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Variation between long-diverged species. Eukaryotes specialize to their environment in amazing ways. When a species from one niche differs radically from its relatives elsewhere, we would love to know the mechanism at play. In many cases the underlying adaptive alleles are a mystery, especially if they arose long ago. The main roadblock to date has been that most experimental tools in evolutionary genetics research are only applicable to comparison across strains, not species. Ongoing work in the lab is devoted to breaking through this limitation. We have developed RH-seq, a novel approach to map the genetic basis of differences between distantly related species. Our strategy is designed to reveal the nucleotide-level variants that a given species has used to adapt to its environment over evolutionary time. We piloted RH-seq using thermotolerance in Saccharomyces as a test case; current projects focus on other phenotypes in this model organism, other fungi, and in reproductively isolated mice.
Mapping genotype to phenotype in fungi. Most fungal genomes are poorly annotated, so we have no idea of the genetic architecture for many fungal traits of industrial and biomedical relevance. In published work, our lab has used variation across wild populations to find the molecular basis of morphology traits in the model fungi Saccharomyces and Neurospora; we have also developed genomic screening approaches to annotate candidate virulence islands in the plant pathogen Zymoseptoria and lipid metabolism genes in the oleaginous yeast Rhodosporidium. Our next project, now in progress, is focused on strain variation in virulence and stress resistance traits in the human pathogen Coccidioides.
Jin KA, Wilson KA, Beck JN, Nelson CS, Brownridge GW, Harrison B, Djukovic D, Raftery D, Brem RB, Yu S, Drton M, Shojae A, Kapahi P, Promislow D. Genetic and metabolomic architecture of variation in diet-restriction-mediated lifespan extension in Drosophila. PLoS Genetics, in press, 2020.
Wilson KA, Beck JN, Nelson CS, Hilsabeck TA, Promislow D, Brem RB, Kapahi P. Genome-wide analyses for lifespan and healthspan in D. melanogaster reveal decima as a regulator of insulin-like peptide production. Current Biology, S0960-9822(20)30659-X, 2020.
Dubin CA, Roop JI, Brem RB. Divergence of Peroxisome Membrane Gene Sequence and Expression Between Yeast Species. G3 10(6):2079-2085, 2020.
Weiss CV, Brem RB. Dissecting Trait Variation across Species Barriers. Trends in Ecology and Evolution 34(12):1131-1136, 2019.
Walsh CM, Hill RZ, Schwendinger-Schreck J, Deguine J, Brock EC, Kucirek N, Rifi Z, Wei J, Gronert K, Brem RB, Barton GM, Bautista DM. Neutrophils promote CXCR3-dependent itch in the development of atopic dermatitis. Elife 8:e48448, 2019.
Weiss CV, Chuong JN, Brem RB. Genetic Mapping of Thermotolerance Differences Between Species of Saccharomyces Yeast via Genome-Wide Reciprocal Hemizygosity Analysis. Journal of Visualized Experiments (150), 2019.
Sasikumar AN, Killilea DW, Kennedy BK, Brem RB. Potassium restriction boosts vacuolar acidity and extends lifespan in yeast. Experimental Gerontology, 120:101-106, 2019.
Sanchez MR, Payen C, Cheong F, Hovde BT, Bissonnette S, Arkin AP, Skerker JM, Brem RB, Caudy AA, Dunham MJ. Transposon insertional mutagenesis in Saccharomyces uvarum reveals trans-acting effects influencing species-dependent essential genes. Genome Research 29(3):396-406, 2019.
Weiss CV, Roop JI, Hackley RK, Chuong JN, Grigoriev IV, Arkin AP, Skerker JM, Brem RB. Genetic dissection of an ancient divergence in yeast thermotolerance. Nature Genetics 50(11):1501-1504, 2018. Featured article, Science, Nov 2, 2018 issue; Faculty of 1000 Recommended Paper.
Hill RZ, Hoffman B, Morita T, Campos SM, Lumpkin EA, Brem RB, Bautista DM. The signaling lipid sphingosine-1-phosphate regulates mechanical pain. eLife 7:e33285, 2018.
Coradetti ST, Pinel D, Geiselman G, Ito M, Mondo S, Reilly MC, Cheng YF, Bauer S, Grigoriev I, Gladden JM, Simmons BA, Brem RB, Arkin AP, Skerker JM. Functional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides. eLife 7:e32110, 2018. Featured article, eLife Digest.
Bay RA, Rose N, Barrett R, Bernatchez L, Ghalambour CK, Lasky JR, Brem RB, Palumbi SR, Ralph P. Predicting evolutionary responses to contemporary environmental change using population genomic data. American Naturalist 189(5):463-473, 2017.
Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila. Nelson CS, Beck JN, Wilson KA, Pilcher ER, Kapahi P, Brem RB. BMC Genomics 17(1):867, 2016.
Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1. Mark KA, Dumas KJ, Bhaumik D, Schilling B, Davis S, Oron TR, Sorensen DJ, Lucanic M, Brem RB, Melov S, Ramanathan A, Gibson BW, Lithgow GJ. Cell Reports 17(5):1226-1237.
The role of transcription factors at antisense-expressing gene pairs in yeast. Mostovoy Y, Thiemicke A, Hsu TY, Brem RB. Genome Biology and Evolution 8(6):1748-61, 2016.
Polygenic evolution of a sugar specialization tradeoff in yeast. Roop JI, Chung KC, Brem RB. Nature 530(7590):336-9, 2016. Featured article in Cell Systems, March 2016 issue.
Katewa SD, Akagi K, Bose N, Rakshit K, Camarella T, Zheng X, Hall D, Davies S, Nelson C, Brem RB, Ramanathan A, Sehgal A, Giebultowicz JM, Kapahi P. Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila. Cell Metabolism 23(1):143-54, 2016.
McCormick M, … Brem RB, … Kennedy BK. A comprehensive analysis of replicative lifespan in 4,698 single-gene deletion strains uncovers novel mechanisms of aging. Cell Metabolism 22(5):895-906, 2015.
Morita T, McClain SP, Batia LM, Pellegrino M, Wilson SR, Kienzler MA, Lyman K, Olsen ASB, Wong JF, Brem RB, Bautista DM. HTR7 is a transducer of serotonergic acute and chronic itch. Neuron 87(1):124-38, 2015.
Kellner R, Bhattacharyya A, Poppe S, Hsu TY, Brem RB, Stukenbrock E. Transcriptome sequencing at early-stage infection of the wheat pathogen Z. tritici reveals chromosome differences in transcription patterns and host-specific gene expression. Genome Biology and Evolution 6(6):1353-65, 2014.
Ellison CE, Kowbel D, Glass NL, Taylor JW, Brem RB. Discovering functions of unannotated genes from a transcriptome survey of wild fungal isolates. mBio 5(2):e01046-13, 2014.
Schraiber JG, Mostovoy Y, Hsu TY, Brem RB. Inferring pathway evolutionary histories from transcriptional profiling data. PLoS Computational Biology 9(10):e1003255, 2013.
Palma-Guerrero J, Hall CR, Kowbel D, Welch J, Taylor JW, Brem RB, Glass NL. Genome-wide association identifies novel loci involved in fungal communication. PLoS Genetics 9(8):e1003669, 2013.
Lee HN, Mostovoy Y, Hsu TY, Chang A, Brem RB. Divergence of iron metabolism in wild Malaysian yeast. G3: Genes|Genomes|Genetics 3(12):2187-94, 2013.
Roop JI, Brem RB. Rare variants in hypermutable genes underlie common morphology and growth traits in wild S. paradoxus yeasts. Genetics 195(2):513-525, 2013. Cover article, July 2014 issue; featured paper, October 2013 issue highlights.
Yoon OK, Hsu TY, Im JH, Brem RB. Genetics and regulatory impact of alternative polyadenylation in human B-lymphoblastoid cells. PLoS Genetics 8(8):e1002882, 2012.
Martin HC, Roop JI, Schraiber JG, Hsu TY, Brem RB. Evolution of a membrane protein regulon in Saccharomyces. Molecular Biology and Evolution, 29(7):1747-1756, 2012.
Denby CM, Im JH, Yu RC, Pesce CG, Brem RB. Negative feedback confers mutational robustness in yeast transcription factor regulation. PNAS 109(10):3874-8, 2012.
Zhu J, Sova P, Xu Q, Dombek KM, Xu EY, Vu H, Tu Z, Brem RB, Bumgarner RE, Schadt EE. Stitching together multiple data dimensions reveals interacting metabolic and transcriptomic networks that modulate cell regulation. PLoS Biology 10(4):e1001301, 2012.
Ellison CE, Hall C, Kowbel D, Welch J, Brem RB, Glass NG, Taylor JW. Population genomics and local adaptation in wild isolates of a model microbial eukaryote. PNAS 108(7):2831-6, 2011. Faculty of 1000 Must Read/Recommended Paper.
Lee HN, Magwene PM, Brem RB. Natural variation in CDC28 underlies morphological phenotypes in an environmental yeast isolate. Genetics 188(3):723-30, 2011.
Bullard JH, Mostovoy J, Dudoit S, Brem RB. Polygenic and directional regulatory evolution across pathways in Saccharomyces. PNAS 107(11):5058-5063, 2010.
Yoon OK, Brem RB. Non-canonical transcript forms in yeast and their regulation during environmental stress. RNA 16(6):1256-67, 2010. Faculty of 1000 Recommended Paper.