A global view of pleiotropy and phenotypically derived gene function in yeast

被引:230
作者
Dudley, Aimee Marie
Janse, Daniel Maarten
Tanay, Amos
Shamir, Ron
Church, George McDonald
机构
[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[2] Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel
关键词
bicluster; genetics; genomics; phenotype; yeast deletion;
D O I
10.1038/msb4100004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pleiotropy, the ability of a single mutant gene to cause multiple mutant phenotypes, is a relatively common but poorly understood phenomenon in biology. Perhaps the greatest challenge in the analysis of pleiotropic genes is determining whether phenotypes associated with a mutation result from the loss of a single function or of multiple functions encoded by the same gene. Here we estimate the degree of pleiotropy in yeast by measuring the phenotypes of 4710 mutants under 21 environmental conditions, finding that it is significantly higher than predicted by chance. We use a biclustering algorithm to group pleiotropic genes by common phenotype profiles. Comparisons of these clusters to biological process classifications, synthetic lethal interactions, and protein complex data support the hypothesis that this method can be used to genetically define cellular functions. Applying these functional classifications to pleiotropic genes, we are able to dissect phenotypes into groups associated with specific gene functions.
引用
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页数:11
相关论文
共 47 条
[31]   Two steps forward, one step back: the pleiotropic effects of favoured alleles [J].
Otto, SP .
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2004, 271 (1540) :705-714
[32]   Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways [J].
Parsons, AB ;
Brost, RL ;
Ding, HM ;
Li, ZJ ;
Zhang, CY ;
Sheikh, B ;
Brown, GW ;
Kane, PM ;
Hughes, TR ;
Boone, C .
NATURE BIOTECHNOLOGY, 2004, 22 (01) :62-69
[33]  
Roberts SM, 1997, GENETICS, V147, P451
[34]  
Rose MD, 1990, Methods in Yeast Genetics: A Laboratory Course Manual
[35]   Systematic variation in gene expression patterns in human cancer cell lines [J].
Ross, DT ;
Scherf, U ;
Eisen, MB ;
Perou, CM ;
Rees, C ;
Spellman, P ;
Iyer, V ;
Jeffrey, SS ;
Van de Rijn, M ;
Waltham, M ;
Pergamenschikov, A ;
Lee, JCE ;
Lashkari, D ;
Shalon, D ;
Myers, TG ;
Weinstein, JN ;
Botstein, D ;
Brown, PO .
NATURE GENETICS, 2000, 24 (03) :227-235
[36]   β-subunits of Snf1 kinase are required for kinase function and substrate definition [J].
Schmidt, MC ;
McCartney, RR .
EMBO JOURNAL, 2000, 19 (18) :4936-4943
[37]   siRNA technology [J].
Schütze, N .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2004, 213 (02) :115-119
[38]   A module map showing conditional activity of expression modules in cancer [J].
Segal, E ;
Friedman, N ;
Koller, D ;
Regev, A .
NATURE GENETICS, 2004, 36 (10) :1090-1098
[39]  
SEGAL E, 2001, BIOINFORMATICS S1, V17, P243, DOI DOI 10.1093/BIOINFORMATICS/17.SUPPL_1.S243
[40]  
Sokal RR., 1995, BIOMETRY PRINCIPLES