Emerging principles of regulatory evolution

Abstract

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.

Fig. 1.

Wing pigmentation pattern diversity across higher Diptera. This plate illustrates the diversity of wing pigmentation patterns in the Acalyptratae, a large group of higher Diptera (Cyclorrhapha), which contrasts with the remarkable conservation of shape, dimension ratios, and venation patterns of these wings after >70 million years of evolution.

Fig. 2.

Regulatory evolution and wing pigmentation pattern diversity. A suite of transcription factors control the development of the fly wing, each one being expressed in a particular pattern. Altogether, these expression patterns constitute a wing trans-regulatory landscape, conserved among Drosophila species (Top). The recruitment of a subset of the trans-regulatory landscape components by pigmentation genes results in the corresponding redeployment of these genes (Middle) and ultimately in a novel wing pigmentation pattern (Bottom). The recruitment of different combinations of trans-acting factors in different fly species yields distinct pigmentation patterns. In Middle, colored shapes represent binding sites for different trans-regulatory landscape components.

Fig. 3.

A glimpse of the actual wing trans-regulatory landscape. The expression of GFP reports the expression patterns of various wing transcription factors at the time pigmentation genes are being expressed.

Fig. 4.

Cis-regulatory evolution circumvents pleiotropic effects. The yellow locus contains a series of CREs controlling the spatiotemporal expression of the gene. Four of them are represented on these schematics, driving expression in the wing blade, wing spots, segmental abdominal stripes, and male posterior abdominal segments. Some species have lost the wing spots or male abdominal pigmentation (Middle and Bottom, respectively) through the inactivation of the corresponding CRE. The selective disruption of a CRE does not affect other aspects of the expression pattern or the gene activity.

Fig. 5.

Regulatory changes underlying male abdominal pigmentation pattern evolution. In the D. melanogaster species group, the male abdominal pigmentation pattern is variable (Right). In the ancestral situation, here illustrated with Drosophila willistoni, both sexes carry an identical segmental stripe pattern. D. melanogaster males have evolved fully pigmented posterior segments (A5 and A6). This pattern has been secondarily lost in Drosophila kikkawai. These transitions result in part from changes in the regulation of the pigmentation gene yellow (Center). The gain and the loss of binding sites for the Hox protein Abd-B, a transcription factor expressed in posterior segments in Drosophila (Left), was involved in the gain and loss of expression of Yellow in the posterior abdomen, respectively.

Fig. 6.

Body-plan evolution by compounding regulatory changes. Hindwing reduction in Diptera results from changes in the regulatory connections between the Hox protein Ubx (red) and downstream target genes (–5). In Diptera, a suite of wing-patterning genes have evolved Ubx-binding sites in their CREs and, as a result, are repressed during hindwing development. In contrast, in four-winged butterflies, Ubx regulates a distinct set of target genes in the hindwing.