The Dunham lab develops and applies genomic tools to study genome evolution and genetic variation in yeast and humans. We utilize the budding yeasts as a testbed for technology development and as an experimentally tractable system for evolutionary genetics and genomics. By leveraging these systems in creative ways, we hope to learn in molecular detail how cells evolve and the mechanisms by which they do so, addressing important open questions on mutation spectrum, genome structure, mechanisms and consequences of copy number change, genetic interactions, evolution of gene expression, and other fundamental topics.
The lab is broadly organized into an experimental evolution group and a comparative functional genomics group. Many projects also intersect my long-standing interest in how gene and chromosome copy number variation contributes to adaptation, and the mechanisms by which such variation arises. When new technology to study these questions has been required, we have developed it, including methods for genome analysis and long term continuous culture.
Current projects include understanding the costs and benefits of aneuploidy, evolving hybrid yeasts, building new instruments for continuous culture, functionally characterizing centromeres and replication origins across species, and developing high throughput methods for measuring the impact of genetic variation in yeast and humans.
Identification of a novel interspecific hybrid yeast from a metagenomic open fermentation sample using Hi-C. Smukowski Heil C, Burton JN, Liachko I, Friedrich A, Hanson NA, Morris CL, Schacherer J, Shendure J, Thomas JH, Dunham MJ. Yeast. 2018 Jan;35(1):71-84.
The dynamic three-dimensional organization of the diploid yeast genome. Kim S, Liachko I, Brickner DG, Cook K, Noble WS, Brickner JH, Shendure J, Dunham MJ. Elife. 2017 May 24;6. pii: e23623. doi: 10.7554/eLife.23623.
Experimental evolution reveals favored adaptive routes to cell aggregation in yeast. Hope EA, Amorosi CJ, Miller AW, Dang K, Heil CS, Dunham MJ. Genetics. June 1, 2017 vol. 206 no. 2 1153-1167.
Loss of heterozygosity drives adaptation in hybrid yeast. Smukowski Heil CS, DeSevo CG, Pai DA, Tucker CM, Hoang ML, Dunham MJ. Mol Biol Evol. 2017 Jul 1;34(7):1596-1612.
Differential paralog divergence modulates genome evolution across yeast species. Sanchez MR, Miller AW, Liachko I, Sunshine AB, Lynch B, Huang M, Alcantara E, DeSevo CG, Pai DA, Tucker CM, Hoang MJ, Dunham MJ. PLoS Genet. 2017 Feb 14;13(2):e1006585.
High-Throughput Identification of Adaptive Mutations in Experimentally Evolved Yeast Populations. Payen C, Sunshine AB, Ong GT, Pogachar JL, Zhao W, Dunham MJ. PLoS Genetics. 2016; 12(10):e1006339.
Aneuploidy shortens replicative lifespan in Saccharomyces cerevisiae. Sunshine AB, Ong GT, Nickerson DP, Carr D, Murakami CJ, Wasko BM, Shemorry A, Merz AJ, Kaeberlein M, Dunham MJ. Aging Cell. 2016 Jan 13. doi: 10.1111/acel.12443.
The fitness consequences of aneuploidy are driven by condition-dependent gene effects. Sunshine AB, Payen C, Ong GT, Liachko I, Tan KM, Dunham MJ. PLoS Biology. 2015 May 26;13(5):e1002155.
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