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.


Latest News

Subscribe to RSS Feed