in the paper is the microtubule cytoskeleton helping to separate chromosomes before cell differentiation: the tubules grow in random directions, but stablise only when they find the chromosome. In this way, the skeleton is built correctly regardless of the initial positions of the chromosomes, cell size and shape, etc. These parameters are thus free to change, and this is why the exploratory formation of the cytoskeleton facilitates phenotypic variation. Another example is the immune system, which randomly generates antibodies until the right one is recognised. The authors also refer to this design principle as “epigenetic variation and selection”.

Compartmentation is just an ugly word for modularity, only that the modules/compartments may be genomic (different genes for different things), temporal (i.e. processes happen in stages), spatial, or even target-spatial i.e. the same process is independently deployed and regulated in different regions of cell/tissue (example: drosophila bristle development). This kind of architecture facilitates phenotypic variation because brakedown of one module does not necessarily entail the brakedown of the whole system. A computer scientist would probably advocate the value of interfacing and hiding at this point.

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April 3, 2010 at 19:20

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