Evolution Acts On Enhancer Organization To Fine-Tune Gradient Threshold Readouts

The elucidation of principles governing evolution of gene regulatory sequence is critical to the study of metazoan diversification. The authors 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.


The authors used the D. melanogaster transgenic system to screen for functional adaptations in the NEEs
from divergent drosophilid species. They 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, they 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. Their study demonstrates that equivalence
classes of CRMs are powerful tools for detecting lineage-specific adaptations by gene regulatory sequences.



"Evolution acts on enhancer organization to fine-tune gradient threshold readouts."
Crocker J, Tamori Y, Erives A (2008)

PLoS Biol 6(11): e263. doi:10.1371/journal.pbio.0060263

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