Modeling the evolution of a classic genetic switch

Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding...
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Autor*in:	Josephides, Christos [verfasserIn] Moses, Alan M

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2011

Schlagwörter:	Evolutionary Change Evolutionary Path Whole Genome Duplication Upstream Activation Sequence Stochastic Part

Anmerkung:	© Josephides and Moses; licensee BioMed Central Ltd. 2011

Übergeordnetes Werk:	Enthalten in: BMC systems biology - London : BioMed Central, 2007, 5(2011), 1 vom: 05. Feb.
Übergeordnetes Werk:	volume:5 ; year:2011 ; number:1 ; day:05 ; month:02

Links:	Volltext

DOI / URN:	10.1186/1752-0509-5-24

Katalog-ID:	SPR028409884

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520			\|a Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution.
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allfields	10.1186/1752-0509-5-24 doi (DE-627)SPR028409884 (SPR)1752-0509-5-24-e DE-627 ger DE-627 rakwb eng Josephides, Christos verfasserin aut Modeling the evolution of a classic genetic switch 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Josephides and Moses; licensee BioMed Central Ltd. 2011 Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution. Evolutionary Change (dpeaa)DE-He213 Evolutionary Path (dpeaa)DE-He213 Whole Genome Duplication (dpeaa)DE-He213 Upstream Activation Sequence (dpeaa)DE-He213 Stochastic Part (dpeaa)DE-He213 Moses, Alan M aut Enthalten in BMC systems biology London : BioMed Central, 2007 5(2011), 1 vom: 05. Feb. (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:5 year:2011 number:1 day:05 month:02 https://dx.doi.org/10.1186/1752-0509-5-24 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2011 1 05 02
spelling	10.1186/1752-0509-5-24 doi (DE-627)SPR028409884 (SPR)1752-0509-5-24-e DE-627 ger DE-627 rakwb eng Josephides, Christos verfasserin aut Modeling the evolution of a classic genetic switch 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Josephides and Moses; licensee BioMed Central Ltd. 2011 Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution. Evolutionary Change (dpeaa)DE-He213 Evolutionary Path (dpeaa)DE-He213 Whole Genome Duplication (dpeaa)DE-He213 Upstream Activation Sequence (dpeaa)DE-He213 Stochastic Part (dpeaa)DE-He213 Moses, Alan M aut Enthalten in BMC systems biology London : BioMed Central, 2007 5(2011), 1 vom: 05. Feb. (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:5 year:2011 number:1 day:05 month:02 https://dx.doi.org/10.1186/1752-0509-5-24 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2011 1 05 02
allfields_unstemmed	10.1186/1752-0509-5-24 doi (DE-627)SPR028409884 (SPR)1752-0509-5-24-e DE-627 ger DE-627 rakwb eng Josephides, Christos verfasserin aut Modeling the evolution of a classic genetic switch 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Josephides and Moses; licensee BioMed Central Ltd. 2011 Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution. Evolutionary Change (dpeaa)DE-He213 Evolutionary Path (dpeaa)DE-He213 Whole Genome Duplication (dpeaa)DE-He213 Upstream Activation Sequence (dpeaa)DE-He213 Stochastic Part (dpeaa)DE-He213 Moses, Alan M aut Enthalten in BMC systems biology London : BioMed Central, 2007 5(2011), 1 vom: 05. Feb. (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:5 year:2011 number:1 day:05 month:02 https://dx.doi.org/10.1186/1752-0509-5-24 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2011 1 05 02
allfieldsGer	10.1186/1752-0509-5-24 doi (DE-627)SPR028409884 (SPR)1752-0509-5-24-e DE-627 ger DE-627 rakwb eng Josephides, Christos verfasserin aut Modeling the evolution of a classic genetic switch 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Josephides and Moses; licensee BioMed Central Ltd. 2011 Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution. Evolutionary Change (dpeaa)DE-He213 Evolutionary Path (dpeaa)DE-He213 Whole Genome Duplication (dpeaa)DE-He213 Upstream Activation Sequence (dpeaa)DE-He213 Stochastic Part (dpeaa)DE-He213 Moses, Alan M aut Enthalten in BMC systems biology London : BioMed Central, 2007 5(2011), 1 vom: 05. Feb. (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:5 year:2011 number:1 day:05 month:02 https://dx.doi.org/10.1186/1752-0509-5-24 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2011 1 05 02
allfieldsSound	10.1186/1752-0509-5-24 doi (DE-627)SPR028409884 (SPR)1752-0509-5-24-e DE-627 ger DE-627 rakwb eng Josephides, Christos verfasserin aut Modeling the evolution of a classic genetic switch 2011 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Josephides and Moses; licensee BioMed Central Ltd. 2011 Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution. Evolutionary Change (dpeaa)DE-He213 Evolutionary Path (dpeaa)DE-He213 Whole Genome Duplication (dpeaa)DE-He213 Upstream Activation Sequence (dpeaa)DE-He213 Stochastic Part (dpeaa)DE-He213 Moses, Alan M aut Enthalten in BMC systems biology London : BioMed Central, 2007 5(2011), 1 vom: 05. Feb. (DE-627)522897126 (DE-600)2265490-2 1752-0509 nnns volume:5 year:2011 number:1 day:05 month:02 https://dx.doi.org/10.1186/1752-0509-5-24 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2011 1 05 02
language	English
source	Enthalten in BMC systems biology 5(2011), 1 vom: 05. Feb. volume:5 year:2011 number:1 day:05 month:02
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topic_facet	Evolutionary Change Evolutionary Path Whole Genome Duplication Upstream Activation Sequence Stochastic Part
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We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. 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author	Josephides, Christos
spellingShingle	Josephides, Christos misc Evolutionary Change misc Evolutionary Path misc Whole Genome Duplication misc Upstream Activation Sequence misc Stochastic Part Modeling the evolution of a classic genetic switch
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topic_title	Modeling the evolution of a classic genetic switch Evolutionary Change (dpeaa)DE-He213 Evolutionary Path (dpeaa)DE-He213 Whole Genome Duplication (dpeaa)DE-He213 Upstream Activation Sequence (dpeaa)DE-He213 Stochastic Part (dpeaa)DE-He213
topic	misc Evolutionary Change misc Evolutionary Path misc Whole Genome Duplication misc Upstream Activation Sequence misc Stochastic Part
topic_unstemmed	misc Evolutionary Change misc Evolutionary Path misc Whole Genome Duplication misc Upstream Activation Sequence misc Stochastic Part
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title	Modeling the evolution of a classic genetic switch
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title_full	Modeling the evolution of a classic genetic switch
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title_sort	modeling the evolution of a classic genetic switch
title_auth	Modeling the evolution of a classic genetic switch
abstract	Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution. © Josephides and Moses; licensee BioMed Central Ltd. 2011
abstractGer	Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution. © Josephides and Moses; licensee BioMed Central Ltd. 2011
abstract_unstemmed	Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution. © Josephides and Moses; licensee BioMed Central Ltd. 2011
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title_short	Modeling the evolution of a classic genetic switch
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Modeling the evolution of a classic genetic switch

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