UW Genome Sciences

Research:

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.

Selected Publications:

Experimental evolution of S. cerevisiae for caffeine tolerance alters multidrug resistance and TOR signaling pathways. Geck RC, Moresi NG, Anderson LM; yEvo Students; Brewer R, Renz TR, Taylor MB, Dunham MJ. G3. 2024 Jul 11:jkae148. doi: 10.1093/g3journal/jkae148. [Pubmed][G3][SRA][GitHub][PDF][bioRxiv]

Systematic profiling of ale yeast protein dynamics across fermentation and repitching. Garge RK, Geck RC, Armstrong JO, Dunn B, Boutz DR, Battenhouse A, Leutert M, Dang V, Jiang P, Kwiatkowski D, Peiser T, McElroy H, Marcotte EM, Dunham MJ. G3. 2024 Mar 6;14(3):jkad293. doi: 10.1093/g3journal/jkad293. PMID: 38135291 [Pubmed][G3][Shiny App][PDF][bioRxiv][Genes to Genomes blog][The Brü Lab podcast]

yEvo: a modular eukaryotic genetics and evolution research experience for high school students. Taylor MB*, Warwick AR*, Skophammer R, Boyer JM, Geck RC, Gunkelman K, Walson M, Rowley PA#, Dunham MJ# (*co-first authors, #co-corresponding authors). Ecol Evol. 2024 Jan 7;14(1):e10811. doi: 10.1002/ece3.10811. eCollection 2024 Jan. PMID: 38192907 [Pubmed][Ecology and Evolution][PDF][bioRxiv]

Caffeine-tolerant mutations selected through an at-home yeast experimental evolution teaching lab. Moresi NG, Geck RC, Skophammer R, Godin D, yEvo Students, Taylor MB, Dunham MJ. MicroPubl Biol. 2023 Feb 9;2023:10.17912/micropub.biology.000749. doi: 10.17912/micropub.biology.000749. eCollection 2023. PMID: 36855741 [Pubmed][microPublication Biology][PDF][bioRxiv][This Week in Microbiology podcast]

Functional interpretation, cataloging, and analysis of 1,341 glucose-6-phosphate dehydrogenase variants. Geck RC, Powell NR, Dunham MJ. AJHG. 2023 Feb 2;110:1–12. [Pubmed][AJHG][G6PDcat on GitHub][PDF][letter to the editor response][GitHub][PDF][bioRxiv][All of Us][All of Us in Spanish]

yEvo: Experimental evolution in high school classrooms selects for novel mutations and epistatic interactions that impact clotrimazole resistance in S. cerevisiae. Taylor MB, Skophammer R, Warwick AR, Geck RC, Boyer JM, yEvo Students, Walson M, Large CRL, Hickey AS, Rowley PA#, Dunham MJ# (#co-corresponding authors). G3. 2022 Nov 4;12(11):jkac246. doi: 10.1093/g3journal/jkac246. [Pubmed][G3][PDF][SRA][bioRxiv]

PacRAT: a program to improve barcode-variant mapping from PacBio long reads using multiple sequence alignment. Yeh CC*, Amorosi CJ*, Showman S, Dunham MJ. (*co-first authors). Bioinformatics. 2022 May 13;38(10):2927-2929. doi: 10.1093/bioinformatics/btac165. [Pubmed][Bioinformatics][GitHub][bioRxiv]

Massively parallel characterization of CYP2C9 variant enzyme activity and abundance. Amorosi CJ, Chiasson MA, McDonald MG, Wong LH, Sitko KA, Boyle G, Kowalski JP, Rettie AE, Fowler DM#, Dunham MJ# (co-corresponding authors). Am J Hum Genet. 2021 Sep 2;108(9):1735-1751. doi: 10.1016/j.ajhg.2021.07.001. [Pubmed][AJHG][PDF][bioRxiv][Science in Seattle]

Multiplexing Mutation Rate Assessment: Determining Pathogenicity of Msh2 Variants in S. cerevisiae. Ollodart AR, Yeh CC, Miller AW, Shirts BH, Gordon AS, Dunham MJ. Genetics. 2021 Apr 12;iyab058. doi: 10.1093/genetics/iyab058. [Pubmed][Genetics][PDF][bioRxiv][BioProject]

Transposable element mobilization in interspecific yeast hybrids. Heil CS, Patterson K, Hickey AS, Alcantara E, Dunham MJ. Genome Biol Evol. 2021 Mar 1;13(3):evab033. doi: 10.1093/gbe/evab033. [Pubmed][GBE][PMC][PDF][bioRxiv][BioProject]

additional publications available via Google Scholar