CCSB group meeting: “Hopeful monsters? Evolution and synthetic biology of the eve stripe 2 enhancer”


Carlos Martinez and John Reinitz


June 2, 2011, 1:00 pm – 2:00 pm


Room: 10260


University of Chicago
Knapp Center for Biomedical Discovery (KCBD)
900 E. 57th Street, 10 floor - Room 10260
Chicago, IL

Northwestern University
Silverman Hall Room 2-510
2170 Campus Dr.
Evanston, IL 60208

We have developed a novel computational approach for the custom design of complex cis-regulatory regions, as well as methods for predicting the evolution and putative ancestral sequences of extant enhancers in Drosophila.  Our methodology involves the use of a feed forward transcriptional model, capable of predicting gene expression patterns directly from enhancer sequence, as a tool for enhancer design and to provide a functional constraint for predicting enhancer evolution.  In the former case, enhancer design was achieved through the use of simulated annealing in conjunction with a transcriptional model in order to efficiently search the sequence space for novel enhancers having the desired expression pattern.  For the latter, Bayesian inference was used to generate a set of possible ancestral eve S2E enhancer sequences for the sim-sec, mel-sim-sec, and ere-yak internal nodes of the Drosophila phylogenetic tree.  Candidate ancestral sequences were selected for synthesis and experimental validation by checking the model predicted expression patterns of each sequence against a reference eve stripe 2 expression pattern.  In addition, we synthesized and tested two S2E ancestral sequences predicted to lie at midway points along a neutral evolutionary path going from the mel-sim-sec ancestor to mel, and from the ere-yak ancestor to ere.  For this purpose, we have used a neutral evolutionary algorithm (NEA) which seeks to find evolutionary pathways between functionally conserved enhancers that do not change the transcription pattern at any point along the path.


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