@article{f2aa2fdb6e834d3bab9512d3b66f8c22,
title = "Development of a Comprehensive Genotype-to-Fitness Map of Adaptation-Driving Mutations in Yeast",
abstract = "Adaptive evolution plays a large role in generating the phenotypic diversity observed in nature, yet current methods are impractical for characterizing the molecular basis and fitness effects of large numbers of individual adaptive mutations. Here, we used a DNA barcoding approach to generate the genotype-to-fitness map for adaptation-driving mutations from a Saccharomyces cerevisiae population experimentally evolved by serial transfer under limiting glucose. We isolated and measured the fitness of thousands of independent adaptive clones and sequenced the genomes of hundreds of clones. We found only two major classes of adaptive mutations: self-diploidization and mutations in the nutrient-responsive Ras/PKA and TOR/Sch9 pathways. Our large sample size and precision of measurement allowed us to determine that there are significant differences in fitness between mutations in different genes, between different paralogs, and even between different classes of mutations within the same gene.",
author = "Sandeep Venkataram and Barbara Dunn and Yuping Li and Atish Agarwala and Jessica Chang and Ebel, {Emily R.} and Kerry Geiler-Samerotte and Lucas H{\'e}rissant and Blundell, {Jamie R.} and Levy, {Sasha F.} and Fisher, {Daniel S.} and Gavin Sherlock and Petrov, {Dmitri A.}",
note = "Funding Information: We wish to thank all members of the D.A.P., G.S., and D.S.F. labs for useful discussions, and Michael Desai, Sergey Kryazhimskiy, Katja Schwartz, Dave Yuan, and Jake Cherry for technical help. We thank the Stanford Shared FACS facility for use of their flow cytometers, and the Stanford Center for Personalized Genomics and Medicine and NextSEQ for Illumina sequencing services. S.V. is supported by NIH/NHGRI T32 HG000044 and the Stanford Center for Computational, Human and Evolutionary Genomics (CEHG); E.E. by NSF GFRP DGE-1247312; J.C. by NSF GRFP DGE-114747; A.A. by a Stanford Bio-X Bowes Fellowship; L.H. by NIH grant R01 GM110275 and a fellowship from CEHG; J.B. and S.F.L. by the Louis and Beatrice Laufer Center; and D.S.F. by NSF PHY-1305433 and NIH R01 HG003328. The work was supported by NIH grants R01 HG003328 and GM110275 to G.S. and R01 GM115919, GM10036601, and GM097415 to D.A.P. Data were collected on an instrument in the Shared FACS Facility obtained using NIH S10 Shared Instrument grant RR027431. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = sep,
day = "8",
doi = "10.1016/j.cell.2016.08.002",
language = "English (US)",
volume = "166",
pages = "1585--1596.e22",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",
}