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.
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. doi: 10.1371/journal.pbio.1002155. eCollection 2015 May.
The enduring utility of continuous culturing in experimental evolution. Gresham D, Dunham MJ. Genomics. 2014 Oct 2. pii: S0888-7543(14)00192-X. doi: 10.1016/j.ygeno.2014.09.015.
Ploidy-regulated variation in biofilm-related phenotypes in natural isolates of Saccharomyces cerevisiae. Hope EA, Dunham MJ. G3. 2014 Jul 24;4(9):1773-86. doi: 10.1534/g3.114.013250.
Species-Level Deconvolution of Metagenome Assemblies with Hi-C-Based Contact Probability Maps. Burton JN, Liachko I, Dunham MJ, Shendure J. G3. 2014 May 22;4(7):1339-46. doi: 10.1534/g3.114.011825.
The Dynamics of Diverse Segmental Amplifications in Populations of Saccharomyces cerevisiae Adapting to Strong Selection. Payen C, Di Rienzi SC, Ong GT, Pogachar JL, Sanchez JC, Sunshine AB, Raghuraman MK, Brewer BJ, Dunham MJ. G3. 2014 Mar 20;4(3):399-409. doi: 10.1534/g3.113.009365.
GC-rich DNA elements enable replication origin activity in the methylotrophic yeast Pichia pastoris. Liachko I, Youngblood RA, Tsui K, Bubb KL, Queitsch C, Raghuraman MK, Nislow C, Brewer BJ, Dunham MJ. PLoS Genet. 2014 Mar 6;10(3):e1004169. doi: 10.1371/journal.pgen.1004169. eCollection 2014 Mar.
Contemporary, yeast-based approaches to understanding human genetic variation. Dunham MJ, Fowler DM. Curr Opin Genet Dev. 2013 Nov 16. doi:pii: S0959-437X(13)00136-6. 10.1016/j.gde.2013.10.001.
A New System for Comparative Functional Genomics of Saccharomyces Yeasts. Caudy AA, Guan Y, Jia Y, Hansen C, Desevo C, Hayes AP, Agee J, Alvarez-Dominguez JR, Arellano H, Barrett D, Bauerle C, Bisaria N, Bradley PH, Breunig JS, Bush EC, Cappel DA, Capra E, Chen W, Clore J, Combs PA, Doucette C, Demuren O, Fellowes P, Freeman S, Frenkel E, Gadala-Maria D, Gawande R, Glass D, Grossberg S, Gupta A, Hammonds-Odie L, Hoisos A, Hsi J, Hsu YH, Inukai S, Karczewski KJ, Ke X, Kojima M, Leachman S, Lieber D, Liebowitz A, Liu J, Liu Y, Martin T, Mena J, Mendoza R, Myhrvold C, Millian C, Pfau S, Raj S, Rich M, Rokicki J, Rounds W, Salazar M, Salesi M, Sharma R, Silverman SJ, Singer C, Sinha S, Staller M, Stern P, Tang H, Weeks S, Weidmann M, Wolf A, Young C, Yuan J, Crutchfield C, McClean MN, Murphy CT, Llinás M, Botstein D, Troyanskaya OG, Dunham MJ. Genetics. 2013 Sep;195(1):275-87.
High-resolution mapping, characterization, and optimization of autonomously replicating sequences in yeast. Liachko I, Youngblood RA, Keich U, Dunham MJ. Genome Res. 2013 Apr;23(4):698-704.
Design and use of multiplexed chemostat arrays. Miller AW, Befort C, Mitchell E, Dunham MJ. J Vis Exp. 2013 (72).
Origin-dependent inverted-repeat amplification: a replication-based model for generating palindromic amplicons. Brewer BJ, Payen C, Raghuraman MK, Dunham MJ. PLoS Genet. 2011 Mar;7(3):e1002016.
Identification of Aneuploidy-tolerating Mutations. Torres EM, Dephoure N, Panneerselvam A, Tucker CM, Whittaker C, Gygi SP, Dunham MJ, Amon A. Cell. 2010 Oct 1;143(1):71-83.
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