Detection and analysis of alternative splicing in Yarrowia lipolytica reveal structural constraints facilitating nonsense-mediated decay of intron-retaining transcripts

Genome Biology

Volumn 11, Issue 6, 2010, Pages

  Mekouar, Meryem ^a   Blanc Lenfle, Isabelle ^a   Ozanne, Christophe ^a   Da Silva, Corinne ^b   Cruaud, Corinne ^b   Wincker, Patrick ^b   Gaillardin, Claude ^a   Neuvéglise, Cécile ^a  

^a UMR1319 MICALIS   (France)

^b CENTRE NATIONAL DE SÉQUENÇAGE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY DNA; MESSENGER RNA; NUCLEOTIDE; FUNGAL PROTEIN; FUNGAL RNA;

ALTERNATIVE RNA SPLICING; ARTICLE; CODON; DNA DEGRADATION; DNA SEQUENCE; FUNGAL DETECTION; FUNGAL GENE; GENE STRUCTURE; GENETIC IDENTIFICATION; GENETIC MODEL; GENETIC TRANSCRIPTION; INTRON; NONHUMAN; NUCLEOTIDE SEQUENCE; SACCHAROMYCES CEREVISIAE; SEQUENCE HOMOLOGY; STOP CODON; UNINDEXED SEQUENCE; UPF1 GENE; UPF2 GENE; UPF3 GENE; YARROWIA LIPOLYTICA; AMINO ACID SEQUENCE; BIOLOGICAL MODEL; CHEMISTRY; GENE EXPRESSION REGULATION; GENE LIBRARY; GENETICS; METABOLISM; MOLECULAR GENETICS; RNA STABILITY; YARROWIA;

SACCHAROMYCES CEREVISIAE; YARROWIA LIPOLYTICA;

ALTERNATIVE SPLICING; AMINO ACID SEQUENCE; BASE SEQUENCE; CODON, NONSENSE; DNA, COMPLEMENTARY; FUNGAL PROTEINS; GENE EXPRESSION REGULATION, FUNGAL; GENE LIBRARY; GENES, FUNGAL; INTRONS; MODELS, GENETIC; MOLECULAR SEQUENCE DATA; RNA STABILITY; RNA, FUNGAL; RNA, MESSENGER; SACCHAROMYCES CEREVISIAE; SEQUENCE ANALYSIS, DNA; YARROWIA;

EID: 77953727819     PISSN: 14747596     EISSN: 1474760X     Source Type: Journal    
DOI: 10.1186/gb-2010-11-6-r65     Document Type: Article

References (88)

1. Dujon B, Sherman D, Fischer G, Durrens P, Casaregola S, Lafontaine I, De Montigny J, Marck C, Neuvéglise C, Talla E, Goffard N, Frangeul L, Aigle M, Anthouard V, Babour A, Barbe V, Barnay S, Blanchin S, Beckerich JM, Beyne E, Bleykasten C, Boisramé A, Boyer J, Cattolico L, Confanioleri F, De Daruvar A, Despons L, Fabre E, Fairhead C, Ferry-Dumazet H, et al. Genome evolution in yeasts. Nature 2004, 430:35-44. 10.1038/nature02579, 15229592.
2. Souciet JL, Dujon B, Gaillardin C, Johnston M, Baret PV, Cliften P, Sherman DJ, Weissenbach J, Westhof E, Wincker P, Jubin C, Poulain J, Barbe V, Ségurens B, Artiguenave F, Anthouard V, Vacherie B, Val ME, Fulton RS, Minx P, Wilson R, Durrens P, Jean G, Marck C, Martin T, Nikolski M, Rolland T, Seret ML, Casarégola S, Despons L, et al. Comparative genomics of protoploid Saccharomycetaceae. Genome Res 2009, 19:1696-1709. 10.1101/gr.091546.109, 2765284, 19525356.
3. Dietrich FS, Voegeli S, Brachat S, Lerch A, Gates K, Steiner S, Mohr C, Pöhlmann R, Luedi P, Choi S, Wing RA, Flavier A, Gaffney TD, Philippsen P. The Ashbya gossypii genome as a tool for mapping the ancient Saccharomyces cerevisiae genome. Science 2004, 304:304-307. 10.1126/science.1095781, 15001715.
4. Vernis L, Poljak L, Chasles M, Uchida K, Casarégola S, Käs E, Matsuoka M, Gaillardin C, Fournier P. Only centromeres can supply the partition system required for ARS function in the yeast Yarrowia lipolytica. J Mol Biol 2001, 305:203-217. 10.1006/jmbi.2000.4300, 11124900.
5. Marck C, Kachouri-Lafond R, Lafontaine I, Westhof E, Dujon B, Grosjean H. The RNA polymerase III-dependent family of genes in hemiascomycetes: comparative RNomics, decoding strategies, transcription and evolutionary implications. Nucleic Acids Res 2006, 34:1816-1835. 10.1093/nar/gkl085, 1447645, 16600899.
6. Bergeron J, Drouin G. The evolution of 5S ribosomal RNA genes linked to the rDNA units of fungal species. Curr Genet 2008, 54:123-131. 10.1007/s00294-008-0201-2, 18704425.
7. Acker J, Ozanne C, Kachouri-Lafond R, Gaillardin C, Neuvéglise C, Marck C. Dicistronic tRNA-5S rRNA genes in Yarrowia lipolytica: an alternative TFIIIA-independent way for expression of 5S rRNA genes. Nucleic Acids Res 2008, 36:5832-5844. 10.1093/nar/gkn549, 2566860, 18790808.
8. Fournier P, Gaillardin C, Persuy MA, Klootwijk J, van Heerikhuizen H. Heterogeneity in the ribosomal family of the yeast Yarrowia lipolytica: genomic organization and segregation studies. Gene 1986, 42:273-282. 10.1016/0378-1119(86)90231-3, 3015740.
9. De Schutter K, Lin Y, Tiels P, Van Hecke A, Glinka S, Weber-Lehmann J, Rouzé P, Van de Peer Y, Callewaert N. Genome sequence of the recombinant protein production host Pichia pastoris. Nat Biotechnol 2009, 27:561-566. 10.1038/nbt.1544, 19465926.
10. Casaregola S, Neuvéglise C, Bon E, Gaillardin C. Ylli, a non-LTR retrotransposon L1 family in the dimorphic yeast Yarrowia lipolytica. Mol Biol Evol 2002, 19:664-677.
11. Kovalchuk A, Senam S, Mauersberger S, Barth G. Tyl6, a novel Ty3/gypsy-like retrotransposon in the genome of the dimorphic fungus Yarrowia lipolytica. Yeast 2005, 22:979-991. 10.1002/yea.1287, 16134118.
12. Neuvéglise C, Feldmann H, Bon E, Gaillardin C, Casaregola S. Genomic evolution of the long terminal repeat retrotransposons in hemiascomycetous yeasts. Genome Res 2002, 12:930-943. 10.1101/gr.219202, 1383729, 12045146.
13. Neuvéglise C, Chalvet F, Wincker P, Gaillardin C, Casaregola S. Mutator-like element in the yeast Yarrowia lipolytica displays multiple alternative splicings. Eukaryot Cell 2005, 4:615-624. 10.1128/EC.4.3.615-624.2005, 1087794, 15755923.
14. Bon E, Casaregola S, Blandin G, Llorente B, Neuvéglise C, Munsterkotter M, Guldener U, Mewes HW, Van Helden J, Dujon B, Gaillardin C. Molecular evolution of eukaryotic genomes: hemiascomycetous yeast spliceosomal introns. Nucleic Acids Res 2003, 31:1121-1135. 10.1093/nar/gkg213, 150231, 12582231.
15. Juneau K, Palm C, Miranda M, Davis RW. High-density yeast-tiling array reveals previously undiscovered introns and extensive regulation of meiotic splicing. Proc Natl Acad Sci USA 2007, 104:1522-1527. 10.1073/pnas.0610354104, 1780280, 17244705.
16. Mitrovich QM, Tuch BB, Guthrie C, Johnson AD. Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicans. Genome Res 2007, 17:492-502. 10.1101/gr.6111907, 1832096, 17351132.
17. Jeffares DC, Mourier T, Penny D. The biology of intron gain and loss. Trends Genet 2006, 22:16-22. 10.1016/j.tig.2005.10.006, 16290250.
18. Vanácová S, Yan W, Carlton JM, Johnson PJ. Spliceosomal introns in the deep-branching eukaryote Trichomonas vaginalis. Proc Natl Acad Sci USA 2005, 102:4430-4435. 10.1073/pnas.0407500102, 554003, 15764705.
19. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I. A genome annotation-driven approach to cloning the human ORFeome. Genome Biol 2004, 5:R84. 10.1186/gb-2004-5-10-r84, 545604, 15461802.
20. Stajich JE, Dietrich FS, Roy SW. Comparative genomic analysis of fungal genomes reveals intron-rich ancestors. Genome Biol 2007, 8:R223. 10.1186/gb-2007-8-10-r223, 2246297, 17949488.
21. Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, Armour CD, Santos R, Schadt EE, Stoughton R, Shoemaker DD. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science 2003, 302:2141-2144. 10.1126/science.1090100, 14684825.
22. Kim E, Magen A, Ast G. Different levels of alternative splicing among eukaryotes. Nucleic Acids Res 2007, 35:125-131. 10.1093/nar/gkl924, 1802581, 17158149.
23. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, et al. Initial sequencing and analysis of the human genome. Nature 2001, 409:860-921. 10.1038/35057062, 11237011.
24. Srebrow A, Kornblihtt AR. The connection between splicing and cancer. J Cell Sci 2006, 119:2635-2641. 10.1242/jcs.03053, 16787944.
25. Venables JP. Unbalanced alternative splicing and its significance in cancer. Bioessays 2006, 28:378-386. 10.1002/bies.20390, 16547952.
26. Habara Y, Urushiyama S, Tani T, Ohshima Y. The fission yeast prp10(+) gene involved in pre-mRNA splicing encodes a homologue of highly conserved splicing factor, SAP155. Nucleic Acids Res 1998, 26:5662-5669. 10.1093/nar/26.24.5662, 148038, 9837997.
27. Preker PJ, Kim KS, Guthrie C. Expression of the essential mRNA export factor Yra1p is autoregulated by a splicing-dependent mechanism. RNA 2002, 8:969-980. 10.1017/S1355838202020046, 1370319, 12212852.
28. Juneau K, Nislow C, Davis RW. Alternative splicing of PTC7 in Saccharomyces cerevisiae determines protein localization. Genetics 2009, 183:185-194. 10.1534/genetics.109.105155, 2746143, 19564484.
29. Davis CA, Grate L, Spingola M, Ares MJ. Test of intron predictions reveals novel splice sites, alternatively spliced mRNAs and new introns in meiotically regulated genes of yeast. Nucleic Acids Res 2000, 28:1700-1706. 10.1093/nar/28.8.1700, 102823, 10734188.
30. Rodríguez-Navarro S, Igual JC, Pérez-Ortín JE. SRC1: an intron-containing yeast gene involved in sister chromatid segregation. Yeast 2002, 19:43-54. 10.1002/yea.803, 11754482.
31. Miura F, Kawaguchi N, Sese J, Toyoda A, Hattori M, Morishita S, Ito T. A large-scale full-length cDNA analysis to explore the budding yeast transcriptome. Proc Natl Acad Sci USA 2006, 103:17846-17851. 10.1073/pnas.0605645103, 1693835, 17101987.
32. David L, Huber W, Granovskaia M, Toedling J, Palm CJ, Bofkin L, Jones T, Davis RW, Steinmetz LM. A high-resolution map of transcription in the yeast genome. Proc Natl Acad Sci USA 2006, 103:5320-5325. 10.1073/pnas.0601091103, 1414796, 16569694.
33. Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, Gerstein M, Snyder M. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 2008, 320:1344-1349. 10.1126/science.1158441, 2951732, 18451266.
34. Wilhelm BT, Marguerat S, Watt S, Schubert F, Wood V, Goodhead I, Penkett CJ, Rogers J, Bähler J. Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution. Nature 2008, 453:1239-1243. 10.1038/nature07002, 18488015.
35. Roy SW, Irimia M. Intron mis-splicing: no alternative?. Genome Biol 2008, 9:208. 10.1186/gb-2008-9-2-208, 2374719, 18304372.
36. Sayani S, Janis M, Lee CY, Toesca I, Chanfreau GF. Widespread impact of nonsense-mediated mRNA decay on the yeast intronome. Mol Cell 2008, 31:360-370. 10.1016/j.molcel.2008.07.005, 2600495, 18691968.
37. Pleiss JA, Whitworth GB, Bergkessel M, Guthrie C. Rapid, transcript-specific changes in splicing in response to environmental stress. Mol Cell 2007, 27:928-937. 10.1016/j.molcel.2007.07.018, 2081968, 17889666.
38. Engebrecht JA, Voelkel-Meiman K, Roeder GS. Meiosis-specific RNA splicing in yeast. Cell 1991, 66:1257-1268. 10.1016/0092-8674(91)90047-3, 1840507.
39. Nakagawa T, Ogawa H. The Saccharomyces cerevisiae MER3 gene, encoding a novel helicase-like protein, is required for crossover control in meiosis. EMBO J 1999, 18:5714-5723. 10.1093/emboj/18.20.5714, 1171638, 10523314.
40. Vilardell J, Chartrand P, Singer RH, Warner JR. The odyssey of a regulated transcript. RNA 2000, 6:1773-1780. 10.1017/S135583820000145X, 1370047, 11142377.
41. Preker PJ, Guthrie C. Autoregulation of the mRNA export factor Yra1p requires inefficient splicing of its pre-mRNA. RNA 2006, 12:994-1006. 10.1261/rna.6706, 1464842, 16618971.
42. Dong S, Li C, Zenklusen D, Singer RH, Jacobson A, He F. YRA1 autoregulation requires nuclear export and cytoplasmic Edc3p-mediated degradation of its pre-mRNA. Mol Cell 2007, 25:559-573. 10.1016/j.molcel.2007.01.012, 1858660, 17317628.
43. Behm-Ansmant I, Kashima I, Rehwinkel J, Saulière J, Wittkopp N, Izaurralde E. mRNA quality control: an ancient machinery recognizes and degrades mRNAs with nonsense codons. FEBS Lett 2007, 581:2845-2853. 10.1016/j.febslet.2007.05.027, 17531985.
44. Rehwinkel J, Raes J, Izaurralde E. Nonsense-mediated mRNA decay: Target genes and functional diversification of effectors. Trends Biochem Sci 2006, 31:639-646. 10.1016/j.tibs.2006.09.005, 17010613.
45. Stalder L, Mühlemann O. The meaning of nonsense. Trends Cell Biol 2008, 18:315-321. 10.1016/j.tcb.2008.04.005, 18524595.
46. Kertész S, Kerényi Z, Mérai Z, Bartos I, Pálfy T, Barta E, Silhavy D. Both introns and long 3'-UTRs operate as cis-acting elements to trigger nonsense-mediated decay in plants. Nucleic Acids Res 2006, 34:6147-6157. 10.1093/nar/gkl737, 1693880, 17088291.
47. Kerényi Z, Mérai Z, Hiripi L, Benkovics A, Gyula P, Lacomme C, Barta E, Nagy F, Silhavy D. Inter-kingdom conservation of mechanism of nonsense-mediated mRNA decay. EMBO J 2008, 27:1585-1595. 10.1038/emboj.2008.88, 2426726, 18451801.
48. Amrani N, Ganesan R, Kervestin S, Mangus DA, Ghosh S, Jacobson A. A faux 3'-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay. Nature 2004, 432:112-118. 10.1038/nature03060, 15525991.
49. Mühlemann O, Eberle AB, Stalder L, Zamudio Orozco R. Recognition and elimination of nonsense mRNA. Biochim Biophys Acta 2008, 1779:538-549.
50. Jaillon O, Bouhouche K, Gout JF, Aury JM, Noel B, Saudemont B, Nowacki M, Serrano V, Porcel BM, Ségurens B, Le Mouël A, Lepère G, Schächter V, Bétermier M, Cohen J, Wincker P, Sperling L, Duret L, Meyer E. Translational control of intron splicing in eukaryotes. Nature 2008, 451:359-362. 10.1038/nature06495, 18202663.
51. Desfougères T, Haddouche R, Fudalej F, Neuvéglise C, Nicaud J. SOA genes encode proteins controlling lipase expression in response to triacylglycerol utilization in the yeast Yarrowia lipolytica. FEMS Yeast Res 2009, 10:93-103. 10.1111/j.1567-1364.2009.00590.x, 19922427.
52. Génolevures Database. , http://www.genolevures.org/yali.html
53. Kupfer DM, Drabenstot SD, Buchanan KL, Lai H, Zhu H, Dyer DW, Roe BA, Murphy JW. Introns and splicing elements of five diverse fungi. Eukaryot Cell 2004, 3:1088-1100. 10.1128/EC.3.5.1088-1100.2004, 522613, 15470237.
54. Spingola M, Grate L, Haussler D, Ares MJ. Genome-wide bioinformatic and molecular analysis of introns in Saccharomyces cerevisiae. RNA 1999, 5:221-234. 10.1017/S1355838299981682, 1369754, 10024174.
55. Lin K, Zhang D. The excess of 5' introns in eukaryotic genomes. Nucleic Acids Res 2005, 33:6522-6527. 10.1093/nar/gki970, 1292992, 16314314.
56. Mourier T, Jeffares DC. Eukaryotic intron loss. Science 2003, 300:1393. 10.1126/science.1080559, 12775832.
57. Hong X, Scofield DG, Lynch M. Intron size, abundance, and distribution within untranslated regions of genes. Mol Biol Evol 2006, 23:2392-2404. 10.1093/molbev/msl111, 16980575.
58. Schwartz SH, Silva J, Burstein D, Pupko T, Eyras E, Ast G. Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes. Genome Res 2008, 18:88-103. 10.1101/gr.6818908, 2134773, 18032728.
59. Irimia M, Roy SW. Evolutionary convergence on highly-conserved 3' intron structures in intron-poor eukaryotes and insights into the ancestral eukaryotic genome. PLoS Genet 2008, 4:e1000148. 10.1371/journal.pgen.1000148, 2483917, 18688272.
60. Irimia M, Penny D, Roy SW. Coevolution of genomic intron number and splice sites. Trends Genet 2007, 23:321-325. 10.1016/j.tig.2007.04.001, 17442445.
61. Lopez PJ, Séraphin B. Genomic-scale quantitative analysis of yeast pre-mRNA splicing: implications for splice-site recognition. RNA 1999, 5:1135-1137. 10.1017/S135583829999091X, 1369835, 10496213.
62. Génosplicing. , http://genome.jouy.inra.fr/genosplicing/index.html
63. Fedorov A, Suboch G, Bujakov M, Fedorova L. Analysis of nonuniformity in intron phase distribution. Nucleic Acids Res 1992, 20:2553-2557. 10.1093/nar/20.10.2553, 312392, 1598214.
64. Ruvinsky A, Eskesen ST, Eskesen FN, Hurst LD. Can codon usage bias explain intron phase distributions and exon symmetry?. J Mol Evol 2005, 60:99-104. 10.1007/s00239-004-0032-9, 15696372.
65. Long M, de Souza SJ, Rosenberg C, Gilbert W. Relationship between "proto-splice sites" and intron phases: evidence from dicodon analysis. Proc Natl Acad Sci USA 1998, 95:219-223. 10.1073/pnas.95.1.219, 18181, 9419356.
66. Whamond GS, Thornton JM. An analysis of intron positions in relation to nucleotides, amino acids, and protein secondary structure. J Mol Biol 2006, 359:238-247. 10.1016/j.jmb.2006.03.029, 16616935.
67. Long M, de Souza SJ, Gilbert W. The yeast splice site revisited: new exon consensus from genomic analysis. Cell 1997, 91:739-740. 10.1016/S0092-8674(00)80462-6, 9413983.
68. Leeds P, Wood JM, Lee BS, Culbertson MR. Gene products that promote mRNA turnover in Saccharomyces cerevisiae. Mol Cell Biol 1992, 12:2165-2177. 364388, 1569946.
69. Cui Y, Hagan KW, Zhang S, Peltz SW. Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon. Genes Dev 1995, 9:423-436. 10.1101/gad.9.4.423, 7883167.
70. Howe KJ, Kane CM, Ares MJ. Perturbation of transcription elongation influences the fidelity of internal exon inclusion in Saccharomyces cerevisiae. RNA 2003, 9:993-1006. 10.1261/rna.5390803, 1370465, 12869710.
71. Romfo CM, Alvarez CJ, van Heeckeren WJ, Webb CJ, Wise JA. Evidence for splice site pairing via intron definition in Schizosaccharomyces pombe. Mol Cell Biol 2000, 20:7955-7970. 10.1128/MCB.20.21.7955-7970.2000, 86406, 11027266.
72. McGuire AM, Pearson MD, Neafsey DE, Galagan JE. Cross-kingdom patterns of alternative splicing and splice recognition. Genome Biol 2008, 9:R50. 10.1186/gb-2008-9-3-r50, 2397502, 18321378.
73. Loftus BJ, Fung E, Roncaglia P, Rowley D, Amedeo P, Bruno D, Vamathevan J, Miranda M, Anderson IJ, Fraser JA, Allen JE, Bosdet IE, Brent MR, Chiu R, Doering TL, Donlin MJ, D'Souza CA, Fox DS, Grinberg V, Fu J, Fukushima M, Haas BJ, Huang JC, Janbon G, Jones SJ, Koo HL, Krzywinski MI, Kwon-Chung JK, Lengeler KB, Maiti R, et al. The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science 2005, 307:1321-1324. 10.1126/science.1103773, 15653466.
74. Ebbole DJ, Jin Y, Thon M, Pan H, Bhattarai E, Thomas T, Dean R. Gene discovery and gene expression in the rice blast fungus, Magnaporthe grisea: analysis of expressed sequence tags. Mol Plant Microbe Interact 2004, 17:1337-1347. 10.1094/MPMI.2004.17.12.1337, 15597739.
75. Galagan JE, Henn MR, Ma L, Cuomo CA, Birren B. Genomics of the fungal kingdom: insights into eukaryotic biology. Genome Res 2005, 15:1620-1631. 10.1101/gr.3767105, 16339359.
76. Goguel V, Rosbash M. Splice site choice and splicing efficiency are positively influenced by pre-mRNA intramolecular base pairing in yeast. Cell 1993, 72:893-901. 10.1016/0092-8674(93)90578-E, 8458083.
77. Rogic S, Montpetit B, Hoos HH, Mackworth AK, Ouellette BF, Hieter P. Correlation between the secondary structure of pre-mRNA introns and the efficiency of splicing in Saccharomyces cerevisiae. BMC Genomics 2008, 9:355. 10.1186/1471-2164-9-355, 2536676, 18664289.
78. Görnemann J, Kotovic KM, Hujer K, Neugebauer KM. Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the cap binding complex. Mol Cell 2005, 19:53-63. 10.1016/j.molcel.2005.05.007, 15989964.
79. Kornblihtt AR, de la Mata M, Fededa JP, Munoz MJ, Nogues G. Multiple links between transcription and splicing. RNA 2004, 10:1489-1498. 10.1261/rna.7100104, 1370635, 15383674.
80. Kornblihtt AR. Promoter usage and alternative splicing. Curr Opin Cell Biol 2005, 17:262-268. 10.1016/j.ceb.2005.04.014, 15901495.
81. ImageJ. , http://rsbweb.nih.gov/ij/index.html
82. Zimmermann M, Fournier P. Electrophoretic karyotyping of yeasts. Nonconventional Yeasts in Biotechnology 1996, 101-116. Berlin, Germany: Springer-Verlag, Wolf K.
83. Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: a Laboratory Manual 1989, Cold Spring Harbor NY: Cold Spring Harbor Laboratory Press, 2.
84. Fickers P, Le Dall MT, Gaillardin C, Thonart P, Nicaud JM. New disruption cassettes for rapid gene disruption and marker rescue in the yeast Yarrowia lipolytica. J Microbiol Methods 2003, 55:727-737. 10.1016/j.mimet.2003.07.003, 14607415.
85. Le Dall MT, Nicaud JM, Gaillardin C. Multiple-copy integration in the yeast Yarrowia lipolytica. Curr Genet 1994, 26:38-44. 10.1007/BF00326302, 7954894.
86. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990, 215:403-410.
87. Crooks GE, Hon G, Chandonia J, Brenner SE. WebLogo: a sequence logo generator. Genome Res 2004, 14:1188-1190. 10.1101/gr.849004, 419797, 15173120.
88. Schneider TD, Stephens RM. Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 1990, 18:6097-6100. 10.1093/nar/18.20.6097, 332411, 2172928.