Trends in Genetics
OpinionPerspectives on Gene Regulatory Network Evolution
Section snippets
GRNs and Their Components
King and Wilson [1], in their seminal paper demonstrating human–chimpanzee proteome similarity, popularized the notion that regulatory changes play a major role in evolution. This idea, subsequently championed by influential evolutionary developmental biologists such as Sean Carroll and the late Eric Davidson 2, 3, has been strengthened by the recent availability of hundreds of fully sequenced animal genomes. The prevailing paradigm is that a relatively small set of common ‘toolkit’ genes shape
Modes of GRN Evolution
Studying GRN evolution at a detailed molecular level is more challenging than it might initially appear. To do so, we require well-defined GRNs (i.e., with both TFs and sufficiently characterized CRMs) in not just one species but rather in two or more related species (note that more than two species are necessary if the direction of evolutionary change is to be inferred). As there remain relatively few highly characterized GRNs even in a single species, this represents a significant obstacle.
Hidden Complexity in GRN Evolution
Many of the described instances of GRN evolution in place involve seemingly simple changes such as loss of the Pitx1 enhancer in sticklebacks [7] (leading to the absence of an important trans-acting regulator throughout the GRN) or modification of the bab enhancer for Drosophila dimorphic body pigmentation [10] (a cis-regulatory change affecting a downstream patterning event). Such a mechanism, GRN evolution by means of an individual cis-regulatory change, seems reasonable as the GRN is already
Putting the GRNs into DSD
Studies of evolutionary developmental biology have revealed cases in which, although a developmental pathway appears to have changed, there is no corresponding change in outcome: the phenotype is maintained despite apparent genetic rewiring. This phenomenon has been referred to in the literature as DSD or, less commonly, ‘phenogenetic drift’ 26, 27. Although the literature on DSD and GRN evolution have remained largely separate, it seems clear that DSD represents a form of GRN evolution, and I
Genomes and Regulatory Annotation
Given the importance of CRM-level data for the study of GRNs and GRN evolution, to what extent is such information available? The most detailed data are for D. melanogaster, for which the REDfly databasei has curated more than 22 000 empirically validated regulatory sequences, over 5800 of which are CRMs identified through in vivo reporter gene analysis and which therefore have associated spatial and temporal functional annotations [35]. Similarly, the Vista Enhancer Browserii [36] contains
CRM Discovery in Multiple Species
Fortunately, methods for CRM discovery, both empirical and computational, have improved dramatically in the past several years (reviewed in [43]), and examples of GRN evolution have now been observed in all of the common metazoan model species. Particularly strong examples are available from the echinoderms due to the extensive cis-regulatory analysis that has been performed on sea urchin development [44], but several well-described vertebrate instances exist as well. Many of the best examples
Concluding Remarks: An Exciting Time for Studies of GRN Evolution
Deep regulatory homologies at distances where genomes have diverged too far to make use of sequence alignment – even transphyletically – have been reported previously 47, 52, but the challenges inherent in identifying homologous CRMs have kept examples to a minimum (see Outstanding Questions). Furthermore, conservation of function does not always mean conservation of mechanism. Several studies have reported instances of CRMs with related functions that contain similar TF-binding sites, but
Acknowledgments
The author thanks Yoshinori Tomoyasu and Courtney Clark-Hachtel for helpful comments on the manuscript. Support for this work comes from USDA grant 2012-67013-19361 and NIH grant R21 AI125918.
Glossary
- Carinated margin
- an outgrowth of the body wall in the first thoracic segment of beetles such as Tribolium castaneum (red flour beetle). There is evidence to suggest that the carinated margin is a wing serial homolog [24].
- Cis-regulatory module (CRM)
- sequences on DNA that bind TFs to regulate gene expression. Enhancers constitute one common type of CRM.
- Developmental system drift (DSD)
- the phenomenon by which evolutionary changes in genetic pathways do not affect the resultant phenotype.
- Driver and
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Cited by (50)
Measurement and meaning in gene expression evolution
2022, Transcriptome Profiling: Progress and ProspectsPolygenic Adaptation: Integrating Population Genetics and Gene Regulatory Networks
2021, Trends in GeneticsCitation Excerpt :The accumulation of data now allows inferring GRNs and testing hypotheses on their evolution. The different scenarios of GRN evolution are summarized for animals [36] and plants [37] and many cases of selection on GRNs are described [28,38,39]. In parallel, GRN evolution models were developed [40], starting with matrix models simulating how each gene regulates each other and itself [41,42].
Recovering dynamic networks in big static datasets
2021, Physics ReportsCitation Excerpt :First, interactions operating in complex systems and phenomena are not static but unfold in the temporal and spatial dimension [37,38]. In biology, networks among entities have been thought to be an evolving trait, subject to Darwin’s natural selection [39–42]. As such, it is of great interest to reconstruct individualized networks and convert them into context-specific formats for a better understanding of how networks vary with various agents, such as developmental stages, ecological habitats, and cell types [43,44].
Functional genomics of parental care of insects
2020, Hormones and BehaviorCitation Excerpt :Although, DNA methylation looks to play a reduced role regulating the gene expression of insects (see discussion above). Understanding how these factors interact in vivo is necessary to fully characterize the regulation of gene expression through transcriptional regulatory networks (TRNs), or gene regulatory networks (Halfon, 2017; Lu et al., 2017). TRNs are a major target to evolve new phenotypes as they define the sets of genes expressed within a cell and therefore the identity and function of a cell (Simola et al., 2013; Halfon, 2017).