[{"department":[{"_id":"NiBa"},{"_id":"CaGu"}],"date_updated":"2021-01-12T06:50:08Z","article_type":"original","type":"journal_article","status":"public","_id":"1359","ec_funded":1,"volume":113,"issue":"16","publication_status":"published","language":[{"iso":"eng"}],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843425/","open_access":"1"}],"scopus_import":1,"intvolume":" 113","month":"04","abstract":[{"lang":"eng","text":"The role of gene interactions in the evolutionary process has long\r\nbeen controversial. Although some argue that they are not of\r\nimportance, because most variation is additive, others claim that\r\ntheir effect in the long term can be substantial. Here, we focus on\r\nthe long-term effects of genetic interactions under directional\r\nselection assuming no mutation or dominance, and that epistasis is\r\nsymmetrical overall. We ask by how much the mean of a complex\r\ntrait can be increased by selection and analyze two extreme\r\nregimes, in which either drift or selection dominate the dynamics\r\nof allele frequencies. In both scenarios, epistatic interactions affect\r\nthe long-term response to selection by modulating the additive\r\ngenetic variance. When drift dominates, we extend Robertson\r\n’\r\ns\r\n[Robertson A (1960)\r\nProc R Soc Lond B Biol Sci\r\n153(951):234\r\n−\r\n249]\r\nargument to show that, for any form of epistasis, the total response\r\nof a haploid population is proportional to the initial total genotypic\r\nvariance. In contrast, the total response of a diploid population is\r\nincreased by epistasis, for a given initial genotypic variance. When\r\nselection dominates, we show that the total selection response can\r\nonly be increased by epistasis when s\r\nome initially deleterious alleles\r\nbecome favored as the genetic background changes. We find a sim-\r\nple approximation for this effect and show that, in this regime, it is\r\nthe structure of the genotype - phenotype map that matters and not\r\nthe variance components of the population."}],"oa_version":"Published Version","pmid":1,"article_processing_charge":"No","external_id":{"pmid":["27044080"]},"publist_id":"5886","author":[{"last_name":"Paixao","full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago"},{"first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H","last_name":"Barton"}],"title":"The effect of gene interactions on the long-term response to selection","citation":{"chicago":"Paixao, Tiago, and Nicholas H Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS. National Academy of Sciences, 2016. https://doi.org/10.1073/pnas.1518830113.","ista":"Paixao T, Barton NH. 2016. The effect of gene interactions on the long-term response to selection. PNAS. 113(16), 4422–4427.","mla":"Paixao, Tiago, and Nicholas H. Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS, vol. 113, no. 16, National Academy of Sciences, 2016, pp. 4422–27, doi:10.1073/pnas.1518830113.","ama":"Paixao T, Barton NH. The effect of gene interactions on the long-term response to selection. PNAS. 2016;113(16):4422-4427. doi:10.1073/pnas.1518830113","apa":"Paixao, T., & Barton, N. H. (2016). The effect of gene interactions on the long-term response to selection. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1518830113","short":"T. Paixao, N.H. Barton, PNAS 113 (2016) 4422–4427.","ieee":"T. Paixao and N. H. Barton, “The effect of gene interactions on the long-term response to selection,” PNAS, vol. 113, no. 16. National Academy of Sciences, pp. 4422–4427, 2016."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"_id":"25B07788-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"250152","name":"Limits to selection in biology and in evolutionary computation"},{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"}],"page":"4422 - 4427","date_created":"2018-12-11T11:51:34Z","date_published":"2016-04-19T00:00:00Z","doi":"10.1073/pnas.1518830113","year":"2016","publication":"PNAS","day":"19","oa":1,"publisher":"National Academy of Sciences","quality_controlled":"1"},{"quality_controlled":"1","publisher":"Oxford University Press","oa":1,"has_accepted_license":"1","year":"2016","day":"01","publication":"Molecular Biology and Evolution","page":"761 - 769","date_published":"2016-03-01T00:00:00Z","doi":"10.1093/molbev/msv269","date_created":"2018-12-11T11:51:57Z","project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"citation":{"ieee":"M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic interactions in the arabinose cis-regulatory element,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016.","short":"M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769.","ama":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 2016;33(3):761-769. doi:10.1093/molbev/msv269","apa":"Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016). Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269","mla":"Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269.","ista":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3), 761–769.","chicago":"Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia","full_name":"Igler, Claudia","last_name":"Igler"},{"full_name":"Moreno, Anaisa","last_name":"Moreno","first_name":"Anaisa"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","last_name":"Bollback"}],"publist_id":"5772","title":"Epistatic interactions in the arabinose cis-regulatory element","abstract":[{"lang":"eng","text":"Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner."}],"oa_version":"Published Version","scopus_import":1,"month":"03","intvolume":" 33","publication_status":"published","file":[{"checksum":"1f456ce1d2aa2f67176a1709f9702ecf","file_id":"4751","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2018-12-12T10:09:27Z","file_name":"IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf","date_updated":"2020-07-14T12:44:53Z","file_size":648115,"creator":"system"}],"language":[{"iso":"eng"}],"issue":"3","volume":33,"ec_funded":1,"_id":"1427","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","pubrep_id":"588","date_updated":"2021-01-12T06:50:39Z","ddc":["570","576"],"file_date_updated":"2020-07-14T12:44:53Z","department":[{"_id":"CaGu"},{"_id":"JoBo"}]},{"status":"public","conference":{"name":"HSB: Hybrid Systems Biology","end_date":"2015-09-05","location":"Madrid, Spain","start_date":"2015-09-04"},"type":"conference","_id":"1524","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"date_updated":"2021-01-12T06:51:22Z","intvolume":" 9271","month":"01","main_file_link":[{"url":"http://arxiv.org/abs/1501.00440","open_access":"1"}],"alternative_title":["LNCS"],"scopus_import":1,"oa_version":"Preprint","abstract":[{"text":"When designing genetic circuits, the typical primitives used in major existing modelling formalisms are gene interaction graphs, where edges between genes denote either an activation or inhibition relation. However, when designing experiments, it is important to be precise about the low-level mechanistic details as to how each such relation is implemented. The rule-based modelling language Kappa allows to unambiguously specify mechanistic details such as DNA binding sites, dimerisation of transcription factors, or co-operative interactions. Such a detailed description comes with complexity and computationally costly executions. We propose a general method for automatically transforming a rule-based program, by eliminating intermediate species and adjusting the rate constants accordingly. To the best of our knowledge, we show the first automated reduction of rule-based models based on equilibrium approximations.\r\nOur algorithm is an adaptation of an existing algorithm, which was designed for reducing reaction-based programs; our version of the algorithm scans the rule-based Kappa model in search for those interaction patterns known to be amenable to equilibrium approximations (e.g. Michaelis-Menten scheme). Additional checks are then performed in order to verify if the reduction is meaningful in the context of the full model. The reduced model is efficiently obtained by static inspection over the rule-set. The tool is tested on a detailed rule-based model of a λ-phage switch, which lists 92 rules and 13 agents. The reduced model has 11 rules and 5 agents, and provides a dramatic reduction in simulation time of several orders of magnitude.","lang":"eng"}],"ec_funded":1,"volume":9271,"language":[{"iso":"eng"}],"publication_status":"published","project":[{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"}],"title":"Efficient reduction of kappa models by static inspection of the rule-set","author":[{"full_name":"Beica, Andreea","last_name":"Beica","first_name":"Andreea"},{"orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tatjana","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","last_name":"Petrov","orcid":"0000-0002-9041-0905","full_name":"Petrov, Tatjana"}],"publist_id":"5649","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"apa":"Beica, A., Guet, C. C., & Petrov, T. (2016). Efficient reduction of kappa models by static inspection of the rule-set (Vol. 9271, pp. 173–191). Presented at the HSB: Hybrid Systems Biology, Madrid, Spain: Springer. https://doi.org/10.1007/978-3-319-26916-0_10","ama":"Beica A, Guet CC, Petrov T. Efficient reduction of kappa models by static inspection of the rule-set. In: Vol 9271. Springer; 2016:173-191. doi:10.1007/978-3-319-26916-0_10","short":"A. Beica, C.C. Guet, T. Petrov, in:, Springer, 2016, pp. 173–191.","ieee":"A. Beica, C. C. Guet, and T. Petrov, “Efficient reduction of kappa models by static inspection of the rule-set,” presented at the HSB: Hybrid Systems Biology, Madrid, Spain, 2016, vol. 9271, pp. 173–191.","mla":"Beica, Andreea, et al. Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set. Vol. 9271, Springer, 2016, pp. 173–91, doi:10.1007/978-3-319-26916-0_10.","ista":"Beica A, Guet CC, Petrov T. 2016. Efficient reduction of kappa models by static inspection of the rule-set. HSB: Hybrid Systems Biology, LNCS, vol. 9271, 173–191.","chicago":"Beica, Andreea, Calin C Guet, and Tatjana Petrov. “Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set,” 9271:173–91. Springer, 2016. https://doi.org/10.1007/978-3-319-26916-0_10."},"oa":1,"quality_controlled":"1","publisher":"Springer","acknowledgement":"This research was supported by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291734, and the SNSF Early Postdoc.Mobility Fellowship, the grant number P2EZP2_148797.","date_created":"2018-12-11T11:52:31Z","doi":"10.1007/978-3-319-26916-0_10","date_published":"2016-01-10T00:00:00Z","page":"173 - 191","day":"10","year":"2016"},{"oa":1,"quality_controlled":"1","publisher":"Public Library of Science","acknowledgement":"This manuscript is dedicated to the memory of Alex Böhm, who was a great friend and a passionate biologist. Alex passed away after the initial submission of this manuscript. We thank Vesna Olivera and Ursula Sauder from the Zentrum für Mikroskopie Uni Basel for excellent service, and Olin Silander, Nikki Freed, and Nela Nikolic for helpful discussions. This work was supported by the Swiss National Science Foundation grants to M. Ackermann and Urs Jenal (supporting AB).","date_created":"2018-12-11T11:50:56Z","doi":"10.1371/journal.pgen.1005974","date_published":"2016-04-19T00:00:00Z","publication":"PLoS Genetics","day":"19","year":"2016","has_accepted_license":"1","article_number":"e1005974","title":"Genetic manipulation of glycogen allocation affects replicative lifespan in E coli","author":[{"full_name":"Boehm, Alex","last_name":"Boehm","first_name":"Alex"},{"first_name":"Markus","last_name":"Arnoldini","full_name":"Arnoldini, Markus"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","first_name":"Tobias","last_name":"Bergmiller","full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346"},{"first_name":"Thomas","last_name":"Röösli","full_name":"Röösli, Thomas"},{"full_name":"Bigosch, Colette","last_name":"Bigosch","first_name":"Colette"},{"last_name":"Ackermann","full_name":"Ackermann, Martin","first_name":"Martin"}],"publist_id":"6077","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"short":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, PLoS Genetics 12 (2016).","ieee":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Genetic manipulation of glycogen allocation affects replicative lifespan in E coli,” PLoS Genetics, vol. 12, no. 4. Public Library of Science, 2016.","ama":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 2016;12(4). doi:10.1371/journal.pgen.1005974","apa":"Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974","mla":"Boehm, Alex, et al. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics, vol. 12, no. 4, e1005974, Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974.","ista":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 12(4), e1005974.","chicago":"Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics. Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974."},"intvolume":" 12","month":"04","scopus_import":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles. We found that certain changes in the regulation of the carbohydrate metabolism can affect aging. A mutation in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative lifespan; csrA mutants stop dividing once their pole exceeds an age of about five divisions. These old-pole cells accumulate glycogen at their old cell poles; after their last division, they do not contain a chromosome, presumably because of spatial exclusion by the glycogen aggregates. The new-pole daughters produced by these aging mothers are born young; they only express the deleterious phenotype once their pole is old. These results demonstrate how manipulations of nutrient allocation can lead to the exclusion of the chromosome and limit replicative lifespan in E. coli, and illustrate how mutations can have phenotypic effects that are specific for cells with old poles. This raises the question how bacteria can avoid the accumulation of such mutations in their genomes over evolutionary times, and how they can achieve the long replicative lifespans that have recently been reported."}],"issue":"4","related_material":{"record":[{"relation":"research_data","status":"public","id":"9873"}]},"volume":12,"language":[{"iso":"eng"}],"file":[{"checksum":"53d22b2b39e5adc243d34f18b2615a85","file_id":"5067","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"IST-2016-705-v1+1_journal.pgen.1005974.PDF","date_created":"2018-12-12T10:14:17Z","file_size":6273249,"date_updated":"2020-07-14T12:44:41Z","creator":"system"}],"publication_status":"published","pubrep_id":"705","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","_id":"1250","department":[{"_id":"CaGu"}],"file_date_updated":"2020-07-14T12:44:41Z","ddc":["576","579"],"date_updated":"2023-02-23T14:11:39Z"},{"year":"2016","day":"19","related_material":{"record":[{"status":"public","id":"1250","relation":"used_in_publication"}]},"doi":"10.1371/journal.pgen.1005974.s015","date_created":"2021-08-10T09:42:34Z","oa_version":"Published Version","publisher":"Public Library of Science","month":"04","citation":{"mla":"Boehm, Alex, et al. Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality. Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974.s015.","apa":"Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Quantification of the growth rate reduction as a consequence of age-specific mortality. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974.s015","ama":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Quantification of the growth rate reduction as a consequence of age-specific mortality. 2016. doi:10.1371/journal.pgen.1005974.s015","short":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, (2016).","ieee":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Quantification of the growth rate reduction as a consequence of age-specific mortality.” Public Library of Science, 2016.","chicago":"Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality.” Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974.s015.","ista":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Quantification of the growth rate reduction as a consequence of age-specific mortality, Public Library of Science, 10.1371/journal.pgen.1005974.s015."},"date_updated":"2023-02-21T16:50:13Z","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","author":[{"first_name":"Alex","full_name":"Boehm, Alex","last_name":"Boehm"},{"last_name":"Arnoldini","full_name":"Arnoldini, Markus","first_name":"Markus"},{"first_name":"Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","last_name":"Bergmiller"},{"first_name":"Thomas","last_name":"Röösli","full_name":"Röösli, Thomas"},{"first_name":"Colette","last_name":"Bigosch","full_name":"Bigosch, Colette"},{"first_name":"Martin","last_name":"Ackermann","full_name":"Ackermann, Martin"}],"article_processing_charge":"No","department":[{"_id":"CaGu"}],"title":"Quantification of the growth rate reduction as a consequence of age-specific mortality","_id":"9873","type":"research_data_reference","status":"public"}]