title: The 100-genomes strains, an S. cerevisiae resource that illuminates its natural phenotypic and genotypic variation and emergence as an opportunistic pathogen.
abstract: Saccharomyces cerevisiae, a well-established model for species as diverse as humans and pathogenic fungi, is more recently a model for population and quantitative genetics. S. cerevisiae is found in multiple environments-one of which is the human body-as an opportunistic pathogen. To aid in the understanding of the S. cerevisiae population and quantitative genetics, as well as its emergence as an opportunistic pathogen, we sequenced, de novo assembled, and extensively manually edited and annotated the genomes of 93 S. cerevisiae strains from multiple geographic and environmental origins, including many clinical origin strains. These 93 S. cerevisiae strains, the genomes of which are near-reference quality, together with seven previously sequenced strains, constitute a novel genetic resource, the "100-genomes" strains. Our sequencing coverage, high-quality assemblies, and annotation provide unprecedented opportunities for detailed interrogation of complex genomic loci, examples of which we demonstrate. We found most phenotypic variation to be quantitative and identified population, genotype, and phenotype associations. Importantly, we identified clinical origin associations. For example, we found that an introgressed PDR5 was present exclusively in clinical origin mosaic group strains; that the mosaic group was significantly enriched for clinical origin strains; and that clinical origin strains were much more copper resistant, suggesting that copper resistance contributes to fitness in the human host. The 100-genomes strains are a novel, multipurpose resource to advance the study of S. cerevisiae population genetics, quantitative genetics, and the emergence of an opportunistic pathogen.
authors.affiliation: Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, North Carolina 27710, USA;
authors.forename: Pooja K
authors.initials: PK
authors.lastname: Strope
authors.affiliation: Department of Biology, Duke University, Durham, North Carolina 27710, USA;
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Skelly
authors.affiliation: Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, North Carolina 27710, USA;
authors.forename: Stanislav G
authors.initials: SG
authors.lastname: Kozmin
authors.affiliation: Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, North Carolina 27710, USA;
authors.forename: Gayathri
authors.initials: G
authors.lastname: Mahadevan
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Stone
authors.affiliation: Department of Biology, Duke University, Durham, North Carolina 27710, USA;
authors.forename: Paul M
authors.initials: PM
authors.lastname: Magwene
authors.affiliation: Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, North Carolina 27710, USA;
authors.forename: Fred S
authors.initials: FS
authors.lastname: Dietrich
authors.affiliation: Duke University Medical Center, Department of Molecular Genetics and Microbiology, Durham, North Carolina 27710, USA;
authors.forename: John H
authors.initials: JH
authors.lastname: McCusker
mesh_terms: D020451:Contig Mapping / Q000379:methods*; D016681:Genome, Fungal; D005838:Genotype; D010641:Phenotype; D010802:Phylogeny; D011110:Polymorphism, Genetic; D012441:Saccharomyces cerevisiae / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D016415:Sequence Alignment / Q000379:methods*; D014774:Virulence / Q000235:genetics
references.citation: G3 (Bethesda). 2014 Mar;4(3):389-98
references.pmid: 24374639
references.citation: G3 (Bethesda). 2013 Apr 9;3(4):665-673
references.pmid: 23550117
references.citation: Int J Food Microbiol. 2007 Dec 15;120(3):217-24
references.pmid: 17976849
references.citation: Genome Res. 2003 Apr;13(4):721-31
references.pmid: 12654723
references.citation: PLoS One. 2010;5(6):e11309
references.pmid: 20593017
references.citation: Diagn Microbiol Infect Dis. 2010 Nov;68(3):220-7
references.pmid: 20846806
references.citation: Science. 1996 Oct 25;274(5287):546, 563-7
references.pmid: 8849441
references.citation: Genetics. 2000 Jun;155(2):945-59
references.pmid: 10835412
references.citation: J Hosp Infect. 2002 Dec;52(4):268-72
references.pmid: 12473471
references.citation: PLoS Genet. 2013;9(9):e1003771
references.pmid: 24039607
references.citation: Genome Res. 2012 May;22(5):908-24
references.pmid: 22369888
references.citation: Proc Natl Acad Sci U S A. 1982 Sep;79(17):5342-6
references.pmid: 6291039
references.citation: Cell Host Microbe. 2013 Mar 13;13(3):265-76
references.pmid: 23498952
references.citation: Res Microbiol. 1999 Apr;150(3):199-204
references.pmid: 10229949
references.citation: Environ Pollut. 2012 Aug;167:16-26
references.pmid: 22522314
references.citation: Med Mycol. 2004 Aug;42(4):333-9
references.pmid: 15473358
references.citation: J Hosp Infect. 2000 Aug;45(4):293-301
references.pmid: 10973747
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1987-92
references.pmid: 21245305
references.citation: Science. 1998 Aug 21;281(5380):1194-7
references.pmid: 9712584
references.citation: Microbes Infect. 2003 Jun;5(7):685-90
references.pmid: 12787745
references.citation: Science. 2010 Apr 23;328(5977):469
references.pmid: 20413493
references.citation: Genetics. 1986 May;113(1):35-43
references.pmid: 3519363
references.citation: J Infect. 2012 Jan;64(1):68-75
references.pmid: 22101079
references.citation: PLoS Genet. 2008 Aug;4(8):e1000183
references.pmid: 18769710
references.citation: PLoS Genet. 2010 Sep;6(9):e1001109
references.pmid: 20838597
references.citation: Genetics. 2012 Aug;191(4):1345-53
references.pmid: 22673807
references.citation: J Basic Microbiol. 1988;28(3):147-60
references.pmid: 3057171
references.citation: Genome Res. 2013 Sep;23(9):1496-504
references.pmid: 23720455
references.citation: G3 (Bethesda). 2013 Dec;3(12):2163-71
references.pmid: 24122055
references.citation: J Biosci. 2010 Mar;35(1):119-26
references.pmid: 20413916
references.citation: Genetics. 1994 Apr;136(4):1261-9
references.pmid: 8013903
references.citation: Lancet Infect Dis. 2011 Feb;11(2):142-51
references.pmid: 21272794
references.citation: Genetics. 2012 Dec;192(4):1503-11
references.pmid: 23023004
references.citation: Mol Ecol. 2012 Nov;21(22):5404-17
references.pmid: 22913817
references.citation: Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13458-63
references.pmid: 22847430
references.citation: Nature. 2009 Mar 19;458(7236):342-5
references.pmid: 19212320
references.citation: PLoS One. 2012;7(10):e46688
references.pmid: 23056405
references.citation: Nature. 2009 Mar 19;458(7236):337-41
references.pmid: 19212322
references.citation: Genome Res. 2002 Oct;12(10):1533-9
references.pmid: 12368245
references.citation: FEMS Yeast Res. 2011 Nov;11(7):587-94
references.pmid: 22093685
references.citation: Crit Rev Microbiol. 2010;36(1):1-53
references.pmid: 20088682
references.citation: Front Cell Infect Microbiol. 2013;3:89
references.pmid: 24350063
references.citation: EMBO J. 1995 Aug 15;14(16):3870-82
references.pmid: 7664728
references.citation: J Clin Microbiol. 2001 Feb;39(2):551-9
references.pmid: 11158105
references.citation: Science. 1985 May 10;228(4700):685-90
references.pmid: 3887570
references.citation: FEMS Yeast Res. 2009 Feb;9(1):143-52
references.pmid: 19054123
references.citation: Mol Ecol. 2009 Jul;18(13):2779-86
references.pmid: 19457175
references.citation: J Clin Microbiol. 2007 Jun;45(6):1735-45
references.pmid: 17442797
references.citation: Adv Exp Med Biol. 2014;781:37-48
references.pmid: 24277294
references.citation: Yeast. 2002 Oct;19(14):1261-76
references.pmid: 12271461
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: Clin Infect Dis. 2005 Jun 1;40(11):1625-34
references.pmid: 15889360
references.citation: Mol Gen Genet. 1991 May;227(1):149-54
references.pmid: 2046655
references.citation: J Biol Chem. 2012 Apr 20;287(17):13549-55
references.pmid: 22389498
references.citation: Curr Med Chem. 2005;12(18):2163-75
references.pmid: 16101497
references.citation: J Clin Microbiol. 1996 Dec;34(12):3031-4
references.pmid: 8940443
references.citation: Med Mycol. 2000;38 Suppl 1:225-36
references.pmid: 11204149
references.citation: G3 (Bethesda). 2014 Nov;4(11):2259-69
references.pmid: 25236733
references.citation: J Clin Microbiol. 2009 Jan;47(1):117-23
references.pmid: 19005141
references.citation: FEBS Lett. 1991 Oct 21;291(2):189-91
references.pmid: 1657642
references.citation: Clin Infect Dis. 2005 Dec 1;41(11):1559-68
references.pmid: 16267727
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: FEMS Yeast Res. 2009 Aug;9(5):789-92
references.pmid: 19519766
references.citation: Mol Biol Evol. 2014 Apr;31(4):872-88
references.pmid: 24425782
references.citation: PLoS Genet. 2011 Jun;7(6):e1002111
references.pmid: 21698134
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12825-30
references.pmid: 17652520
references.citation: Mol Ecol. 2011 Oct;20(19):4085-97
references.pmid: 21880084
references.citation: J Mol Biol. 1981 Mar 25;147(1):195-7
references.pmid: 7265238
references.citation: Bioinformatics. 2007 Nov 1;23(21):2947-8
references.pmid: 17846036
references.citation: FEMS Yeast Res. 2002 Jan;1(4):299-306
references.pmid: 12702333
references.citation: PLoS One. 2011;6(9):e25211
references.pmid: 21966457
references.citation: Cell Host Microbe. 2012 Feb 16;11(2):106-15
references.pmid: 22341460
references.citation: J Infect Dis. 1994 Apr;169(4):859-67
references.pmid: 8133102
references.citation: Nat Genet. 2012 Jul;44(7):821-4
references.pmid: 22706312