The lab pursues four interrelated research themes:

• Molecular population genetics and evolution (Drosophila and Arabidopsis)
• Functional evolution of cis-regulatory sequences (Drosophila)
• Canalization in development and evolution    (Drosophila)
• Evolutionary dynamics of disease resistance and pathogenicity (Arabidopsis)

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 (http://pondside.uchicago.edu/ecol-evol/faculty/bergelson_j.html). 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 (http://pondside.uchicago.edu/ecol-evol/faculty/borevitz_j.html), 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.

 

Relevant Publications

 

Ludwig, M., N. Patel, and M. Kreitman 1998. Functional conservation of even-skipped stripe 2 enhancer in Drosophila. Development 125:949-958.

Comeron, J. and M. Kreitman, and M. Aguade 1999. Natural selection on synonymous sites is correlated with gene length and recombination rate in Drosophila. Genetics 151(1):239-49.

Stahl, E. A., J. Bergelson, G. Dwyer, R. Mauricio and M. Kreitman 1999. Dynamics of disease resistance polymorphism at the Rpm1 locus of Arabidiposis. Nature 400:667-671.

Ludwig, M.Z, C. Bergman, N.H. Patel and M. Kreitman 2000. Functional evidence for stabilizing selection in a eukaryotic cis-regulatory element. Nature 403:564-567.

Comeron, J. and M. Kreitman 2000. The correlation between intron length and recombination in Drosophila: Dynamic equilibrium between mutation and selective forces. Genetics 156:1175-1190.

Bergelson, J. M. Kreitman, E. A. Stahl and D. Tian 2001. Evolutionary dynamics of plant R-genes. Science 292:2281-2285.

Bergman, C.M. and M. Kreitman 2001. Analysis of conserved noncoding DNA in Drosophila reveals similar constraints in intergenic and intronic sequences. Genome Res. 11(8):1335-45.

Nordborg M., J. O. Borevitz, J. Bergelson, C. C. Berry, J. Chory, J. Hagenblad, M. Kreitman, J. N. Maloof, T. Noyes, P. J. Oefner, E. A. Stahl and D. Weigel 2002. The extent of linkage disequilibrium in Arabidopsis thaliana. Nat Genet. 30:190-193.

Comeron, J. and M. Kreitman 2002. Population, evolutionary and genomic consequences of Iintereference selection. Genetics 161:389-410.

Jakob K. E. M. Gos, H. Araki, T. Van, M. Kreitman and J. Bergelson 2002. Pseudomonas viridiflava and P. syringae – natural pathogens of Arabidopsis thaliana. Mol Plant Microbe Interact. 15: 1195-203.

Toomanian, C. and M. Kreitman 2002. Sequence variation and haplotype structure at the human HFE locus. Genetics 161:1609-23.

Tian, D, H. araki, E. Stahl, J. Bergelson and M. Kreitman 2002. Signature of balancing selection in Arabidopsis. Proc. Natl. Acad. Sci. USA 99:11525-30.

Toomajian, C., R.S. Ajioka, L.B. Jorde, J.P. Kushner and M. Kreitman 2003. A method for detecting recent selection in the human genome from allele age estimates. Genetics 165:287-97.

Tian, D., M.B. Traw, J.Q. Chen, M. Kreitman and J. Bergelson 2003. Fitness costs of R-gene-mediated resistance in Arabidopsis thaliana. Nature 423:74-7.

Mauricio, R., E.A. Stahl, T. Korves, D. Tian, M. Kreitman and J. Bergelson 2003. natural selection for polymorphism in the disease resistance gene Rps2 of Arabidopsis thaliana. Genetics 163:735-46.

Goss, E.M., M. Kreitman and J. Bergelson 2005 Genetic diversity, recombination and cryptic clades of Pseudomonas viridiflava populations of Arabidopsis thaliana. Genetics169:23-35.

Kreitman, M. and A. Di Rienzo 2004. Balancing claims for balancing selection. Trends Genet. 20:300-304.

Ludwig, M., A. Palsson, C. Bergman, E. Alekseeva, J. Nathan and M. Kreitman 2005. Functional evolution of a cis-regulatory module. PloS Biology 3:588-98.

Nordborg, M., T.T. Hu, Y. Ishino, J. Jhaveri, C. Toomajian, H. Zheng, E. Bakker, P. Calabrese, J. Gladstone, R. Goyal, M. Jabobsson, S. Kim, Y. Morozov, B. Padhudasahasram, V. Plagnol, N.A. Rosenberg, C. Shah, J. Wall, J. Wang, K. Zhao, T. Kalbfleisch, V. Schulz, M. Kreitman, J. Bergelson. 2005 The pattern of polymorphism in Arabidopsis thaliana. PloS Biology 3(7) e196.

Araki, H., D. Tian, E.M. Goss, K. Jakob, S.S. Halldosdottir, M. Kreitman and J. Bergelson 2006. Presence/absence polymorphism for alternative pathogenicity islands inPseudomonas viridiflava, a pathogen of Arabidopsis. Proc. Natl. Acad. Sci. USA 103:5887-92.

Bakker E.G., Stahl, E.A., Toomajian, C. Nordborg, M., Kreitman, M. and J.M Bergelson 2006. Distribution of genetic variation within and among local populations of Arabidopsis thaliana over its species range. Mol Ecol. 15:1405-18.

Bakker EG, Toomajian C, Kreitman M, and J Bergelson. A genome-wide survey of R gene polymorphisms in Arabidopsis. Plant Cell 18:1803-18.

Lott, S.E., Kreitman, M., Palsson A., Alekseeva, E. and M.Z. Ludwig 2007. Canalization of segmentation and its evolution in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 104:10926-31.

Araki, H., H. Innan, M. Kreitman and J. Bergelson 2007. Molecular evolution of pathogenicity-island genes in Pleudomonal viridiflava. Genetics 177:1031-41.

Bakker, E.G., Traw M.B., Toomajian C., Kreitman M. and J. Bergelson 2008. Low levels of polymorphism in genes that control the activation of defense response in Arabidopsis thaliana. Genetics 178:2031-43.