first a description of CREs and their role from the paper, and then the abstract below:
"Most loci encoding pattern-regulating proteins were found to include multiple individual cis-regulatory elements (CREs), with each CRE typically comprising binding sites for multiple distinct transcription factors and controlling gene expression within a discrete spatial domain in a developing animal. The realization that the total expression pattern of a gene was the sum of many parts, each directed by distinct CREs, marked a profound change in concepts of gene regulation. The modular arrangement of CREs also had clear implications for evolutionary genetics, because it suggested a mechanism for how selective changes in gene expression and morphology could evolve in one part of the body, independent of other parts. The conservation of the biochemical activity of regulatory proteins, the divergence of their expression patterns across taxa, and the modular organization of CREs provided the basis for the general proposal that gene expression evolution, and therefore morphological evolution, would occur primarily through changes in cis-regulatory sequences controlling gene transcription."
Emerging principles of regulatory evolution
Benjamin Prud'homme, Nicolas Gompel, and Sean B. Carroll
PNAS | May 15, 2007 | vol. 104 | Suppl. 1 | 8605-8612
Understanding the genetic and molecular mechanisms governing the evolution of morphology is a major challenge in biology. Because most animals share a conserved repertoire of body-building and -patterning genes, morphological diversity appears to evolve primarily through changes in the deployment of these genes during development. The complex expression patterns of developmentally regulated genes are typically controlled by numerous independent cis-regulatory elements (CREs). It has been proposed that morphological evolution relies predominantly on changes in the architecture of gene regulatory networks and in particular on functional changes within CREs. Here, we discuss recent experimental studies that support this hypothesis and reveal some unanticipated features of how regulatory evolution occurs. From this growing body of evidence, we identify three key operating principles underlying regulatory evolution, that is, how regulatory evolution: (i) uses available genetic components in the form of preexisting and active transcription factors and CREs to generate novelty; (ii) minimizes the penalty to overall fitness by introducing discrete changes in gene expression; and (iii) allows interactions to arise among any transcription factor and downstream CRE. These principles endow regulatory evolution with a vast creative potential that accounts for both relatively modest morphological differences among closely related species and more profound anatomical divergences among groups at higher taxonomical levels.