University of Michigan
Department of Ecology and Evolutionary Biology

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Mentor

Patricia Wittkopp

Fields of study

Understanding evolution of gene regulation and its effects on phenotype

Academic background

B.S. in Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey
Ph.D. in Molecular, Cellular and Developmental Biology, University of Michigan

Research summary

Gene regulation is important for organismal physiology and evolution. Both cis and trans regulatory changes can lead to altered phenotype. In my research, I took a single-gene approach to look at how the sequence, activity and location of cis-regulatory regions called enhancers evolve among Drosophila species. I found that the body and wing enhancers of the yellow gene have altered genomic positions among six different species spanning the Drosophila evolutionary history. In some species these enhancers are located in the 5' of the yellow coding sequence, in some they are in the intron of the gene and in some both regions are sufficient to drive expression in the body and wing epidermal cells. On the other hand, the bristle enhancer was located in the intron in all species. Sequence comparisons failed to find duplicated/translocated regions between the 5' intergenic and intronic sequences hence suggesting a gradual gain and loss transcription factor (TF) binding sites (and other functional sequences) through nucleotide substitutions and small insertion and deletions.

As a result of the above experiments I also saw that yellow 5' intergenic and intronic regions drive expression in elaborate spatial patterns in the pupal wing and body. In order to understand how these enhancer activities function and evolve, I first looked at how they are distributed along the 5' intergenic and intron sequences of yellow from three Drosophila species, D. melagaster, D. pseudoobscura and D. willistoni. I subdivided these regions into 1-kb elements and tested them for enhancer activity using a reporter gene. Concurrently, using yeast-one-hybrid (Y1H) with a comprehensive D. melanogaster TF library, I looked at the transcription factor binding profiles of these 1-kb sub-elements. My goal here is to look at any correlations between similarity in activity, sequence and transcription factor binding, i.e., do enhancers with similar activities bind to similar sets of transcription factors and how does this correlate with sequence similarity and/or homology.

UM affiliation

• Department of Ecology and Evolutionary Biology
• College of Literature, Science, and the Arts