--- _id: '820' abstract: - lang: eng text: "The lac operon is a classic model system for bacterial gene regulation, and has been studied extensively in E. coli, a classic model organism. However, not much is known about E. coli’s ecology and life outside the laboratory, in particular in soil and water environments. The natural diversity of the lac operon outside the laboratory, its role in the ecology of E. coli and the selection pressures it is exposed to, are similarly unknown.\r\nIn Chapter Two of this thesis, I explore the genetic diversity, phylogenetic history and signatures of selection of the lac operon across 20 natural isolates of E. coli and divergent clades of Escherichia. I found that complete lac operons were present in all isolates examined, which in all but one case were functional. The lac operon phylogeny conformed to the whole-genome phylogeny of the divergent Escherichia clades, which excludes horizontal gene transfer as an explanation for the presence of functional lac operons in these clades. All lac operon genes showed a signature of purifying selection; this signature was strongest for the lacY gene. Lac operon genes of human and environmental isolates showed similar signatures of selection, except the lacZ gene, which showed a stronger signature of selection in environmental isolates.\r\nIn Chapter Three, I try to identify the natural genetic variation relevant for phenotype and fitness in the lac operon, comparing growth rate on lactose and LacZ activity of the lac operons of these wild isolates in a common genetic background. Sequence variation in the lac promoter region, upstream of the -10 and -35 RNA polymerase binding motif, predicted variation in LacZ activity at full induction, using a thermodynamic model of polymerase binding (Tugrul, 2016). However, neither variation in LacZ activity, nor RNA polymerase binding predicted by the model correlated with variation in growth rate. Lac operons of human and environmental isolates did not differ systematically in either growth rate on lactose or LacZ protein activity, suggesting that these lac operons have been exposed to similar selection pressures. We thus have no evidence that the phenotypic variation we measured is relevant for fitness.\r\nTo start assessing the effect of genomic background on the growth phenotype conferred by the lac operon, I compared growth on minimal medium with lactose between lac operon constructs and the corresponding original isolates, I found that maximal growth rate was determined by genomic background, with almost all backgrounds conferring higher growth rates than lab strain K12 MG1655. However, I found no evidence that the lactose concentration at which growth was half maximal depended on genomic background." acknowledgement: "ERC H2020 programme (grant agreement no. 648440)\r\nThanks to Jon Bollback for giving me the chance to do this work, for sharing the ideas that lay at the basis of this work, for his honesty and openness, showing himself to me as a person and not just as a boss. Thanks to Nick Barton for his guidance at the last stage, reading and commenting extensively on several versions of this manuscript, and for his encouragement; thanks to both Jon and Nick for their kindness and patience. Thanks to Erik van Nimwegen and Calin Guet for their time and willingness to be in my thesis committee, and to Erik van Nimwegen especially for agreeing to enter my thesis committee at the last moment, and for his very sharp, helpful and relevant comments during and after the defense. Thanks to my collaborators and discussion partners: Anne Kupczok, for her guidance, ideas and discussions during the construction of the manuscript of Chapter Two, and her comments on the manuscript; Georg Rieckh for making me aware of the issue of parameter identifiability, suggesting how to solve it, and for his unfortunate idea to start the plasmid enterprise in the first place; Murat Tugrul for sharing his model, for his enthusiasm, and his comments on Chapter Three; Srdjan Sarikas for his collaboration on the Monod model fitting, fast forwarding the analysis to turbo speed and making beautiful figures, and making the discussion fun on top of it all; Vanessa Barone for her last minute comments, especially on Chapter Three, providing a sharp and very helpful experimentalist perspective at the last moment; Maros Pleska and Marjon de Vos for their comments on the manuscript of Chapter Two; Gasper Tkacik for his crucial input on the relation between growth rate and lactose concentration; Bor Kavcic for his input on growth rate modeling and error propagation. Thanks to the Bollback, Bollenbach, Barton, Guet and Tkacik group members for both pro- viding an inspiring and supportive scientific environment to work in, as well as a lot of warmth and colour to everyday life. And thanks to the friends I found here, to the people who were there for me and to the people who changed my life, making it stranger and more beautiful than I could have imagined, Maros, Vanessa, Tade, Suzi, Andrej, Peter, Tiago, Kristof, Karin, Irene, Misha, Mato, Guillaume and Zanin. " alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Fabienne full_name: Jesse, Fabienne id: 4C8C26A4-F248-11E8-B48F-1D18A9856A87 last_name: Jesse citation: ama: Jesse F. The lac operon in the wild. 2017. doi:10.15479/AT:ISTA:th_857 apa: Jesse, F. (2017). The lac operon in the wild. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_857 chicago: Jesse, Fabienne. “The Lac Operon in the Wild.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:th_857. ieee: F. Jesse, “The lac operon in the wild,” Institute of Science and Technology Austria, 2017. ista: Jesse F. 2017. The lac operon in the wild. Institute of Science and Technology Austria. mla: Jesse, Fabienne. The Lac Operon in the Wild. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:th_857. short: F. Jesse, The Lac Operon in the Wild, Institute of Science and Technology Austria, 2017. date_created: 2018-12-11T11:48:41Z date_published: 2017-08-25T00:00:00Z date_updated: 2023-09-07T12:01:21Z day: '25' ddc: - '576' - '577' - '579' degree_awarded: PhD department: - _id: JoBo doi: 10.15479/AT:ISTA:th_857 ec_funded: 1 file: - access_level: open_access checksum: c62257a7bff0c5f39e1abffc6bfcca5c content_type: application/pdf creator: system date_created: 2018-12-12T10:17:00Z date_updated: 2020-07-14T12:48:10Z file_id: '5252' file_name: IST-2017-857-v1+1_thesis_fabienne.pdf file_size: 3417773 relation: main_file - access_level: closed checksum: fc87d7d72fce52824a3ae7dcad0413a8 content_type: application/x-tex creator: dernst date_created: 2019-04-05T08:51:59Z date_updated: 2020-07-14T12:48:10Z file_id: '6212' file_name: 2017_thesis_Jesse_source.tex file_size: 215899 relation: source_file file_date_updated: 2020-07-14T12:48:10Z has_accepted_license: '1' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: '87' project: - _id: 2578D616-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '648440' name: Selective Barriers to Horizontal Gene Transfer publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '6829' pubrep_id: '857' status: public supervisor: - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 title: The lac operon in the wild tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2017' ... --- _id: '1077' abstract: - lang: eng text: Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the fX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima. article_number: '20160139' article_processing_charge: Yes (in subscription journal) author: - first_name: Rodrigo A full_name: Fernandes Redondo, Rodrigo A id: 409D5C96-F248-11E8-B48F-1D18A9856A87 last_name: Fernandes Redondo orcid: 0000-0002-5837-2793 - first_name: Harold full_name: Vladar, Harold id: 2A181218-F248-11E8-B48F-1D18A9856A87 last_name: Vladar orcid: 0000-0002-5985-7653 - first_name: Tomasz full_name: Włodarski, Tomasz last_name: Włodarski - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 citation: ama: Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. Journal of the Royal Society Interface. 2017;14(126). doi:10.1098/rsif.2016.0139 apa: Fernandes Redondo, R. A., de Vladar, H., Włodarski, T., & Bollback, J. P. (2017). Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. Journal of the Royal Society Interface. Royal Society of London. https://doi.org/10.1098/rsif.2016.0139 chicago: Fernandes Redondo, Rodrigo A, Harold de Vladar, Tomasz Włodarski, and Jonathan P Bollback. “Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family.” Journal of the Royal Society Interface. Royal Society of London, 2017. https://doi.org/10.1098/rsif.2016.0139. ieee: R. A. Fernandes Redondo, H. de Vladar, T. Włodarski, and J. P. Bollback, “Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family,” Journal of the Royal Society Interface, vol. 14, no. 126. Royal Society of London, 2017. ista: Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. 2017. Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. Journal of the Royal Society Interface. 14(126), 20160139. mla: Fernandes Redondo, Rodrigo A., et al. “Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family.” Journal of the Royal Society Interface, vol. 14, no. 126, 20160139, Royal Society of London, 2017, doi:10.1098/rsif.2016.0139. short: R.A. Fernandes Redondo, H. de Vladar, T. Włodarski, J.P. Bollback, Journal of the Royal Society Interface 14 (2017). date_created: 2018-12-11T11:50:01Z date_published: 2017-01-04T00:00:00Z date_updated: 2023-09-20T11:56:34Z day: '04' ddc: - '570' department: - _id: NiBa - _id: JoBo doi: 10.1098/rsif.2016.0139 ec_funded: 1 external_id: isi: - '000393380400001' file: - access_level: open_access content_type: application/pdf creator: dernst date_created: 2019-01-18T09:14:02Z date_updated: 2019-01-18T09:14:02Z file_id: '5843' file_name: 2017_JRSI_Redondo.pdf file_size: 1092015 relation: main_file success: 1 file_date_updated: 2019-01-18T09:14:02Z has_accepted_license: '1' intvolume: ' 14' isi: 1 issue: '126' language: - iso: eng month: '01' oa: 1 oa_version: Published Version project: - _id: 25B07788-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '250152' name: Limits to selection in biology and in evolutionary computation - _id: 2578D616-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '648440' name: Selective Barriers to Horizontal Gene Transfer publication: Journal of the Royal Society Interface publication_identifier: issn: - '17425689' publication_status: published publisher: Royal Society of London publist_id: '6303' quality_controlled: '1' related_material: record: - id: '9864' relation: research_data status: public scopus_import: '1' status: public title: Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 14 year: '2017' ... --- _id: '954' abstract: - lang: eng text: Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for. article_number: e25192 article_processing_charge: Yes author: - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 2017;6. doi:10.7554/eLife.25192 apa: Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192 chicago: Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192. ieee: M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the mechanistic nature of epistasis in a canonical cis-regulatory element,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192. mla: Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife, vol. 6, e25192, eLife Sciences Publications, 2017, doi:10.7554/eLife.25192. short: M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017). date_created: 2018-12-11T11:49:23Z date_published: 2017-05-18T00:00:00Z date_updated: 2023-09-22T10:01:17Z day: '18' ddc: - '576' department: - _id: CaGu - _id: NiBa - _id: JoBo doi: 10.7554/eLife.25192 ec_funded: 1 external_id: isi: - '000404024800001' file: - access_level: open_access checksum: 59cdd4400fb41280122d414fea971546 content_type: application/pdf creator: system date_created: 2018-12-12T10:17:49Z date_updated: 2020-07-14T12:48:16Z file_id: '5306' file_name: IST-2017-841-v1+1_elife-25192-v2.pdf file_size: 2441529 relation: main_file - access_level: open_access checksum: b69024880558b858eb8c5d47a92b6377 content_type: application/pdf creator: system date_created: 2018-12-12T10:17:50Z date_updated: 2020-07-14T12:48:16Z file_id: '5307' file_name: IST-2017-841-v1+2_elife-25192-figures-v2.pdf file_size: 3752660 relation: main_file file_date_updated: 2020-07-14T12:48:16Z has_accepted_license: '1' intvolume: ' 6' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 25B1EC9E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '618091' name: Speed of Adaptation in Population Genetics and Evolutionary Computation - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 2578D616-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '648440' name: Selective Barriers to Horizontal Gene Transfer publication: eLife publication_identifier: issn: - 2050084X publication_status: published publisher: eLife Sciences Publications publist_id: '6460' pubrep_id: '841' quality_controlled: '1' scopus_import: '1' status: public title: On the mechanistic nature of epistasis in a canonical cis-regulatory element tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 6 year: '2017' ... --- _id: '1427' 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. author: - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator - first_name: Claudia full_name: Igler, Claudia id: 46613666-F248-11E8-B48F-1D18A9856A87 last_name: Igler - first_name: Anaisa full_name: Moreno, Anaisa last_name: Moreno - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 citation: 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 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. 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. 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. 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. short: M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769. date_created: 2018-12-11T11:51:57Z date_published: 2016-03-01T00:00:00Z date_updated: 2021-01-12T06:50:39Z day: '01' ddc: - '570' - '576' department: - _id: CaGu - _id: JoBo doi: 10.1093/molbev/msv269 ec_funded: 1 file: - access_level: open_access checksum: 1f456ce1d2aa2f67176a1709f9702ecf content_type: application/pdf creator: system date_created: 2018-12-12T10:09:27Z date_updated: 2020-07-14T12:44:53Z file_id: '4751' file_name: IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf file_size: 648115 relation: main_file file_date_updated: 2020-07-14T12:44:53Z has_accepted_license: '1' intvolume: ' 33' issue: '3' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 761 - 769 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Molecular Biology and Evolution publication_status: published publisher: Oxford University Press publist_id: '5772' pubrep_id: '588' quality_controlled: '1' scopus_import: 1 status: public title: Epistatic interactions in the arabinose cis-regulatory element tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 33 year: '2016' ... --- _id: '1121' abstract: - lang: eng text: "Horizontal gene transfer (HGT), the lateral acquisition of genes across existing species\r\nboundaries, is a major evolutionary force shaping microbial genomes that facilitates\r\nadaptation to new environments as well as resistance to antimicrobial drugs. As such,\r\nunderstanding the mechanisms and constraints that determine the outcomes of HGT\r\nevents is crucial to understand the dynamics of HGT and to design better strategies to\r\novercome the challenges that originate from it.\r\nFollowing the insertion and expression of a newly transferred gene, the success of an\r\nHGT event will depend on the fitness effect it has on the recipient (host) cell. Therefore,\r\npredicting the impact of HGT on the genetic composition of a population critically\r\ndepends on the distribution of fitness effects (DFE) of horizontally transferred genes.\r\nHowever, to date, we have little knowledge of the DFE of newly transferred genes, and\r\nhence little is known about the shape and scale of this distribution.\r\nIt is particularly important to better understand the selective barriers that determine\r\nthe fitness effects of newly transferred genes. In spite of substantial bioinformatics\r\nefforts to identify horizontally transferred genes and selective barriers, a systematic\r\nexperimental approach to elucidate the roles of different selective barriers in defining\r\nthe fate of a transfer event has largely been absent. Similarly, although the fact that\r\nenvironment might alter the fitness effect of a horizontally transferred gene may seem\r\nobvious, little attention has been given to it in a systematic experimental manner.\r\nIn this study, we developed a systematic experimental approach that consists of\r\ntransferring 44 arbitrarily selected Salmonella typhimurium orthologous genes into an\r\nEscherichia coli host, and estimating the fitness effects of these transferred genes at a\r\nconstant expression level by performing competition assays against the wild type.\r\nIn chapter 2, we performed one-to-one competition assays between a mutant strain\r\ncarrying a transferred gene and the wild type strain. By using flow cytometry we\r\nestimated selection coefficients for the transferred genes with a precision level of 10-3,and obtained the DFE of horizontally transferred genes. We then investigated if these\r\nfitness effects could be predicted by any of the intrinsic properties of the genes, namely,\r\nfunctional category, degree of complexity (protein-protein interactions), GC content,\r\ncodon usage and length. Our analyses revealed that the functional category and length\r\nof the genes act as potential selective barriers. Finally, using the same procedure with\r\nthe endogenous E. coli orthologs of these 44 genes, we demonstrated that gene dosage is\r\nthe most prominent selective barrier to HGT.\r\nIn chapter 3, using the same set of genes we investigated the role of environment on the\r\nsuccess of HGT events. Under six different environments with different levels of stress\r\nwe performed more complex competition assays, where we mixed all 44 mutant strains\r\ncarrying transferred genes with the wild type strain. To estimate the fitness effects of\r\ngenes relative to wild type we used next generation sequencing. We found that the DFEs\r\nof horizontally transferred genes are highly dependent on the environment, with\r\nabundant gene–by-environment interactions. Furthermore, we demonstrated a\r\nrelationship between average fitness effect of a gene across all environments and its\r\nenvironmental variance, and thus its predictability. Finally, in spite of the fitness effects\r\nof genes being highly environment-dependent, we still observed a common shape of\r\nDFEs across all tested environments." acknowledgement: "This study was supported by European Research Council ERC CoG 2014 – EVOLHGT,\r\nunder the grant number 648440.\r\n\r\nIt is a pleasure to thank the many people who made this thesis possible.\r\nI would like to first thank my advisor, Jonathan Paul Bollback for providing guidance in\r\nall aspects of my life, encouragement, sound advice, and good teaching over the last six\r\nyears.\r\nI would also like to thank the members of my dissertation committee – Călin C. Guet\r\nand John F. Baines – not only for their time and guidance, but for their intellectual\r\ncontributions to my development as a scientist.\r\nI would like to thank Flavia Gama and Rodrigo Redondo who have taught me all the\r\nskills in the laboratory with their graciousness and friendship. Also special thanks to\r\nBollback group for their support and for providing a stimulating and fun environment:\r\nIsabella Tomanek, Fabienne Jesse, Claudia Igler, and Pavel Payne.\r\nJerneja Beslagic is not only an amazing assistant, she also has a smile brighter and\r\nwarmer than the sunshine, bringing happiness to every moment. Always keep your light\r\nNeja, I will miss our invaluable chatters a lot." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Hande full_name: Acar, Hande id: 2DDF136A-F248-11E8-B48F-1D18A9856A87 last_name: Acar orcid: 0000-0003-1986-9753 citation: ama: Acar H. Selective barriers to horizontal gene transfer. 2016. apa: Acar, H. (2016). Selective barriers to horizontal gene transfer. Institute of Science and Technology Austria. chicago: Acar, Hande. “Selective Barriers to Horizontal Gene Transfer.” Institute of Science and Technology Austria, 2016. ieee: H. Acar, “Selective barriers to horizontal gene transfer,” Institute of Science and Technology Austria, 2016. ista: Acar H. 2016. Selective barriers to horizontal gene transfer. Institute of Science and Technology Austria. mla: Acar, Hande. Selective Barriers to Horizontal Gene Transfer. Institute of Science and Technology Austria, 2016. short: H. Acar, Selective Barriers to Horizontal Gene Transfer, Institute of Science and Technology Austria, 2016. date_created: 2018-12-11T11:50:16Z date_published: 2016-12-01T00:00:00Z date_updated: 2023-09-07T11:42:26Z day: '01' ddc: - '570' degree_awarded: PhD department: - _id: JoBo ec_funded: 1 file: - access_level: closed checksum: 94bbbc754c36115bf37f8fc11fad43c4 content_type: application/pdf creator: dernst date_created: 2019-08-13T11:17:50Z date_updated: 2019-08-13T11:17:50Z file_id: '6814' file_name: PhDThesis_HandeAcar_1230.pdf file_size: 3682711 relation: main_file - access_level: open_access checksum: 94bbbc754c36115bf37f8fc11fad43c4 content_type: application/pdf creator: dernst date_created: 2021-02-22T11:51:13Z date_updated: 2021-02-22T11:51:13Z file_id: '9184' file_name: 2016_Thesis_HandeAcar.pdf file_size: 3682711 relation: main_file success: 1 file_date_updated: 2021-02-22T11:51:13Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '75' project: - _id: 2578D616-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '648440' name: Selective Barriers to Horizontal Gene Transfer publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '6239' status: public supervisor: - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 title: Selective barriers to horizontal gene transfer type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2016' ... --- _id: '9864' abstract: - lang: eng text: Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by, first, reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima. article_processing_charge: No author: - first_name: Rodrigo A full_name: Fernandes Redondo, Rodrigo A id: 409D5C96-F248-11E8-B48F-1D18A9856A87 last_name: Fernandes Redondo orcid: 0000-0002-5837-2793 - first_name: Harold full_name: de Vladar, Harold id: 2A181218-F248-11E8-B48F-1D18A9856A87 last_name: de Vladar orcid: 0000-0002-5985-7653 - first_name: Tomasz full_name: Włodarski, Tomasz last_name: Włodarski - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 citation: ama: Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. 2016. doi:10.6084/m9.figshare.4315652.v1 apa: Fernandes Redondo, R. A., de Vladar, H., Włodarski, T., & Bollback, J. P. (2016). Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. The Royal Society. https://doi.org/10.6084/m9.figshare.4315652.v1 chicago: Fernandes Redondo, Rodrigo A, Harold de Vladar, Tomasz Włodarski, and Jonathan P Bollback. “Data from Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family.” The Royal Society, 2016. https://doi.org/10.6084/m9.figshare.4315652.v1. ieee: R. A. Fernandes Redondo, H. de Vladar, T. Włodarski, and J. P. Bollback, “Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family.” The Royal Society, 2016. ista: Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. 2016. Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family, The Royal Society, 10.6084/m9.figshare.4315652.v1. mla: Fernandes Redondo, Rodrigo A., et al. Data from Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family. The Royal Society, 2016, doi:10.6084/m9.figshare.4315652.v1. short: R.A. Fernandes Redondo, H. de Vladar, T. Włodarski, J.P. Bollback, (2016). date_created: 2021-08-10T08:29:47Z date_published: 2016-12-14T00:00:00Z date_updated: 2023-09-20T11:56:33Z day: '14' department: - _id: NiBa - _id: JoBo doi: 10.6084/m9.figshare.4315652.v1 main_file_link: - open_access: '1' url: https://doi.org/10.6084/m9.figshare.4315652.v1 month: '12' oa: 1 oa_version: Published Version publisher: The Royal Society related_material: record: - id: '1077' relation: used_in_publication status: public status: public title: Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2016' ... --- _id: '5554' abstract: - lang: eng text: "The data stored here is used in Murat Tugrul's PhD thesis (Chapter 3), which is related to the evolution of bacterial RNA polymerase binding.\r\nMagdalena Steinrueck (PhD Student in Calin Guet's group at IST Austria) performed the experiments and created the data on de novo promoter evolution. Fabienne Jesse (PhD Student in Jon Bollback's group at IST Austria) performed the experiments and created the data on lac promoter evolution." article_processing_charge: No author: - first_name: Murat full_name: Tugrul, Murat id: 37C323C6-F248-11E8-B48F-1D18A9856A87 last_name: Tugrul orcid: 0000-0002-8523-0758 citation: ama: Tugrul M. Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase. 2016. doi:10.15479/AT:ISTA:43 apa: Tugrul, M. (2016). Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:43 chicago: Tugrul, Murat. “Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase.” Institute of Science and Technology Austria, 2016. https://doi.org/10.15479/AT:ISTA:43. ieee: M. Tugrul, “Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase.” Institute of Science and Technology Austria, 2016. ista: Tugrul M. 2016. Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase, Institute of Science and Technology Austria, 10.15479/AT:ISTA:43. mla: Tugrul, Murat. Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase. Institute of Science and Technology Austria, 2016, doi:10.15479/AT:ISTA:43. short: M. Tugrul, (2016). contributor: - contributor_type: researcher first_name: Magdalena id: 2C023F40-F248-11E8-B48F-1D18A9856A87 last_name: Steinrück - contributor_type: researcher first_name: Fabienne id: 4C8C26A4-F248-11E8-B48F-1D18A9856A87 last_name: Jesse datarep_id: '43' date_created: 2018-12-12T12:31:30Z date_published: 2016-05-12T00:00:00Z date_updated: 2024-02-21T13:50:34Z day: '12' department: - _id: NiBa - _id: JoBo doi: 10.15479/AT:ISTA:43 file: - access_level: open_access checksum: 1fc0a10bb7ce110fcb5e1fbe3cf0c4e2 content_type: application/zip creator: system date_created: 2018-12-12T13:03:08Z date_updated: 2020-07-14T12:47:01Z file_id: '5626' file_name: IST-2016-43-v1+1_DATA_MTugrul_PhDThesis_Chapter3.zip file_size: 1123495 relation: main_file file_date_updated: 2020-07-14T12:47:01Z has_accepted_license: '1' keyword: - RNAP binding - de novo promoter evolution - lac promoter license: https://creativecommons.org/publicdomain/zero/1.0/ month: '05' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '1131' relation: used_in_publication status: public status: public title: Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase tmp: image: /images/cc_0.png legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode name: Creative Commons Public Domain Dedication (CC0 1.0) short: CC0 (1.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2016' ... --- _id: '1902' abstract: - lang: eng text: In the 1960s-1980s, determination of bacterial growth rates was an important tool in microbial genetics, biochemistry, molecular biology, and microbial physiology. The exciting technical developments of the 1990s and the 2000s eclipsed that tool; as a result, many investigators today lack experience with growth rate measurements. Recently, investigators in a number of areas have started to use measurements of bacterial growth rates for a variety of purposes. Those measurements have been greatly facilitated by the availability of microwell plate readers that permit the simultaneous measurements on up to 384 different cultures. Only the exponential (logarithmic) portions of the resulting growth curves are useful for determining growth rates, and manual determination of that portion and calculation of growth rates can be tedious for high-throughput purposes. Here, we introduce the program GrowthRates that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase. GrowthRates is freely available for Macintosh, Windows, and Linux.We discuss the effects of culture volume, the classical bacterial growth curve, and the differences between determinations in rich media and minimal (mineral salts) media. This protocol covers calibration of the plate reader, growth of culture inocula for both rich and minimal media, and experimental setup. As a guide to reliability, we report typical day-to-day variation in growth rates and variation within experiments with respect to position of wells within the plates. article_processing_charge: No article_type: original author: - first_name: Barry full_name: Hall, Barry last_name: Hall - first_name: Hande full_name: Acar, Hande id: 2DDF136A-F248-11E8-B48F-1D18A9856A87 last_name: Acar orcid: 0000-0003-1986-9753 - first_name: Anna full_name: Nandipati, Anna last_name: Nandipati - first_name: Miriam full_name: Barlow, Miriam last_name: Barlow citation: ama: Hall B, Acar H, Nandipati A, Barlow M. Growth rates made easy. Molecular Biology and Evolution. 2014;31(1):232-238. doi:10.1093/molbev/mst187 apa: Hall, B., Acar, H., Nandipati, A., & Barlow, M. (2014). Growth rates made easy. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/mst187 chicago: Hall, Barry, Hande Acar, Anna Nandipati, and Miriam Barlow. “Growth Rates Made Easy.” Molecular Biology and Evolution. Oxford University Press, 2014. https://doi.org/10.1093/molbev/mst187. ieee: B. Hall, H. Acar, A. Nandipati, and M. Barlow, “Growth rates made easy,” Molecular Biology and Evolution, vol. 31, no. 1. Oxford University Press, pp. 232–238, 2014. ista: Hall B, Acar H, Nandipati A, Barlow M. 2014. Growth rates made easy. Molecular Biology and Evolution. 31(1), 232–238. mla: Hall, Barry, et al. “Growth Rates Made Easy.” Molecular Biology and Evolution, vol. 31, no. 1, Oxford University Press, 2014, pp. 232–38, doi:10.1093/molbev/mst187. short: B. Hall, H. Acar, A. Nandipati, M. Barlow, Molecular Biology and Evolution 31 (2014) 232–238. date_created: 2018-12-11T11:54:37Z date_published: 2014-01-01T00:00:00Z date_updated: 2022-06-07T11:08:13Z day: '01' department: - _id: JoBo doi: 10.1093/molbev/mst187 external_id: pmid: - '24170494' intvolume: ' 31' issue: '1' language: - iso: eng month: '01' oa_version: None page: 232 - 238 pmid: 1 publication: Molecular Biology and Evolution publication_identifier: eissn: - 1537-1719 issn: - 0737-4038 publication_status: published publisher: Oxford University Press publist_id: '5193' quality_controlled: '1' scopus_import: '1' status: public title: Growth rates made easy type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 31 year: '2014' ... --- _id: '2042' abstract: - lang: eng text: 'Background: CRISPR is a microbial immune system likely to be involved in host-parasite coevolution. It functions using target sequences encoded by the bacterial genome, which interfere with invading nucleic acids using a homology-dependent system. The system also requires protospacer associated motifs (PAMs), short motifs close to the target sequence that are required for interference in CRISPR types I and II. Here, we investigate whether PAMs are depleted in phage genomes due to selection pressure to escape recognition.Results: To this end, we analyzed two data sets. Phages infecting all bacterial hosts were analyzed first, followed by a detailed analysis of phages infecting the genus Streptococcus, where PAMs are best understood. We use two different measures of motif underrepresentation that control for codon bias and the frequency of submotifs. We compare phages infecting species with a particular CRISPR type to those infecting species without that type. Since only known PAMs were investigated, the analysis is restricted to CRISPR types I-C and I-E and in Streptococcus to types I-C and II. We found evidence for PAM depletion in Streptococcus phages infecting hosts with CRISPR type I-C, in Vibrio phages infecting hosts with CRISPR type I-E and in Streptococcus thermopilus phages infecting hosts with type II-A, known as CRISPR3.Conclusions: The observed motif depletion in phages with hosts having CRISPR can be attributed to selection rather than to mutational bias, as mutational bias should affect the phages of all hosts. This observation implies that the CRISPR system has been efficient in the groups discussed here.' article_number: '663' author: - first_name: Anne full_name: Kupczok, Anne id: 2BB22BC2-F248-11E8-B48F-1D18A9856A87 last_name: Kupczok - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 citation: ama: Kupczok A, Bollback JP. Motif depletion in bacteriophages infecting hosts with CRISPR systems. BMC Genomics. 2014;15(1). doi:10.1186/1471-2164-15-663 apa: Kupczok, A., & Bollback, J. P. (2014). Motif depletion in bacteriophages infecting hosts with CRISPR systems. BMC Genomics. BioMed Central. https://doi.org/10.1186/1471-2164-15-663 chicago: Kupczok, Anne, and Jonathan P Bollback. “Motif Depletion in Bacteriophages Infecting Hosts with CRISPR Systems.” BMC Genomics. BioMed Central, 2014. https://doi.org/10.1186/1471-2164-15-663. ieee: A. Kupczok and J. P. Bollback, “Motif depletion in bacteriophages infecting hosts with CRISPR systems,” BMC Genomics, vol. 15, no. 1. BioMed Central, 2014. ista: Kupczok A, Bollback JP. 2014. Motif depletion in bacteriophages infecting hosts with CRISPR systems. BMC Genomics. 15(1), 663. mla: Kupczok, Anne, and Jonathan P. Bollback. “Motif Depletion in Bacteriophages Infecting Hosts with CRISPR Systems.” BMC Genomics, vol. 15, no. 1, 663, BioMed Central, 2014, doi:10.1186/1471-2164-15-663. short: A. Kupczok, J.P. Bollback, BMC Genomics 15 (2014). date_created: 2018-12-11T11:55:23Z date_published: 2014-08-08T00:00:00Z date_updated: 2021-01-12T06:54:56Z day: '08' ddc: - '570' department: - _id: JoBo doi: 10.1186/1471-2164-15-663 file: - access_level: open_access checksum: 3f6d2776b90a842a28359cc957d3d04b content_type: application/pdf creator: system date_created: 2018-12-12T10:11:24Z date_updated: 2020-07-14T12:45:26Z file_id: '4878' file_name: IST-2015-396-v1+1_1471-2164-15-663.pdf file_size: 1489769 relation: main_file file_date_updated: 2020-07-14T12:45:26Z has_accepted_license: '1' intvolume: ' 15' issue: '1' language: - iso: eng month: '08' oa: 1 oa_version: Published Version publication: BMC Genomics publication_status: published publisher: BioMed Central publist_id: '5009' pubrep_id: '396' quality_controlled: '1' scopus_import: 1 status: public title: Motif depletion in bacteriophages infecting hosts with CRISPR systems tmp: image: /images/cc_0.png legal_code_url: https://creativecommons.org/publicdomain/zero/1.0/legalcode name: Creative Commons Public Domain Dedication (CC0 1.0) short: CC0 (1.0) type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 15 year: '2014' ... --- _id: '2412' abstract: - lang: eng text: 'Background: The CRISPR/Cas system is known to act as an adaptive and heritable immune system in Eubacteria and Archaea. Immunity is encoded in an array of spacer sequences. Each spacer can provide specific immunity to invasive elements that carry the same or a similar sequence. Even in closely related strains, spacer content is very dynamic and evolves quickly. Standard models of nucleotide evolutioncannot be applied to quantify its rate of change since processes other than single nucleotide changes determine its evolution.Methods We present probabilistic models that are specific for spacer content evolution. They account for the different processes of insertion and deletion. Insertions can be constrained to occur on one end only or are allowed to occur throughout the array. One deletion event can affect one spacer or a whole fragment of adjacent spacers. Parameters of the underlying models are estimated for a pair of arrays by maximum likelihood using explicit ancestor enumeration.Results Simulations show that parameters are well estimated on average under the models presented here. There is a bias in the rate estimation when including fragment deletions. The models also estimate times between pairs of strains. But with increasing time, spacer overlap goes to zero, and thus there is an upper bound on the distance that can be estimated. Spacer content similarities are displayed in a distance based phylogeny using the estimated times.We use the presented models to analyze different Yersinia pestis data sets and find that the results among them are largely congruent. The models also capture the variation in diversity of spacers among the data sets. A comparison of spacer-based phylogenies and Cas gene phylogenies shows that they resolve very different time scales for this data set.Conclusions The simulations and data analyses show that the presented models are useful for quantifying spacer content evolution and for displaying spacer content similarities of closely related strains in a phylogeny. This allows for comparisons of different CRISPR arrays or for comparisons between CRISPR arrays and nucleotide substitution rates.' author: - first_name: Anne full_name: Kupczok, Anne id: 2BB22BC2-F248-11E8-B48F-1D18A9856A87 last_name: Kupczok - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 citation: ama: Kupczok A, Bollback JP. Probabilistic models for CRISPR spacer content evolution . BMC Evolutionary Biology. 2013;13(1):54-54. doi:10.1186/1471-2148-13-54 apa: Kupczok, A., & Bollback, J. P. (2013). Probabilistic models for CRISPR spacer content evolution . BMC Evolutionary Biology. BioMed Central. https://doi.org/10.1186/1471-2148-13-54 chicago: Kupczok, Anne, and Jonathan P Bollback. “Probabilistic Models for CRISPR Spacer Content Evolution .” BMC Evolutionary Biology. BioMed Central, 2013. https://doi.org/10.1186/1471-2148-13-54. ieee: A. Kupczok and J. P. Bollback, “Probabilistic models for CRISPR spacer content evolution ,” BMC Evolutionary Biology, vol. 13, no. 1. BioMed Central, pp. 54–54, 2013. ista: Kupczok A, Bollback JP. 2013. Probabilistic models for CRISPR spacer content evolution . BMC Evolutionary Biology. 13(1), 54–54. mla: Kupczok, Anne, and Jonathan P. Bollback. “Probabilistic Models for CRISPR Spacer Content Evolution .” BMC Evolutionary Biology, vol. 13, no. 1, BioMed Central, 2013, pp. 54–54, doi:10.1186/1471-2148-13-54. short: A. Kupczok, J.P. Bollback, BMC Evolutionary Biology 13 (2013) 54–54. date_created: 2018-12-11T11:57:31Z date_published: 2013-02-26T00:00:00Z date_updated: 2021-01-12T06:57:20Z day: '26' ddc: - '576' department: - _id: JoBo doi: 10.1186/1471-2148-13-54 file: - access_level: open_access checksum: 029c7e0b198c19312b66ecce3cabb22f content_type: application/pdf creator: system date_created: 2018-12-12T10:17:15Z date_updated: 2020-07-14T12:45:40Z file_id: '5268' file_name: IST-2015-397-v1+1_1471-2148-13-54.pdf file_size: 518729 relation: main_file file_date_updated: 2020-07-14T12:45:40Z has_accepted_license: '1' intvolume: ' 13' issue: '1' language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: 54 - 54 publication: BMC Evolutionary Biology publication_status: published publisher: BioMed Central publist_id: '4514' pubrep_id: '397' quality_controlled: '1' scopus_import: 1 status: public title: 'Probabilistic models for CRISPR spacer content evolution ' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2013' ...