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.