Kreitman:Research

From OpenWetWare

Revision as of 03:01, 4 December 2008 by Bin He (Talk | contribs)
Jump to: navigation, search

Image:Top_banner.tif


     Home        Research        Internal        Lab Members        Publications        Protocol        Contact       

Description

I have had a longstanding interest in molecular population genetics, and have contributed over the years to the development of methods for analyzing DNA sequence polymorphism and evolutionary data, particularly with respect to detecting the action of natural selection. Although our work has historically focused on Drosophila, we have shifted our attention in recent years to Arabidopsis thaliana and its bacterial pathogens (in collaboration with Joy Bergelson's lab). Plant resistance to bacterial disease and bacterial pathenogenicity is an immensely powerful system for investigating both the ecological and evolutionary contexts of molecular adaptation, and holds the promise of uniting the two. In collaboration with Magnus Nordborg (http://walnut.usc.edu/) and Justin Borevitz, we have completed genome-wide assessments of genetic polymorphism, have assembled at 250K SNP chip, and have genotyped hundreds of isolines derived from natural populations. We have validated genome-wide association mapping in Arabidopsis to discover disease resistance polymorphism, and intend to do the same with common bacterial pathogens. We are also carrying out metagenomic surveys of the bacterial pathogen community infecting Arabidopsis.

Ever since our early studies of sequence variation and evolution in Drosophila, including noncoding regions, we have been interested in the contribution of gene regulation to adaptation. Drawing on extensive molecular analysis of the Drosophila even-skipped stripe two enhancer (eS2E) -- arguably the best characterized of any eukaryotic cis-regulatory sequence -- and a rich knowledge of the segmentation process in embryogenesis, Dr. Michael Ludwig (UC) and I have embarked on a research program to functionally dissect the evolution of this enhancer. Our approach has been to exploit transformation technology and the extensive molecular genetic arsenal available for the fly to quantitatively investigate evolved differences in eS2E performance. We are currently investigating features of the eS2E structural architecture that might contribute to functional robustness in enhancer performance, and the evolution of these features. We are also investigating developmental canalization of the segmentation process and the ability of the system to evolve in the face of this canalization. Finally, with the availability of a dozen Drosophila genome sequences, and genome-wide polymorphism data, we are functionally characterizing polymorphic and fixed differences in transcription factor binding sites with the goal of developing novel statistical methods to evaluate mechanisms of selection acting on binding site evolution.

Egg size variation

Drosophila Transcriptional Enhancers Evolution

Personal tools