Transcriptional robustness and protein interactions are associated in yeast

BMC Systems Biology

Gavin C Conant¹  Michaël Bekaert² 

[1] Informatics Institute, University of Missouri, 920 East Campus Drive, Columbia, MO 65211, USA;Division of Animal Sciences, University of Missouri, 920 East Campus Drive, Columbia, MO 65211, USA

关键词: Saccharomyces cerevisiae;    Protein-Protein Interactions;    Epistasis;    Dosage balance;    Aneuploidy;   

Others  :  1160506
DOI  :  10.1186/1752-0509-5-62

 received in 2011-01-31, accepted in 2011-05-05,  发布年份 2011

【 摘 要 】

Background

Robustness to insults, both external and internal, is a characteristic feature of life. One level of biological organization for which noise and robustness have been extensively studied is gene expression. Cells have a variety of mechanisms for buffering noise in gene expression, but it is not completely clear what rules govern whether or not a given gene uses such tools to maintain appropriate expression.

Results

Here, we show a general association between the degree to which yeast cells have evolved mechanisms to buffer changes in gene expression and whether they possess protein-protein interactions. We argue that this effect bears an affinity to epistasis, because yeast appears to have evolved regulatory mechanisms such that distant changes in gene copy number for a protein-protein interaction partner gene can alter a gene's expression. This association is not unexpected given recent work linking epistasis and the deleterious effects of changes in gene dosage (i.e., the dosage balance hypothesis). Using gene expression data from artificial aneuploid strains of bakers' yeast, we found that genes coding for proteins that physically interact with other proteins show less expression variation in response to aneuploidy than do other genes. This effect is even more pronounced for genes whose products interact with proteins encoded on aneuploid chromosomes. We further found that genes targeted by transcription factors encoded on aneuploid chromosomes were more likely to change in expression after aneuploidy.

Conclusions

We suggest that these observations can be best understood as resulting from the higher fitness cost of misexpression in epistatic genes and a commensurate greater regulatory control of them.

【 授权许可】

   
2011 Bekaert and Conant; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Stelling J, Sauer U, Szallasi Z, Doyle FJ, Doyle J: Robustness of cellular functions. Cell 2004, 118(6):675-685.
• [2]Wagner A: Robustness and evolvability in living systems. Princeton, N.J.: Princeton University Press; 2005.
• [3]Raser JM, O'Shea EK: Noise in gene expression: origins, consequences, and control. Science 2005, 309(5743):2010-2013.
• [4]Becskei A, Serrano L: Engineering stability in gene networks by autoregulation. Nature 2000, 405(6786):590-593.
• [5]Cheng P, Yang Y, Liu Y: Interlocked feedback loops contribute to the robustness of the Neurospora circadian clock. Proc Natl Acad Sci USA 2001, 98(13):7408-7413.
• [6]Shen-Orr SS, Milo R, Mangan S, Alon U: Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 2002, 31(1):64-68.
• [7]Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U: Network motifs: simple building blocks of complex networks. Science 2002, 298(5594):824-827.
• [8]Klemm K, Bornholdt S: Topology of biological networks and reliability of information processing. Proc Natl Acad Sci USA 2005, 102(51):18414-18419.
• [9]Prill RJ, Iglesias PA, Levchenko A: Dynamic properties of network motifs contribute to biological network organization. PLoS Biol 2005, 3(11):e343.
• [10]Mangan S, Alon U: Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci USA 2003, 100(21):11980-11985.
• [11]von Dassow G, Meir E, Munro EM, Odell GM: The segment polarity network is a robust developmental module. Nature 2000, 406(6792):188-192.
• [12]Li F, Long T, Lu Y, Ouyang Q, Tang C: The yeast cell-cycle network is robustly designed. Proc Natl Acad Sci USA 2004, 101(14):4781-4786.
• [13]Steinmetz LM, Scharfe C, Deutschbauer AM, Mokranjac D, Herman ZS, Jones T, Chu AM, Giaever G, Prokisch H, Oefner PJ, Davis RW: Systematic screen for human disease genes in yeast. Nat Genet 2002, 31(4):400-404.
• [14]Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, Kanapin A, Le Bot N, Moreno S, Sohrmann M, Welchman DP, Zipperlen P, Ahringer J: Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 2003, 421(6920):231-237.
• [15]Gu Z, Steinmetz LM, Gu X, Scharfe C, Davis RW, Li WH: Role of duplicate genes in genetic robustness against null mutations. Nature 2003, 421(6918):63-66.
• [16]Phillips PC: Epistasis--the essential role of gene interactions in the structure and evolution of genetic systems. Nature Reviews Genetics 2008, 9(11):855-867.
• [17]Dean EJ, Davis JC, Davis RW, Petrov DA: Pervasive and persistent redundancy among duplicated genes in yeast. PLoS Genet 2008, 4(7):e1000113.
• [18]Cordell HJ: Epistasis: what it means, what it doesn't mean, and statistical methods to detect it in humans. Hum Mol Genet 2002, 11(20):2463-2468.
• [19]Moore JH, Williams SM: Traversing the conceptual divide between biological and statistical epistasis: systems biology and a more modern synthesis. Bioessays 2005, 27(6):637-646.
• [20]Birchler JA: Reflections on studies of gene expression in aneuploids. Biochem J 2010, 426(2):119-123.
• [21]Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M, Dunham MJ, Amon A: Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 2007, 317(5840):916-924.
• [22]Williams BR, Prabhu VR, Hunter KE, Glazier CM, Whittaker CA, Housman DE, Amon A: Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells. Science 2008, 322(5902):703-709.
• [23]Makarevitch I, Phillips RL, Springer NM: Profiling expression changes caused by a segmental aneuploid in maize. BMC Genomics 2008, 9:7. BioMed Central Full Text
• [24]Birchler JA, Fernandez HR, Kavi HH: Commonalities in compensation. Bioessays 2006, 28(6):565-568.
• [25]Freeling M, Thomas BC: Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity. Genome Res 2006, 16(7):805-814.
• [26]Birchler JA, Veitia RA: The gene balance hypothesis: from classical genetics to modern genomics. Plant Cell 2007, 19(2):395-402.
• [27]Papp B, Pal C, Hurst LD: Dosage sensitivity and the evolution of gene families in yeast. Nature 2003, 424(6945):194-197.
• [28]Edger PP, Pires JC: Gene and genome duplications: the impact of dosage-sensitivity on the fate of nuclear genes. Chromosome Res 2009, 17(5):699-717.
• [29]Eldar A, Elowitz MB: Functional roles for noise in genetic circuits. Nature 2010, 467(7312):167-173.
• [30]Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS: Global analysis of protein expression in yeast. Nature 2003, 425(6959):737-741.
• [31]Sanjuan R, Elena SF: Epistasis correlates to genomic complexity. Proc Natl Acad Sci USA 2006, 103(39):14402-14405.
• [32]Lenski RE, Ofria C, Collier TC, Adami C: Genome complexity, robustness and genetic interactions in digital organisms. Nature 1999, 400(6745):661-664.
• [33]Bagheri-Chaichian H, Hermisson J, Vaisnys JR, Wagner GP: Effects of epistasis on phenotypic robustness in metabolic pathways. Math Biosci 2003, 184(1):27-51.
• [34]Birchler JA, Veitia RA: The gene balance hypothesis: implications for gene regulation, quantitative traits and evolution. New Phytol 2010, 186(1):54-62.
• [35]Conant GC, Wolfe KH: Increased glycolytic flux as an outcome of whole-genome duplication in yeast. Molecular Systems Biology 2007, 3:129.
• [36]Lunzer M, Golding GB, Dean AM: Pervasive cryptic epistasis in molecular evolution. PLoS Genet 2010, 6(10):e1001162.
• [37]Blake WJ, Kærn M, Cantor CR, Collins JJ: Noise in eukaryotic gene expression. Nature 2003, 422(6932):633-637.
• [38]Shinar G, Feinberg M: Structural sources of robustness in biochemical reaction networks. Science 2010, 327(5971):1389-1391.
• [39]Kacser H, Burns JA: The molecular basis of dominance. Genetics 1981, 97(3-4):639-666.
• [40]Ferrell JE Jr: Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 2002, 14(2):140-148.
• [41]Yu RC, Pesce CG, Colman-Lerner A, Lok L, Pincus D, Serra E, Holl M, Benjamin K, Gordon A, Brent R: Negative feedback that improves information transmission in yeast signalling. Nature 2008, 456(7223):755-761.
• [42]Acar M, Pando BF, Arnold FH, Elowitz MB, van Oudenaarden A: A general mechanism for network-dosage compensation in gene circuits. Science 2010, 329(5999):1656-1660.
• [43]Salwinski L, Miller CS, Smith AJ, Pettit FK, Bowie JU, Eisenberg D: The Database of Interacting Proteins: 2004 update. Nucleic Acids Res 2004, (32 Database):D449-451.
• [44]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: Transcriptional regulatory code of a eukaryotic genome. Nature 2004, 431(7004):99-104.
• [45]Hilbe J: Logistic regression models. Boca Raton: CRC Press; 2009.
• [46]R Development Core Team: R: A language and environment for statistical computing. R Foundation for Statistical Computing; 2008.