title: Dynamic evolution of precise regulatory encodings creates the clustered site signature of enhancers.
abstract: Concentration gradients of morphogenic proteins pattern the embryonic axes of Drosophila by activating different genes at different concentrations. The neurogenic ectoderm enhancers (NEEs) activate different genes at different threshold levels of the Dorsal (Dl) morphogen, which patterns the dorsal/ventral axis. NEEs share a unique arrangement of highly constrained DNA-binding sites for Dl, Twist (Twi), Snail (Sna) and Suppressor of Hairless (Su(H)), and encode the threshold variable in the precise length of DNA that separates one well-defined Dl element from a Twi element. However, NEEs also possess dense clusters of variant Dl sites. Here, we show that these increasingly variant sites are eclipsed relic elements, which were superseded by more recently evolved threshold encodings. Given the divergence in egg size during Drosophila lineage evolution, the observed characteristic clusters of divergent sites indicate a history of frequent selection for changes in threshold responses to the Dl morphogen gradient and confirm the NEE structure/function model.
authors.affiliation: Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Crocker
authors.forename: Nathan
authors.initials: N
authors.lastname: Potter
authors.forename: Albert
authors.initials: A
authors.lastname: Erives
mesh_terms: D000818:Animals; D005075:Biological Evolution; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics* / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; C088731:Su(H) protein, Drosophila; D014157:Transcription Factors; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1; C062236:dl protein, Drosophila; C000604451:sna protein, Drosophila