A functional selection model explains evolutionary robustness despite plasticity in regulatory networks
Open accessAbstract
Evolutionary rewiring of regulatory networks is an important source of diversity among species. Previous evidence suggested substantial divergence of regulatory networks across species. However, systematically assessing the extent of this plasticity and its functional implications has been challenging due to limited experimental data and the noisy nature of computational predictions. Here, we introduce a novel approach to study cis-regulatory evolution, and use it to trace the regulatory history of 88 DNA motifs of transcription factors across 23 Ascomycota fungi. While motifs are conserved, we find a pervasive gain and loss in the regulation of their target genes. Despite this turnover, the biological processes associated with a motif are generally conserved. We explain these trends using a model with a strong selection to conserve the overall function of a transcription factor, and a much weaker selection over the specific genes it targets. The model also accounts for the turnover of bound targets measured experimentally across species in yeasts and mammals. Thus, selective pressures on regulatory networks mostly tolerate local rewiring, and may allow for subtle fine-tuning of gene regulation during evolution.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Evolution of genetic signaling and regulatory systems usually proceeds through gene duplication and loss with neofunctionalization and subfunctionalization leading to functional changes.
“Evolution of genetic signaling and regulatory systems usually proceeds through gene duplication and loss with concomitant processes of neofunctionalization and subfunctionalization leading to functional changes”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Habib et al. 2012
The Introduction reports widespread gain and loss of regulatory target genes, and Results (‘Innovations through expansion and switch of functions’; page unavailable) says this sometimes expands or switches a motif’s function. The paper does not describe gene duplication with neofunctionalization and subfunctionalization as the usual route of regulatory evolution; it instead says the associated biological processes are typically conserved. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe evolutionary scenario is consistent with a model proposing strong selection of the conservation of the overall function of a transcription control pathway with weaker selection on the specific genes it targets.
“Such an evolutionary scenario is consistent with a model proposing strong selection of the conservation of the overall function of a transcription control pathway with a weaker selection on the specific genes it targets that was previously proposed in Ascomycota (Habib et al. 2012).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Habib et al. 2012
Enhancer conservation is typically modular, commonly preserving the sets of binding sites for the required transcription factors, but often not their exact sequence and orientation.
“Instead, enhancer conservation is typically “modular”, commonly preserving the sets of binding sites for the required TFs, but often not their exact sequence and orientation [101–109].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [105]
The Results section on functional conservation of regulatory DNA motifs describes conserved motif–function associations, while the Discussion describes turnover of target genes within functional modules. Neither passage addresses whether individual enhancers preserve sets of transcription-factor binding sites while their exact sequences and orientations change; searches for enhancer conservation, binding-site sequence, and orientation did not establish that claim. (LLM, conf=0.73)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
KEGG: Kyoto Encyclopedia of Genes and Genomes
Kanehisa, M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.27 · Cited by 37,077 · see citing works
KEGG: Kyoto Encyclopedia of Genes and Genomes
Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., & Kanehisa, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.29 · Cited by 31,232 · see citing works
Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216 · see citing works
Guindon, S., Dufayard, J.-F., Lefort, V., Anisimova, M., Hordijk, W., & Gascuel, O. (2010) · Systematic Biology · doi:10.1093/sysbio/syq010 · Cited by 18,376 · see citing works
Evolutionary trees from DNA sequences: A maximum likelihood approach.
Felsenstein, J. (1981) · Journal of Molecular Evolution · doi:10.1007/bf01734359 · Cited by 14,571 · see citing works
Toward Defining the Course of Evolution: Minimum Change for a Specific Tree Topology
Fitch, W. M. (1971) · Systematic Biology · doi:10.1093/sysbio/20.4.406 · Cited by 7,690 · see citing works
Initial sequencing and comparative analysis of the mouse genome
Mouse Genome Sequencing Consortium (2002) · Nature · doi:10.1038/nature01262 · Cited by 7,187 · see citing works
Molecular signatures database (MSigDB) 3.0
Liberzon, A., Subramanian, A., Pinchback, R., Thorvaldsdóttir, H., Tamayo, P., & Mesirov, J. P. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr260 · Cited by 7,111 · see citing works
Toward Defining the Course of Evolution: Minimum Change for a Specific Tree Topology
Fitch, W. M. (1971) · Systematic Zoology · doi:10.2307/2412116 · Cited by 5,661 · see citing works
Fitting a mixture model by expectation maximization to discover motifs in biopolymers.
Bailey, T. L., & Elkan, C. (1994) · PubMed · Cited by 4,933 · see citing works
Network motifs: theory and experimental approaches
Alon, U. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2102 · Cited by 3,279 · see citing works
From genomics to chemical genomics: new developments in KEGG
Kanehisa, M. I. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj102 · Cited by 3,126 · see citing works
King, M.-C., & Wilson, A. C. (1975) · Science · doi:10.1126/science.1090005 · Cited by 2,815 · see citing works
Functional Discovery via a Compendium of Expression Profiles
Hughes, T. R., Marton, M. J., Jones, A. R., Roberts, C. J., Stoughton, R. B., Armour, C. D., Bennett, H. A., Coffey, E. M., Dai, H. A., He, Y. D., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)00015-5 · Cited by 2,534 · see citing works
TRANSFAC(R) and its module TRANSCompel(R): transcriptional gene regulation in eukaryotes
Matys, V. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj143 · Cited by 2,142 · see citing works
Transcriptional regulatory code of a eukaryotic genome
Harbison, C. T., Gordon, D. B., Lee, T. I., Rinaldi, N. J., MacIsaac, K. D., Danford, T., Hannett, N. M., Tagne, J., Reynolds, D. B., Yoo, J. Y., et al. (2004) · Nature · doi:10.1038/nature02800 · Cited by 2,116 · see citing works
Sequencing and comparison of yeast species to identify genes and regulatory elements
Kellis, M., Patterson, N. J., Endrizzi, M. G., Birren, B. W., & Lander, E. S. (2003) · Nature · doi:10.1038/nature01644 · Cited by 1,731 · see citing works
Segal, E., Shapira, M., Regev, A., Pe’er, D., Botstein, D., Koller, D., & Friedman, N. (2003) · Nature Genetics · doi:10.1038/ng1165 · Cited by 1,686 · see citing works
Self-citationThe genome sequence of Schizosaccharomyces pombe
Wood, V., Gwilliam, R., Rajandream, M.-A., Lyne, M. H., Lyne, R., Stewart, A., SGOUROS, J. G., Peat, N., Hayles, J., Baker, S. G., et al. (2002) · Nature · doi:10.1038/nature724 · Cited by 1,650 · see citing works
Dujon, B., Sherman, D., Fischer, G., Durrens, P., Casaregola, S., Lafontaine, I., de Montigny, J., Marck, C., Neuvéglise, C., Talla, E., et al. (2004) · Nature · doi:10.1038/nature02579 · Cited by 1,623 · see citing works
Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae
Kellis, M., Birren, B. W., & Lander, E. S. (2004) · Nature · doi:10.1038/nature02424 · Cited by 1,500 · see citing works
Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae
Galagan, J. E., Calvo, S. E., Cuomo, C. A., Ma, L., Wortman, J. R., Batzoglou, S., Lee, S., Baştürkmen, M., Spevak, C. C., Clutterbuck, J., et al. (2005) · Nature · doi:10.1038/nature04341 · Cited by 1,359 · see citing works
A high-resolution map of human evolutionary constraint using 29 mammals
Broad Institute Sequencing Platform and Whole Genome Assembly Team, Lindblad-Toh, K., Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Genome Institute at Washington University, Garber, M., Zuk, O., Lin, M. F., Parker, B. J., Washietl, S., Kheradpour, P., et al. (2011) · Nature · doi:10.1038/nature10530 · Cited by 1,108 · see citing works
Evolution of pathogenicity and sexual reproduction in eight Candida genomes
Butler, G., Rasmussen, M. D., Lin, M. F., Santos, M. A. S., Sakthikumar, S., Munro, C. A., Rheinbay, E., Grabherr, M., Forche, A., Reedy, J. L., et al. (2009) · Nature · doi:10.1038/nature08064 · Cited by 1,065 · see citing works
Evolutionary changes in cis and trans gene regulation
Wittkopp, P. J., Haerum, B. K., & Clark, A. G. (2004) · Nature · doi:10.1038/nature02698 · Cited by 873 · see citing works
Finding Functional Features in Saccharomyces Genomes by Phylogenetic Footprinting
Cliften, P. F., Sudarsanam, P., Desikan, A., Fulton, L. A., Fulton, B., Majors, J. E., Waterston, R., Cohen, B. A., & Johnston, M. (2003) · Science · doi:10.1126/science.1084337 · Cited by 805 · see citing works
Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice
Ortega, S., Priéto, I., Odajima, J., Martín, A. L., Dubus, P. R., Sotillo, R., Barbero, J. L., Malumbres, M., & Barbacid, M. (2003) · Nature Genetics · doi:10.1038/ng1232 · Cited by 798 · see citing works
Global transcriptional responses of fission yeast to environmental stress
Chen, D., Toone, W. M., Mata, J., Lyne, R., Burns, G., Kivinen, K., Brazma, A., Jones, N., & Bähler, J. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-08-0499 · Cited by 796 · see citing works
The barite-opal-organic carbon association in oceanic particulate matter
Bishop, J. K. B. (1988) · Nature · doi:10.1038/332341a0 · Cited by 724 · see citing works
Five-Vertebrate ChIP-seq Reveals the Evolutionary Dynamics of Transcription Factor Binding
Schmidt, D., Wilson, M. D., Ballester, B., Schwalie, P. C., Brown, G. D., Marshall, A., Kutter, C., Watt, S., Martinez-Jimenez, C. P., Mackay, S., et al. (2010) · Science · doi:10.1126/science.1186176 · Cited by 700 · see citing works
The Ashbya gossypii Genome as a Tool for Mapping the Ancient Saccharomyces cerevisiae Genome
Dietrich, F. S., Voegeli, S., Brachat, S., Lerch, A., Gates, K., Steiner, S., Mohr, C., Pöhlmann, R., Luedi, P. P., Choi, S., et al. (2004) · Science · doi:10.1126/science.1095781 · Cited by 631 · see citing works
Natural history and evolutionary principles of gene duplication in fungi
Wapinski, I., Pfeffer, A., Friedman, N., & Regev, A. (2007) · Nature · doi:10.1038/nature06107 · Cited by 614 · see citing works
Self-citationEmerging principles of regulatory evolution
Prud’homme, B., Gompel, N., & Carroll, S. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700488104 · Cited by 556 · see citing works
Tissue-specific transcriptional regulation has diverged significantly between human and mouse
Odom, D. T., Dowell, R. D., Jacobsen, E. S., Gordon, W., Danford, T. W., MacIsaac, K. D., Rolfe, P. A., Conboy, C. M., Gifford, D. K., & Fraenkel, E. (2007) · Nature Genetics · doi:10.1038/ng2047 · Cited by 506 · see citing works
Nehlin, J. O., & Ronne, H. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07479.x · Cited by 486 · see citing works
Comparative functional genomics of the fission yeasts
Rhind, N., Chen, Z., Yassour, M., Thompson, D. A., Haas, B. J., Habib, N., Wapinski, I., Roy, S., Lin, M. F., Heiman, D. I., et al. (2011) · Science · doi:10.1126/science.1203357 · Cited by 484 · see citing works
Self-citation[57] Genetic and physical maps of Saccharomyces cerevisiae
Mortimer, R., Schild, D., Contopoulou, C. R., & Kans, J. A. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)94060-p · Cited by 473 · see citing works
Multiple rounds of speciation associated with reciprocal gene loss in polyploid yeasts
Scannell, D. R., Byrne, K. P., Gordon, J., Wong, S., & Wolfe, K. H. (2006) · Nature · doi:10.1038/nature04562 · Cited by 429 · see citing works
A Yeast Hybrid Provides Insight into the Evolution of Gene Expression Regulation
Tirosh, I., Reikhav, S., Levy, A. A., & Barkai, N. (2009) · Science · doi:10.1126/science.1169766 · Cited by 399 · see citing works
High-resolution DNA-binding specificity analysis of yeast transcription factorsPreprint
Zhu, C., Byers, K. J. R. P., McCord, R. P., Shi, Z., Berger, M. F., Newburger, D. E., Saulrieta, K., Smith, Z. D., Shah, M. V., Radhakrishnan, M., et al. (2009) · Genome Research · doi:10.1101/gr.090233.108 · Cited by 399 · see citing works
Regulatory changes underlying expression differences within and between Drosophila species
Wittkopp, P. J., Haerum, B. K., & Clark, A. G. (2008) · Nature Genetics · doi:10.1038/ng.77 · Cited by 367 · see citing works
Evolution of primate gene expression
Khaitovich, P., Enard, W., Lachmann, M., & Pääbo, S. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1940 · Cited by 341 · see citing works
Divergence of Transcription Factor Binding Sites Across Related Yeast Species
Borneman, A. R., Gianoulis, T. A., Zhang, Z. D., Yu, H., Rozowsky, J. S., Seringhaus, M. R., Wang, L.-Y., Gerstein, M., & Snyder, M. P. (2007) · Science · doi:10.1126/science.1140748 · Cited by 335 · see citing works
Species-Specific Transcription in Mice Carrying Human Chromosome 21
Wilson, M. D., Barbosa‐Morais, N. L., Schmidt, D., Conboy, C. B., Vanes, L., Tybulewicz, V. L. J., Fisher, E., Tavaré, S., & Odom, D. T. (2008) · Science · doi:10.1126/science.1160930 · Cited by 280 · see citing works
Splitting vessels: Keeping lymph apart from blood
Rafii, S., & Skobe, M. (2003) · Nature Medicine · doi:10.1038/nm0203-166 · Cited by 264 · see citing works
Conservation and evolvability in regulatory networks: The evolution of ribosomal regulation in yeast
Tanay, A., Regev, A., & Ron Shamir, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502521102 · Cited by 262 · see citing works
Self-citationCytoplasmic fatty acid‐binding protein facilitates fatty acid utilization by skeletal muscle
Glatz, J. F. C., Schaap, F. G., Binas, B., Bonen, A., Vusse, G. J., & Luiken, J. J. F. P. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01166.x · Cited by 259 · see citing works
Evolution of alternative transcriptional circuits with identical logic
Tsong, A. E., Tuch, B. B., Li, H., & Johnson, A. D. (2006) · Nature · doi:10.1038/nature05099 · Cited by 255 · see citing works
Large-Scale Turnover of Functional Transcription Factor Binding Sites in Drosophila
Moses, A. M., Pollard, D. A., Nix, D. A., Iyer, V. N., Li, X., Biggin, M. D., & Eisen, M. B. (2006) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020130 · Cited by 251 · see citing works
Extensive low-affinity transcriptional interactions in the yeast genomePreprint
Tanay, A. (2006) · Genome Research · doi:10.1101/gr.5113606 · Cited by 244 · see citing works
Structure and function of a transcriptional network activated by the MAPK Hog1
Capaldi, A. P., Kaplan, T., Liu, Y., Habib, N., Regev, A., Friedman, N., & O’Shea, E. K. (2008) · Nature Genetics · doi:10.1038/ng.235 · Cited by 233 · see citing works
Self-citationThe evolution of combinatorial gene regulation in fungi
Tuch, B. B., Galgoczy, D. J., Hernday, A. D., Li, H., & Johnson, A. D. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060038 · Cited by 228 · see citing works
Conservation and Evolution of Cis-Regulatory Systems in Ascomycete Fungi
Gasch, A. P., Moses, A. M., Chiang, D. Y., Fraser, H. B., Berardini, M. D., & Eisen, M. B. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020398 · Cited by 227 · see citing works
Bradley, R. K., Li, X., Trapnell, C., Davidson, S. M., Pachter, L. S., Chu, H. C., Tonkin, L. A., Biggin, M. D., & Eisen, M. B. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000343 · Cited by 186 · see citing works
Frequent Gain and Loss of Functional Transcription Factor Binding Sites
Doniger, S. W., & Fay, J. C. (2005) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030099 · Cited by 152 · see citing works
Gene amplification and gene correction in somatic cells
Roberts, J. M., & Axel, R. (1982) · Cell · doi:10.1016/0092-8674(82)90095-2 · Cited by 150 · see citing works
Weirauch, M. T., & Hughes, T. R. (2010) · Trends in Genetics · doi:10.1016/j.tig.2009.12.002 · Cited by 146 · see citing works
Structural features in a brittle–ductile wax model of continental extension
Brune, J. N., & Ellis, M. A. (1997) · Nature · doi:10.1038/387067a0 · Cited by 145 · see citing works
Evolutionary Tinkering with Conserved Components of a Transcriptional Regulatory Network
Lavoie, H., Hogues, H., Mallick, J., Sellam, A., Nantel, A., & Whiteway, M. S. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000329 · Cited by 133 · see citing works
A Structural EM Algorithm for Phylogenetic Inference
Friedman, N., Ninio, M., Pe’er, I., & Pupko, T. (2002) · Journal of Computational Biology · doi:10.1089/10665270252935494 · Cited by 129 · see citing works
Self-citationSouth African museums' status ‘at risk’
Cherry, M. L. (1997) · Nature · doi:10.1038/43025 · Cited by 122 · see citing works
Transcription Factor Substitution during the Evolution of Fungal Ribosome Regulation
Hogues, H., Lavoie, H., Sellam, A., Mangos, M., Roemer, T., Purisima, E. O., Nantel, A., & Whiteway, M. S. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.02.006 · Cited by 109 · see citing works
Eukaryotic transcription factor binding sites—modeling and integrative search methods
Hannenhalli, S. S. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn198 · Cited by 106 · see citing works
MIPS: curated databases and comprehensive secondary data resources in 2010
Mewes, H., Ruepp, A., Theis, F. J., Rattei, T., Walter, M. C., Frishman, D., Suhre, K., Spannagl, M., Mayer, K., Stümpflen, V., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1157 · Cited by 100 · see citing works
Sequence resources at the Candida Genome Database
Arnaud, M. B., Costanzo, M. C., Skrzypek, M. S., Shah, P., Binkley, G., Lane, C. D., Miyasato, S. R., & Sherlock, G. J. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl899 · Cited by 73 · see citing works
From elements to modules: regulatory evolution in Ascomycota fungi
Wohlbach, D. J., Thompson, D. A., Gasch, A. P., & Regev, A. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.09.007 · Cited by 50 · see citing works
Self-citationA Novel Bayesian DNA Motif Comparison Method for Clustering and Retrieval
Habib, N., Kaplan, T., Margalit, H., & Friedman, N. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000010 · Cited by 49 · see citing works
Self-citationEvolution of Cell Cycle Control: Same Molecular Machines, Different Regulation
de Lichtenberg, U., Jensen, T. S., Brunak, S., Peer Bork, B., & Jensen, L. J. (2007) · Cell Cycle · doi:10.4161/cc.6.15.4537 · Cited by 36 · see citing works
Transcriptional Activation Domains of the Candida albicans Gcn4p and Gal4p Homologs
Martchenko, M., Levitin, A., & Whiteway, M. S. (2006) · Eukaryotic Cell · doi:10.1128/ec.00183-06 · Cited by 26 · see citing works
Genomic Evolution of the Proteasome System Among Hemiascomycetous Yeasts
Mannhaupt, G., & Feldmann, H. (2007) · Journal of Molecular Evolution · doi:10.1007/s00239-007-9031-y · Cited by 19 · see citing works
Shaw, C. H., Ashby, A. M., & Watson, M. D. (1986) · Nature · doi:10.1038/324415b0 · Cited by 12 · see citing works
An improved map of conserved regulatory sites for Saccharomyces cerevisiae
MacIsaac, K. D., Wang, T., Gordon, D. B., Gifford, D. K., Stormo, G. D., & Fraenkel, E. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-113 · Cited by 9 · see citing works
Nature of the Leucocytosis-inducing Factor in Plasma
FUKUDA, T., Oide, H., & MIYASAKA, A. (1960) · Nature · doi:10.1038/188860b0 · Cited by 9 · see citing works
Battle lines are drawn as French researchers resign en masse
Butler, D. (2004) · Nature · doi:10.1038/428241a · Cited by 2 · see citing works
Note upon the Habits of Testacella
Poulton, E. B. (1886) · Nature · doi:10.1038/034617c0 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The evolution, evolvability and engineering of gene regulatory DNA
Vaishnav, E. D., de Boer, C. G., Molinet, J., Yassour, M., Fan, L., Adiconis, X., Thompson, D. A., Levin, J. Z., Cubillos, F. A., & Regev, A. (2022) · Nature · doi:10.1038/s41586-022-04506-6 · Cited by 279 · see citing works
Self-citationComparative Analysis of Gene Regulatory Networks: From Network Reconstruction to Evolution
Thompson, D. A., Regev, A., & Roy, S. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100913-012908 · Cited by 170 · see citing works
Self-citationPitkänen, E., Jouhten, P., Hou, J., Syed, M. F., Blomberg, P., Kludas, J., Oja, M., Holm, L., Penttilä, M. E., Rousu, J., et al. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003465 · Cited by 116 · see citing works
Spurious transcription factor binding: Non‐functional or genetically redundant?
Spivakov, M. (2014) · BioEssays · doi:10.1002/bies.201400036 · Cited by 96 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
Evolutionary principles of modular gene regulation in yeasts
Thompson, D. A., Roy, S., Chan, M., Styczynsky, M. P., Pfiffner, J., French, C., Socha, A., Thielke, A., Napolitano, S., Muller, P., et al. (2013) · eLife · doi:10.7554/elife.00603 · Cited by 78 · see citing works
Self-citationMaguire, S. L., Wang, C., Holland, L. M., Brunel, F., Neuvéglise, C., Nicaud, J.-M., Zavrel, M., White, T. C., Wolfe, K. H., & Butler, G. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004076 · Cited by 69 · see citing works
SH3 interactome conserves general function over specific form
Xin, X., Gfeller, D., Cheng, J. C., Tonikian, R., Sun, L., Guo, A., Lopez, L., Pavlenco, A., Akintobi, A., Zhang, Y., et al. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.9 · Cited by 64 · see citing works
Wang, E., Zou, J., Zaman, N., Beitel, L. K., Trifiro, M. A., & Paliouras, M. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.06.001 · Cited by 69 · see citing works
The rewiring of transcription circuits in evolution
Johnson, A. D. (2017) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2017.09.004 · Cited by 59 · see citing works
Evolutionary Conservation and Diversification of Puf RNA Binding Proteins and Their mRNA Targets
Hogan, G. J., Brown, P. O., & Herschlag, D. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002307 · Cited by 55 · see citing works
Roy, S., Wapinski, I. N., Pfiffner, J., French, C. E., Socha, A. L., Konieczka, J. H., Habib, N., Kellis, M., Thompson, D. A., & Regev, A. (2013) · Genome Research · doi:10.1101/gr.146233.112 · Cited by 55 · see citing works
Self-citationInference and Evolutionary Analysis of Genome-Scale Regulatory Networks in Large Phylogenies
Koch, C., Konieczka, J. H., Delorey, T. M., Lyons, A. M., Socha, A. L., Davis, K., Knaack, S., Thompson, D. A., O’Shea, E. K., Regev, A., et al. (2017) · Cell Systems · doi:10.1016/j.cels.2017.04.010 · Cited by 48 · see citing works
Self-citationEvolutionary dynamics of microRNA target sites across vertebrate evolution
Simkin, A., Geißler, R., McIntyre, A. B. R., & Grimson, A. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008285 · Cited by 43 · see citing works
Function does not follow form in gene regulatory circuits
Payne, J. L., & Wagner, A. (2015) · Scientific Reports · doi:10.1038/srep13015 · Cited by 41 · see citing works
Biophysical Fitness Landscapes for Transcription Factor Binding Sites
Haldane, A., Manhart, M., & Morozov, A. V. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003683 · Cited by 39 · see citing works
Identifying Network Perturbation in Cancer
Grechkin, M., Logsdon, B. A., Gentles, A. J., & Lee, S. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004888 · Cited by 36 · see citing works
Constraint and Contingency in Multifunctional Gene Regulatory Circuits
Payne, J. L., & Wagner, A. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003071 · Cited by 34 · see citing works
Phylogenetic Relationships Matter: Antifungal Susceptibility among Clinically Relevant Yeasts
Schmalreck, A., Lackner, M., Becker, K., Fegeler, W., Czaika, V. A., Ulmer, H., & Lass‐Flörl, C. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01799-13 · Cited by 34 · see citing works
Dalal, C. K., & Johnson, A. D. (2017) · Genes & Development · doi:10.1101/gad.303362.117 · Cited by 26 · see citing works
He, B. Z., Zhou, X., & O’Shea, E. K. (2017) · eLife · doi:10.7554/elife.25157 · Cited by 27 · see citing works
The Evolution of Human Cells in Terms of Protein Innovation
Sardar, A. J., Oates, M. E., Fang, H., Forrest, A. R. R., Kawaji, H., Gough, J., & Rackham, O. J. L. (2014) · Molecular Biology and Evolution · doi:10.1093/molbev/mst139 · Cited by 23 · see citing works
Patterns of Conservation and Diversification in the Fungal Polarization Network
Diepeveen, E. T., Gehrmann, T., Pourquié, V., Abeel, T., & Laan, L. (2018) · Genome Biology and Evolution · doi:10.1093/gbe/evy121 · Cited by 22 · see citing works
Shrivastava, M., Kouyoumdjian, G. S., Kirbizakis, E., Ruiz, D., Henry, M., Vincent, A. T., Sellam, A., & Whiteway, M. S. (2023) · mBio · doi:10.1128/mbio.01807-23 · Cited by 22 · see citing works
Mallick, J., & Whiteway, M. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.436683 · Cited by 21 · see citing works
Systems biology approaches to defining transcription regulatory networks in halophilic archaea
Darnell, C. L., & Schmid, A. (2015) · Methods · doi:10.1016/j.ymeth.2015.04.034 · Cited by 18 · see citing works
Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells
Mellis, I. A., Melzer, M. E., Bodkin, N., & Goyal, Y. (2024) · Genome biology · doi:10.1186/s13059-024-03351-2 · Cited by 15 · see citing works
Natural gene expression variation studies in yeast
Thompson, D. A., & Cubillos, F. A. (2016) · Yeast · doi:10.1002/yea.3210 · Cited by 14 · see citing works
Global coordination in adaptation to gene rewiring
Murakami, Y., Matsumoto, Y., Tsuru, S., Ying, B., & Yomo, T. (2015) · Nucleic Acids Research · doi:10.1093/nar/gku1366 · Cited by 12 · see citing works
Berke, L., & Snel, . (2014) · Genome Biology and Evolution · doi:10.1093/gbe/evu040 · Cited by 13 · see citing works
High-Throughput Identification ofCis-Regulatory Rewiring Events in Yeast
Sarda, S., & Hannenhalli, S. S. (2015) · Molecular Biology and Evolution · doi:10.1093/molbev/msv203 · Cited by 12 · see citing works
Systematic and synthetic approaches to rewire regulatory networks
Park, J., & Wang, H. H. (2018) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2017.12.009 · Cited by 11 · see citing works
FUN-PROSE: A deep learning approach to predict condition-specific gene expression in fungi
Nambiar, A., Dubinkina, V. B., Liu, S., & Maslov, S. (2023) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1011563 · Cited by 10 · see citing works
Assessment of transfer methods for comparative genomics of regulatory networks in bacteria
Kılıç, S., & Erill, I. (2016) · BMC Bioinformatics · doi:10.1186/s12859-016-1113-7 · Cited by 10 · see citing works
Benchouaia, M., Ripoche, H., Sissoko, M., Thiébaut, A., Merhej, J., Delaveau, T., Fasseu, L., Benaissa, S., Lorieux, G., Jourdren, L., et al. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02689 · Cited by 8 · see citing works
Muñoz, A., MuĂąoz, D. S., Zimin, A. V., & Yorke, J. A. (2016) · BMC Genomics · doi:10.1186/s12864-016-3102-7 · Cited by 7 · see citing works
Evolution of regulatory networks inCandida glabrata: learning to live with the human host
Roy, S., & Thompson, D. A. (2015) · FEMS Yeast Research · doi:10.1093/femsyr/fov087 · Cited by 7 · see citing works
Functional duplication of Rap1 in methylotrophic yeasts
Malyavko, A. N., Petrova, O. A., Zvereva, M. I., & Донцова, О. А. (2019) · Scientific Reports · doi:10.1038/s41598-019-43595-8 · Cited by 5 · see citing works
Mutations in Transcriptional Regulators Allow Selective Engineering of Signal Integration Logic
Semsey, S. (2014) · mBio · doi:10.1128/mbio.01171-14 · Cited by 4 · see citing works
Extensive binding of poorly characterized human transcription factors to genomic dark matter
Razavi, R., Fathi, A., Yellan, I., Brechalov, A. V., Laverty, K. U., Jolma, A., Hernández-Corchado, A., Zheng, H., Yang, A. W. H., Albu, M., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-75376-z · Cited by 11 · see citing works
Knaack, S., Thompson, D. A., & Roy, S. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3079-1_21 · Cited by 2 · see citing works
Enabling Studies of Genome-Scale Regulatory Network Evolution in Large Phylogenies with MRTLE
Zhang, S., Knaack, S., & Roy, S. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2257-5_24 · Cited by 2 · see citing works
Vaishnav, E. D., de Boer, C. G., Yassour, M., Molinet, J., Fan, L., Adiconis, X., Thompson, D. A., Cubillos, F. A., Levin, J. Z., & Regev, A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.17.430503 · Cited by 2 · see citing works
Self-citationShrivastava, M., Kouyoumdjian, G. S., Kirbizakis, E., Ruiz, D., Henry, M., Vincent, A. T., Sellam, A., & Whiteway, M. S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.24.524502 · Cited by 2 · see citing works
Łabędzka-Dmoch, K., Bui, T. H. D., Piątkowski, J., Dilling, M., Jagiełło, P., Kabza, W., & Golik, P. (2026) · Molecular Biology and Evolution · doi:10.1093/molbev/msag005 · Cited by 1 · see citing works
Robustness and plasticity in network evolution
Flintoft, L. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3383 · Cited by 1 · see citing works
Prevalence of and gene regulatory constraints on transcriptional adaptation in single cellsPreprint
Mellis, I. A., Bodkin, N., Melzer, M. E., & Goyal, Y. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.14.553318 · Cited by 1 · see citing works
Comparative Transcriptomics in Yeasts
Thompson, D. A. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3079-1_4
Biophysical models of evolution
Haldane, A. (2014) · doi:10.7282/t3bg2m24
Transcriptional networks of the stress responses in the human pathogen Candida glabrata
Thiébaut, A. (2018) · theses.fr (ABES) · doi:10.70675/323c74a8z1ae4z4123za081zd0af3ecf65ae
- Authors
- Habib, N., Wapinski, I., Margalit, H., Regev, A., & Friedman, N.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Broad Institute (US)
- Corresponding author
- Margalit, Hanah
- Regev, Aviv
- Friedman, Nir
- Venue
- Molecular Systems Biology
- Published
- 2012-10-23
- Volume
- 8
- Issue
- 1
- Pages
- 619-619
- ISSN
- 1744-4292 (ISSN-L)
- PMC
- PMC3501536
- OpenAlex
- W2142265915
- Cited by
- 50
- References
- 76
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 9 · 2014: 8 · 2013: 7 · 2012: 1
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Systems Biology (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- Howard Hughes Medical Institute
- Alfred P. Sloan Foundation
- Damon Runyon Cancer Research Foundation
- National Institutes of Health (5r01ca119176-10, NIH-R01, 2R01CA119176-01)
- National Cancer Institute (R01 2R01CA119176-01, DP1CA174427, R01-CA119176)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- cis-regulatory evolution
- MeSH terms
- Animals, Ascomycota, Base Sequence, DNA, Fungal, Fungal Proteins, Mammals, Models, Genetic, Molecular Sequence Data, Phylogeny, Protein Binding, Regulatory Sequences, Nucleic Acid, Selection, Genetic, Species Specificity, Transcription Factors, Conserved Sequence, Evolution, Molecular, Gene Regulatory Networks, Nucleotide Motifs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
