The Dunham Lab combines experimental evolution with genomic analysis to study the structure and function of genetic networks in yeast. Cultures of S. cerevisiae can be maintained for hundreds of generations of nutrient-limited, steady-state growth in chemostats. During this time, more fit mutants appear and sweep through the culture. By comparing the "evolved" strains to the ancestral founders, we can study the adaptations selected in the chemostat. Growth phenotypes, cell morphology, global gene expression, and other parameters all change during the course of chemostat evolution. Genetic dissection of the small number of mutations responsible for these many changes should allow us to recognize the rate limiting steps and control points governing the cells' response to long-term, narrow selection.
Using new microarray-based technologies developed by my lab and collaborators, we can now look genome-wide for copy number changes, point mutations, and transposon insertions. In addition, classical genetic approaches and a novel mapping technique are being employed to dissect the features of the evolved strains.
Further work on these mutations will determine their exact fitness consequences, for example, which genes in the aneuploid regions contribute to fitness. Since these events so closely resemble the types of aneuploidies almost universally observed in cancers, we hope the work will be of broader interest. We have further explored this connection through studying lab-created aneuploid strains.
Finally, we have started to study "real" evolution by looking at the functional divergence between S. cerevisiae and a sister yeast, S. bayanus. Hybrids between these species evolve in novel ways and may teach us something about whole genome duplications and the evolution of duplicate genes.
Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M, Dunham MJ and Amon A. Science. 2007 Aug 17;317(5840):916-24.
Viewing the Larger Context of Genomic Horizontal Integration. Matthew Hibbs, Grant Wallace, Maitreya Dunham, Kai Li, and Olga Troyanskaya. Proceedings of the 11th Int. Conf. on Information Visualization (IV07), 2007.
Global Mapping of Transposon Location. Gabriel A, Dapprich J, Kunkel M, Gresham D, Pratt SC, Dunham MJ. PLoS Genet. 2006 Dec 15;2(12):e212.
Functional analysis of gene duplications in Saccharomyces cerevisiae. Guan Y, Dunham MJ, Troyanskaya OG. Genetics. 2006 Dec 6.
Mapping Novel Traits by Array-assisted Bulk Segregant Analysis in Saccharomyces cerevisiae. Brauer MJ, Christianson CM, Pai DA, Dunham MJ. Genetics. 2006 Jul;173(3):1813-6. Epub 2006 Apr 19.
Genome-wide detection of polymorphisms at nucleotide resolution with a single DNA microarray. Gresham D, Ruderfer DM, Pratt SC, Schacherer J, Dunham MJ, Botstein D, Kruglyak L. Science. 2006 Mar 31;311(5769):1932-6. Epub 2006 Mar 9.
Accurate detection of aneuploidies in array CGH and gene expression microarray data. Myers CL, Dunham MJ, Kung SY, Troyanskaya OG. Bioinformatics. 2004 Dec 12;20(18):3533-43. Epub 2004 Jul 29.
Characteristic Genome Rearrangements in Experimental Evolution of S. cerevisiae. Dunham MJ, Badrane H, Ferea T, Adams J, Brown PO, Rosenzweig RF, Botstein D. Proc Natl Acad Sci USA. 2002 Dec 10;99(25):16144-9.
Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions. Haab BB, Dunham MJ, Brown PO. Genome Biology. 2001;2(2):RESEARCH0004.