title: Aneuploid chromosomes are highly unstable during DNA transformation of Candida albicans.
abstract: Candida albicans strains tolerate aneuploidy, historically detected as karyotype alterations by pulsed-field gel electrophoresis and more recently revealed by array comparative genome hybridization, which provides a comprehensive and detailed description of gene copy number. Here, we first retrospectively analyzed 411 expression array experiments to predict the frequency of aneuploidy in different strains. As expected, significant levels of aneuploidy were seen in strains exposed to stress conditions, including UV light and/or sorbose treatment, as well as in strains that are resistant to antifungal drugs. More surprisingly, strains that underwent transformation with DNA displayed the highest frequency of chromosome copy number changes, with strains that were initially aneuploid exhibiting approximately 3-fold more copy number changes than strains that were initially diploid. We then prospectively analyzed the effect of lithium acetate (LiOAc) transformation protocols on the stability of trisomic chromosomes. Consistent with the retrospective analysis, the proportion of karyotype changes was highly elevated in strains carrying aneuploid chromosomes. We then tested the hypothesis that stresses conferred by heat and/or LiOAc exposure promote chromosome number changes during DNA transformation procedures. Indeed, a short pulse of very high temperature caused frequent gains and losses of multiple chromosomes or chromosome segments. Furthermore, milder heat exposure over longer periods caused increased levels of loss of heterozygosity. Nonetheless, aneuploid chromosomes were also unstable when strains were transformed by electroporation, which does not include a heat shock step. Thus, aneuploid strains are particularly prone to undergo changes in chromosome number during the stresses of DNA transformation protocols.
authors.affiliation: University of Minnesota, GCD, 6-160 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Bouchonville
authors.forename: Anja
authors.initials: A
authors.lastname: Forche
authors.forename: Karen E S
authors.initials: KE
authors.lastname: Tang
authors.forename: Anna
authors.initials: A
authors.lastname: Selmecki
authors.forename: Judith
authors.initials: J
authors.lastname: Berman
mesh_terms: D000782:Aneuploidy; D002176:Candida albicans / Q000235:genetics*; D015825:Chromosomes, Fungal / Q000235:genetics*; D004271:DNA, Fungal / Q000737:chemistry*; D016681:Genome, Fungal; D019656:Loss of Heterozygosity; D020411:Oligonucleotide Array Sequence Analysis; D014170:Transformation, Genetic
chemical_list: D004271:DNA, Fungal
references.citation: Cell Oncol. 2005;27(5-6):293-318
references.pmid: 16373963
references.citation: Eukaryot Cell. 2005 Jul;4(7):1203-10
references.pmid: 16002646
references.citation: Microbiol Rev. 1990 Sep;54(3):226-41
references.pmid: 2215421
references.citation: Res Microbiol. 2005 Nov;156(9):911-20
references.pmid: 16024227
references.citation: Curr Genet. 1992 Aug;22(2):93-100
references.pmid: 1423721
references.citation: FEMS Yeast Res. 2009 Oct;9(7):1061-9
references.pmid: 19622074
references.citation: PLoS Biol. 2008 May 6;6(5):e110
references.pmid: 18462019
references.citation: Cell Cycle. 2003 May-Jun;2(3):202-10
references.pmid: 12734426
references.citation: Yeast. 2008 Jun;25(6):433-48
references.pmid: 18509849
references.citation: Fungal Genet Biol. 2006 Feb;43(2):124-34
references.pmid: 16455273
references.citation: Mol Microbiol. 2005 Apr;56(2):397-415
references.pmid: 15813733
references.citation: Sci Am. 2007 May;296(5):52-9
references.pmid: 17500414
references.citation: Mol Biol Cell. 2003 Apr;14(4):1460-7
references.pmid: 12686601
references.citation: J Antimicrob Chemother. 2005 May;55(5):655-62
references.pmid: 15814599
references.citation: Bioinformatics. 2008 Jul 1;24(13):1559-61
references.pmid: 18499696
references.citation: Antimicrob Agents Chemother. 2006 Jul;50(7):2384-94
references.pmid: 16801416
references.citation: Mol Biol Cell. 2005 Jun;16(6):2903-12
references.pmid: 15814840
references.citation: Mol Microbiol. 2005 Mar;55(5):1553-65
references.pmid: 15720560
references.citation: Mol Biol Cell. 2006 Jan;17(1):295-307
references.pmid: 16267276
references.citation: Eukaryot Cell. 2004 Dec;3(6):1639-52
references.pmid: 15590837
references.citation: Mol Microbiol. 2008 May;68(3):624-41
references.pmid: 18363649
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9284-9
references.pmid: 12089321
references.citation: J Antimicrob Chemother. 2005 May;55(5):645-54
references.pmid: 15820985
references.citation: Eukaryot Cell. 2004 Oct;3(5):1076-87
references.pmid: 15470236
references.citation: Science. 2006 Jul 21;313(5785):367-70
references.pmid: 16857942
references.citation: J Bacteriol. 1999 Jul;181(13):4041-9
references.pmid: 10383973
references.citation: PLoS Biol. 2009 Jul;7(7):e1000161
references.pmid: 19636358
references.citation: J Med Vet Mycol. 1995 Nov-Dec;33(6):361-6
references.pmid: 8683403
references.citation: Eukaryot Cell. 2005 Oct;4(10):1687-96
references.pmid: 16215176
references.citation: Eukaryot Cell. 2004 Oct;3(5):1111-23
references.pmid: 15470239
references.citation: Genetics. 1993 Jul;134(3):717-28
references.pmid: 8349105
references.citation: Mol Biol Cell. 2004 Oct;15(10):4490-9
references.pmid: 15269278
references.citation: Mol Microbiol. 2006 Mar;59(5):1429-51
references.pmid: 16468987
references.citation: Mol Biol Cell. 2002 Oct;13(10):3452-65
references.pmid: 12388749
references.citation: Mol Microbiol. 2006 Oct;62(1):100-19
references.pmid: 16987174
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5150-5
references.pmid: 9560244
references.citation: J Bacteriol. 1997 Apr;179(7):2331-8
references.pmid: 9079920
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):5048-52
references.pmid: 15051880
references.citation: Nature. 2006 Sep 28;443(7110):415-20
references.pmid: 17006507
references.citation: Mol Biol Cell. 2005 Jun;16(6):2913-25
references.pmid: 15814841
references.citation: J Infect Dis. 2005 Sep 1;192(5):893-900
references.pmid: 16088840
references.citation: J Genet. 1949 Dec;49(3):264-85
references.pmid: 24536673
references.citation: Science. 1999 Aug 20;285(5431):1271-5
references.pmid: 10455055
references.citation: Mol Microbiol. 2007 Mar;63(6):1606-28
references.pmid: 17367383
references.citation: Biochem Biophys Res Commun. 2005 Sep 9;334(4):1149-58
references.pmid: 16039996
references.citation: Methods Mol Biol. 2004;262:3-12
references.pmid: 14769952
references.citation: Science. 2005 Aug 5;309(5736):938-40
references.pmid: 16081737
references.citation: Nat Genet. 2000 Jul;25(3):333-7
references.pmid: 10888885
references.citation: Free Radic Biol Med. 2006 Apr 1;40(7):1201-9
references.pmid: 16545688
references.citation: Mol Biol Cell. 2004 Jul;15(7):3167-80
references.pmid: 15218092
references.citation: Mol Microbiol. 2004 Jun;52(5):1451-62
references.pmid: 15165246
references.citation: Eukaryot Cell. 2006 Aug;5(8):1252-65
references.pmid: 16896210
references.citation: Eukaryot Cell. 2004 Jun;3(3):705-14
references.pmid: 15189991
references.citation: Cell. 2003 Nov 14;115(4):389-99
references.pmid: 14622594
references.citation: Cell. 2008 Nov 28;135(5):879-93
references.pmid: 19041751
references.citation: Mol Microbiol. 2004 Feb;51(3):691-709
references.pmid: 14731272
references.citation: Science. 2000 Jul 14;289(5477):310-3
references.pmid: 10894781
references.citation: Eukaryot Cell. 2005 Jan;4(1):156-65
references.pmid: 15643071
references.citation: Bioinformatics. 2007 Oct 15;23(20):2700-7
references.pmid: 17720982
references.citation: Eukaryot Cell. 2006 Jan;5(1):180-91
references.pmid: 16400181
references.citation: Anticancer Res. 1999 Nov-Dec;19(6A):4887-906
references.pmid: 10697602
references.citation: Curr Opin Genet Dev. 2007 Apr;17(2):157-62
references.pmid: 17324569
references.citation: Clin Infect Dis. 1994 Feb;18(2):240-2
references.pmid: 8161633
references.citation: Mol Microbiol. 2004 Jan;51(2):551-65
references.pmid: 14756793
references.citation: Genome Biol. 2007;8(4):R52
references.pmid: 17419877
references.citation: PLoS Genet. 2008 Dec;4(12):e1000303
references.pmid: 19079573
references.citation: Antimicrob Agents Chemother. 2003 Apr;47(4):1220-7
references.pmid: 12654650
references.citation: Yeast. 2009 Jul;26(7):399-406
references.pmid: 19504625
references.citation: Curr Biol. 2005 Jun 21;15(12):1150-5
references.pmid: 15964282
references.citation: EMBO J. 2003 May 15;22(10):2505-15
references.pmid: 12743044
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12147-52
references.pmid: 16099828
references.citation: J Antimicrob Chemother. 2005 May;55(5):663-73
references.pmid: 15790671
references.citation: Eukaryot Cell. 2005 Jul;4(7):1175-90
references.pmid: 16002644
references.citation: Mol Microbiol. 2005 Aug;57(4):942-59
references.pmid: 16091036
references.citation: Curr Opin Genet Dev. 2009 Feb;19(1):74-81
references.pmid: 19195877
references.citation: Genetics. 2009 Jul;182(3):799-811
references.pmid: 19414562
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12807-12
references.pmid: 16899543
references.citation: Mol Biol Cell. 2006 Feb;17(2):1018-32
references.pmid: 16339080
references.citation: Fungal Genet Biol. 2007 Aug;44(8):789-98
references.pmid: 17300968
references.citation: Mol Gen Genet. 1985;200(1):162-8
references.pmid: 3897792
references.citation: Yeast. 2001 Jun 30;18(9):859-64
references.pmid: 11427968
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11007-12
references.pmid: 12958213
references.citation: Eukaryot Cell. 2006 Jan;5(1):192-202
references.pmid: 16400182
references.citation: Mol Biol Cell. 2005 Oct;16(10):4814-26
references.pmid: 16030247
references.citation: FEMS Yeast Res. 2007 Jan;7(1):2-11
references.pmid: 17311580
references.citation: J Mol Biol. 2006 Aug 18;361(3):399-411
references.pmid: 16854431
references.citation: Genetics. 2008 Jun;179(2):737-46
references.pmid: 18558649
references.citation: Science. 2007 Aug 17;317(5840):916-24
references.pmid: 17702937
references.citation: PLoS Pathog. 2006 Mar;2(3):e21
references.pmid: 16552442
references.citation: Bioinformatics. 2003 Jan 22;19(2):185-93
references.pmid: 12538238
references.citation: J Bacteriol. 1999 Mar;181(6):1868-74
references.pmid: 10074081
references.citation: Mol Microbiol. 2004 Dec;54(5):1335-51
references.pmid: 15554973
references.citation: PLoS Genet. 2008 Jan;4(1):e1
references.pmid: 18179283
references.citation: Antimicrob Agents Chemother. 2004 Aug;48(8):3064-79
references.pmid: 15273122
references.citation: Mol Gen Genet. 1982;187(3):477-85
references.pmid: 6757662
references.citation: J Bacteriol. 1994 Jul;176(13):3851-8
references.pmid: 8021166
references.citation: Methods. 2003 Dec;31(4):265-73
references.pmid: 14597310
references.citation: Gene. 2000 Jan 25;242(1-2):393-8
references.pmid: 10721733
references.citation: Mol Gen Genet. 1980;180(1):107-13
references.pmid: 7003306
references.citation: Yeast. 2005 Sep;22(12):957-69
references.pmid: 16134116
references.citation: Mol Microbiol. 2005 Apr;56(2):559-73
references.pmid: 15813744
references.citation: Yeast. 2004 Apr 15;21(5):429-36
references.pmid: 15116343