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Evolution Acts on Enhancer Organization to Fine-Tune Gradient Threshold Readouts
Journal article   Open access

Evolution Acts on Enhancer Organization to Fine-Tune Gradient Threshold Readouts

Justin Crocker, Yoichiro Tamori and Albert Erives
PLoS biology, Vol.6(11), pp.2576-2587
11/2008
DOI: 10.1371/journal.pbio.0060263
PMCID: PMC2577699
PMID: 18986212
url
https://doi.org/10.1371/journal.pbio.0060263View
Published (Version of record) Open Access

Abstract

The elucidation of principles governing evolution of gene regulatory sequence is critical to the study of metazoan diversification. We are therefore exploring the structure and organizational constraints of regulatory sequences by studying functionally equivalent cis -regulatory modules (CRMs) that have been evolving in parallel across several loci. Such an independent dataset allows a multi-locus study that is not hampered by nonfunctional or constrained homology. The neurogenic ectoderm enhancers (NEEs) of Drosophila melanogaster are one such class of coordinately regulated CRMs. The NEEs share a common organization of binding sites and as a set would be useful to study the relationship between CRM organization and CRM activity across evolving lineages. We used the D. melanogaster transgenic system to screen for functional adaptations in the NEEs from divergent drosophilid species. We show that the individual NEE modules across a genome in any one lineage have independently evolved adaptations to compensate for lineage-specific developmental and/or genomic changes. Specifically, we show that both the site composition and the site organization of NEEs have been finely tuned by distinct, lineage-specific selection pressures in each of the three divergent species that we have examined: D. melanogaster , D. pseudoobscura , and D. virilis . Furthermore, by precisely altering the organization of NEEs with different morphogen gradient threshold readouts, we show that CRM organizational evolution is sufficient for explaining changes in enhancer activity. Thus, evolution can act on CRM organization to fine-tune morphogen gradient threshold readouts over a wide dynamic range. Our study demonstrates that equivalence classes of CRMs are powerful tools for detecting lineage-specific adaptations by gene regulatory sequences. Characterizing neuroectodermal enhancers located throughout the genomes of three Drosophila species reveals that each enhancer evolved functional adaptations that compensate for the evolutionary changes specific to each lineage.
Developmental Biology Evolutionary Biology Molecular Biology

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