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Invited Speaker: He Bin

Cis Regulatory Variation in Drosophila : the evolutionary forces drivingTF binding sites turnover and the underpinning of a complex trait
When Mar 22, 2012
from 02:00 PM to 03:00 PM
Where C101,IOZ
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Bin He is a Ph.D. student working with Marty Kreitman in the department of Ecology and Evolution at the Univeristy of Chicago. He received his B.S. degree in life sciences from Peking University in 2006, working on bacterial persistence in Prof. Ouyang Qi's lab. In his graduate work, he used a combination of population genetics and experimental approaches to identify the evolutionary forces shaping natural variation patterns, particularly in cis-regulatory regions (He 2011). He is currently developing a novel system to use Drosophila as a model to dissect the genetic basis for complex traits.
In this talk I will present two studies utilizing Drosophila natural variations. In the first part, I
will investigate the puzzling phenomenon of a fast turnover (gain and loss) of transcription factor binding sites, despite the fact that many of the enhancers in which these binding sites were discovered have strongly conserved expression patterns over even 100 million years. Using population genetics approaches, I found that the previously accepted model of a strictly neutral process is not consistent with the data. Instead, both polymorphism and divergence patterns strongly suggest that natural selection, both positive and negative, drives the gain as well as loss of binding sites. These results led us to propose that fine-tuning of gene expression is frequently employed in adaptation. In the second part, I will talk about how we use Drosophila natural variation to explore the genetic basis of complex (disease) traits. We created a model for mis-folded protein disease by expressing a mutant human insulin gene in the fly eye imaginal discs, which caused eye degeneration. This disease phenotype is strongly modified when the transgenic line is crossed to a wild caught population of flies that have been subsequently inbred and whole genome sequenced. The latter allowed us to perform a genome-wide association study, through which we identified common variants in a precisely mapped region within the intron of a gene. Genetic knockdown of the gene verified its role in modifying the phenotype, and expression analysis suggested a regulatory effect of the candidate variation. This study demonstrated the power of using a model organism approach to dissect the genetic basis of complex (disease) traits.