Transcription control reprogramming in genetic backup circuits

被引:147
作者
Kafri, R [1 ]
Bar-Even, A [1 ]
Pilpel, Y [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
关键词
D O I
10.1038/ng1523
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
A key question in molecular genetics is why severe mutations often do not result in a detectably abnormal phenotype. This robustness was partially ascribed to redundant paralogs(1,2) that may provide backup for one another in case of mutation. Mining mutant viability and mRNA expression data in Saccharomyces cerevisiae, we found that backup was provided predominantly by paralogs that are expressed dissimilarly in most growth conditions. We considered that this apparent inconsistency might be resolved by a transcriptional reprogramming mechanism that allows the intact paralog to rescue the organism upon mutation of its counterpart. We found that in wild-type cells, partial coregulation across growth conditions predicted the ability of paralogs to alter their transcription patterns and to provide backup for one another. Notably, the sets of regulatory motifs that controlled the paralogs with the most efficient backup activity deliberately overlapped only partially; paralogs with highly similar or dissimilar sets of motifs had suboptimal backup activity. Such an arrangement of partially shared regulatory motifs reconciles the differential expression of paralogs with their ability to back each other up.
引用
收藏
页码:295 / 299
页数:5
相关论文
共 30 条
[1]   Patterns of gene duplication in Saccharomyces cerevisiae and Caenorhabditis elegans [J].
Cavalcanti, ARO ;
Ferreira, R ;
Gu, ZL ;
Li, WH .
JOURNAL OF MOLECULAR EVOLUTION, 2003, 56 (01) :28-37
[2]   Duplicate genes and robustness to transient gene knock-downs in Caenorhabditis elegans [J].
Conant, GC ;
Wagner, A .
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2004, 271 (1534) :89-96
[3]  
Force A, 1999, GENETICS, V151, P1531
[4]   Characterization of the chitin biosynthesis process as a compensatory mechanism in the fks1 mutant of Saccharomyces cerevisiae [J].
García-Rodriguez, LJ ;
Trilla, JA ;
Castro, C ;
Valdivieso, MH ;
Durán, A ;
Roncero, C .
FEBS LETTERS, 2000, 478 (1-2) :84-88
[5]   Correlation between transcriptome and interactome mapping data from Saccharomyces cerevisiae [J].
Ge, H ;
Liu, ZH ;
Church, GM ;
Vidal, M .
NATURE GENETICS, 2001, 29 (04) :482-486
[6]  
GOLDMAN N, 1994, MOL BIOL EVOL, V11, P725
[7]   Role of duplicate genes in genetic robustness against null mutations [J].
Gu, ZL ;
Steinmetz, LM ;
Gu, X ;
Scharfe, C ;
Davis, RW ;
Li, WH .
NATURE, 2003, 421 (6918) :63-66
[8]   Rapid divergence in expression between duplicate genes inferred from microarray data [J].
Gu, ZL ;
Nicolae, D ;
Lu, HHS ;
Li, WH .
TRENDS IN GENETICS, 2002, 18 (12) :609-613
[9]   Transcriptional regulatory code of a eukaryotic genome [J].
Harbison, CT ;
Gordon, DB ;
Lee, TI ;
Rinaldi, NJ ;
Macisaac, KD ;
Danford, TW ;
Hannett, NM ;
Tagne, JB ;
Reynolds, DB ;
Yoo, J ;
Jennings, EG ;
Zeitlinger, J ;
Pokholok, DK ;
Kellis, M ;
Rolfe, PA ;
Takusagawa, KT ;
Lander, ES ;
Gifford, DK ;
Fraenkel, E ;
Young, RA .
NATURE, 2004, 431 (7004) :99-104
[10]   Functional discovery via a compendium of expression profiles [J].
Hughes, TR ;
Marton, MJ ;
Jones, AR ;
Roberts, CJ ;
Stoughton, R ;
Armour, CD ;
Bennett, HA ;
Coffey, E ;
Dai, HY ;
He, YDD ;
Kidd, MJ ;
King, AM ;
Meyer, MR ;
Slade, D ;
Lum, PY ;
Stepaniants, SB ;
Shoemaker, DD ;
Gachotte, D ;
Chakraburtty, K ;
Simon, J ;
Bard, M ;
Friend, SH .
CELL, 2000, 102 (01) :109-126