---
_id: '9840'
abstract:
- lang: eng
  text: Herd immunity, a process in which resistant individuals limit the spread of
    a pathogen among susceptible hosts has been extensively studied in eukaryotes.
    Even though bacteria have evolved multiple immune systems against their phage
    pathogens, herd immunity in bacteria remains unexplored. Here we experimentally
    demonstrate that herd immunity arises during phage epidemics in structured and
    unstructured Escherichia coli populations consisting of differing frequencies
    of susceptible and resistant cells harboring CRISPR immunity. In addition, we
    develop a mathematical model that quantifies how herd immunity is affected by
    spatial population structure, bacterial growth rate, and phage replication rate.
    Using our model we infer a general epidemiological rule describing the relative
    speed of an epidemic in partially resistant spatially structured populations.
    Our experimental and theoretical findings indicate that herd immunity may be important
    in bacterial communities, allowing for stable coexistence of bacteria and their
    phages and the maintenance of polymorphism in bacterial immunity.
article_processing_charge: No
author:
- first_name: Pavel
  full_name: Payne, Pavel
  id: 35F78294-F248-11E8-B48F-1D18A9856A87
  last_name: Payne
  orcid: 0000-0002-2711-9453
- first_name: Lukas
  full_name: Geyrhofer, Lukas
  last_name: Geyrhofer
- 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
citation:
  ama: 'Payne P, Geyrhofer L, Barton NH, Bollback JP. Data from: CRISPR-based herd
    immunity limits phage epidemics in bacterial populations. 2018. doi:<a href="https://doi.org/10.5061/dryad.42n44">10.5061/dryad.42n44</a>'
  apa: 'Payne, P., Geyrhofer, L., Barton, N. H., &#38; Bollback, J. P. (2018). Data
    from: CRISPR-based herd immunity limits phage epidemics in bacterial populations.
    Dryad. <a href="https://doi.org/10.5061/dryad.42n44">https://doi.org/10.5061/dryad.42n44</a>'
  chicago: 'Payne, Pavel, Lukas Geyrhofer, Nicholas H Barton, and Jonathan P Bollback.
    “Data from: CRISPR-Based Herd Immunity Limits Phage Epidemics in Bacterial Populations.”
    Dryad, 2018. <a href="https://doi.org/10.5061/dryad.42n44">https://doi.org/10.5061/dryad.42n44</a>.'
  ieee: 'P. Payne, L. Geyrhofer, N. H. Barton, and J. P. Bollback, “Data from: CRISPR-based
    herd immunity limits phage epidemics in bacterial populations.” Dryad, 2018.'
  ista: 'Payne P, Geyrhofer L, Barton NH, Bollback JP. 2018. Data from: CRISPR-based
    herd immunity limits phage epidemics in bacterial populations, Dryad, <a href="https://doi.org/10.5061/dryad.42n44">10.5061/dryad.42n44</a>.'
  mla: 'Payne, Pavel, et al. <i>Data from: CRISPR-Based Herd Immunity Limits Phage
    Epidemics in Bacterial Populations</i>. Dryad, 2018, doi:<a href="https://doi.org/10.5061/dryad.42n44">10.5061/dryad.42n44</a>.'
  short: P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, (2018).
date_created: 2021-08-09T13:10:02Z
date_published: 2018-03-12T00:00:00Z
date_updated: 2025-04-15T08:17:50Z
day: '12'
department:
- _id: NiBa
- _id: JoBo
doi: 10.5061/dryad.42n44
main_file_link:
- open_access: '1'
  url: https://doi.org/10.5061/dryad.42n44
month: '03'
oa: 1
oa_version: Published Version
publisher: Dryad
related_material:
  record:
  - id: '423'
    relation: used_in_publication
    status: public
status: public
title: 'Data from: CRISPR-based herd immunity limits phage epidemics in bacterial
  populations'
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2018'
...
---
_id: '423'
abstract:
- lang: eng
  text: Herd immunity, a process in which resistant individuals limit the spread of
    a pathogen among susceptible hosts has been extensively studied in eukaryotes.
    Even though bacteria have evolved multiple immune systems against their phage
    pathogens, herd immunity in bacteria remains unexplored. Here we experimentally
    demonstrate that herd immunity arises during phage epidemics in structured and
    unstructured Escherichia coli populations consisting of differing frequencies
    of susceptible and resistant cells harboring CRISPR immunity. In addition, we
    develop a mathematical model that quantifies how herd immunity is affected by
    spatial population structure, bacterial growth rate, and phage replication rate.
    Using our model we infer a general epidemiological rule describing the relative
    speed of an epidemic in partially resistant spatially structured populations.
    Our experimental and theoretical findings indicate that herd immunity may be important
    in bacterial communities, allowing for stable coexistence of bacteria and their
    phages and the maintenance of polymorphism in bacterial immunity.
acknowledgement: "We are grateful to Remy Chait for his help and assistance with establishing
  our experimental setups and to Tobias Bergmiller for valuable insights into some
  specific experimental details. We thank Luciano Marraffini for donating us the pCas9
  plasmid used in this study. We also want to express our gratitude to Seth Barribeau,
  Andrea Betancourt, Călin Guet, Mato Lagator, Tiago Paixão and Maroš Pleška for valuable
  discussions on the manuscript. Finally, we would like to thank the \r\neditors and
  reviewers for their helpful comments and suggestions."
article_number: e32035
article_processing_charge: No
author:
- first_name: Pavel
  full_name: Payne, Pavel
  id: 35F78294-F248-11E8-B48F-1D18A9856A87
  last_name: Payne
  orcid: 0000-0002-2711-9453
- first_name: Lukas
  full_name: Geyrhofer, Lukas
  last_name: Geyrhofer
- 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
citation:
  ama: Payne P, Geyrhofer L, Barton NH, Bollback JP. CRISPR-based herd immunity can
    limit phage epidemics in bacterial populations. <i>eLife</i>. 2018;7. doi:<a href="https://doi.org/10.7554/eLife.32035">10.7554/eLife.32035</a>
  apa: Payne, P., Geyrhofer, L., Barton, N. H., &#38; Bollback, J. P. (2018). CRISPR-based
    herd immunity can limit phage epidemics in bacterial populations. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.32035">https://doi.org/10.7554/eLife.32035</a>
  chicago: Payne, Pavel, Lukas Geyrhofer, Nicholas H Barton, and Jonathan P Bollback.
    “CRISPR-Based Herd Immunity Can Limit Phage Epidemics in Bacterial Populations.”
    <i>ELife</i>. eLife Sciences Publications, 2018. <a href="https://doi.org/10.7554/eLife.32035">https://doi.org/10.7554/eLife.32035</a>.
  ieee: P. Payne, L. Geyrhofer, N. H. Barton, and J. P. Bollback, “CRISPR-based herd
    immunity can limit phage epidemics in bacterial populations,” <i>eLife</i>, vol.
    7. eLife Sciences Publications, 2018.
  ista: Payne P, Geyrhofer L, Barton NH, Bollback JP. 2018. CRISPR-based herd immunity
    can limit phage epidemics in bacterial populations. eLife. 7, e32035.
  mla: Payne, Pavel, et al. “CRISPR-Based Herd Immunity Can Limit Phage Epidemics
    in Bacterial Populations.” <i>ELife</i>, vol. 7, e32035, eLife Sciences Publications,
    2018, doi:<a href="https://doi.org/10.7554/eLife.32035">10.7554/eLife.32035</a>.
  short: P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, ELife 7 (2018).
date_created: 2018-12-11T11:46:23Z
date_published: 2018-03-09T00:00:00Z
date_updated: 2025-03-31T16:00:24Z
day: '09'
ddc:
- '576'
department:
- _id: NiBa
- _id: JoBo
doi: 10.7554/eLife.32035
ec_funded: 1
external_id:
  isi:
  - '000431035800001'
file:
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  checksum: 447cf6e680bdc3c01062a8737d876569
  content_type: application/pdf
  creator: dernst
  date_created: 2018-12-17T10:36:07Z
  date_updated: 2020-07-14T12:46:25Z
  file_id: '5689'
  file_name: 2018_eLife_Payne.pdf
  file_size: 3533881
  relation: main_file
file_date_updated: 2020-07-14T12:46:25Z
has_accepted_license: '1'
intvolume: '         7'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 2578D616-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '648440'
  name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_status: published
publisher: eLife Sciences Publications
publist_id: '7400'
quality_controlled: '1'
related_material:
  record:
  - id: '9840'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: CRISPR-based herd immunity can limit phage epidemics in bacterial populations
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: 7
year: '2018'
...
---
_id: '67'
abstract:
- lang: eng
  text: 'Gene regulatory networks evolve through rewiring of individual components—that
    is, through changes in regulatory connections. However, the mechanistic basis
    of regulatory rewiring is poorly understood. Using a canonical gene regulatory
    system, we quantify the properties of transcription factors that determine the
    evolutionary potential for rewiring of regulatory connections: robustness, tunability
    and evolvability. In vivo repression measurements of two repressors at mutated
    operator sites reveal their contrasting evolutionary potential: while robustness
    and evolvability were positively correlated, both were in trade-off with tunability.
    Epistatic interactions between adjacent operators alleviated this trade-off. A
    thermodynamic model explains how the differences in robustness, tunability and
    evolvability arise from biophysical characteristics of repressor–DNA binding.
    The model also uncovers that the energy matrix, which describes how mutations
    affect repressor–DNA binding, encodes crucial information about the evolutionary
    potential of a repressor. The biophysical determinants of evolutionary potential
    for regulatory rewiring constitute a mechanistic framework for understanding network
    evolution.'
article_processing_charge: No
article_type: original
author:
- first_name: Claudia
  full_name: Igler, Claudia
  id: 46613666-F248-11E8-B48F-1D18A9856A87
  last_name: Igler
  orcid: 0000-0001-7777-546X
- first_name: Mato
  full_name: Lagator, Mato
  id: 345D25EC-F248-11E8-B48F-1D18A9856A87
  last_name: Lagator
- first_name: Gasper
  full_name: Tkacik, Gasper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkacik
  orcid: 0000-0002-6699-1455
- 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: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential
    of transcription factors for gene regulatory rewiring. <i>Nature Ecology and Evolution</i>.
    2018;2(10):1633-1643. doi:<a href="https://doi.org/10.1038/s41559-018-0651-y">10.1038/s41559-018-0651-y</a>
  apa: Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., &#38; Guet, C. C. (2018).
    Evolutionary potential of transcription factors for gene regulatory rewiring.
    <i>Nature Ecology and Evolution</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/s41559-018-0651-y">https://doi.org/10.1038/s41559-018-0651-y</a>
  chicago: Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin
    C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.”
    <i>Nature Ecology and Evolution</i>. Nature Publishing Group, 2018. <a href="https://doi.org/10.1038/s41559-018-0651-y">https://doi.org/10.1038/s41559-018-0651-y</a>.
  ieee: C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary
    potential of transcription factors for gene regulatory rewiring,” <i>Nature Ecology
    and Evolution</i>, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018.
  ista: Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential
    of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution.
    2(10), 1633–1643.
  mla: Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for
    Gene Regulatory Rewiring.” <i>Nature Ecology and Evolution</i>, vol. 2, no. 10,
    Nature Publishing Group, 2018, pp. 1633–43, doi:<a href="https://doi.org/10.1038/s41559-018-0651-y">10.1038/s41559-018-0651-y</a>.
  short: C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology
    and Evolution 2 (2018) 1633–1643.
date_created: 2018-12-11T11:44:27Z
date_published: 2018-09-10T00:00:00Z
date_updated: 2026-04-27T22:30:47Z
day: '10'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
- _id: JoBo
doi: 10.1038/s41559-018-0651-y
ec_funded: 1
external_id:
  isi:
  - '000447947600021'
file:
- access_level: open_access
  checksum: 383a2e2c944a856e2e821ec8e7bf71b6
  content_type: application/pdf
  creator: dernst
  date_created: 2020-05-14T11:28:52Z
  date_updated: 2020-07-14T12:47:37Z
  file_id: '7830'
  file_name: 2018_NatureEcology_Igler.pdf
  file_size: 1135973
  relation: main_file
file_date_updated: 2020-07-14T12:47:37Z
has_accepted_license: '1'
intvolume: '         2'
isi: 1
issue: '10'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Submitted Version
page: 1633 - 1643
project:
- _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
- _id: 251EE76E-B435-11E9-9278-68D0E5697425
  grant_number: '24573'
  name: Design principles underlying genetic switch architecture
publication: Nature Ecology and Evolution
publication_status: published
publisher: Nature Publishing Group
publist_id: '7987'
quality_controlled: '1'
related_material:
  record:
  - id: '5585'
    relation: popular_science
    status: public
  - id: '6371'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Evolutionary potential of transcription factors for gene regulatory rewiring
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 2
year: '2018'
...
---
_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. <i>Journal of the Royal Society Interface</i>. 2017;14(126). doi:<a href="https://doi.org/10.1098/rsif.2016.0139">10.1098/rsif.2016.0139</a>
  apa: Fernandes Redondo, R. A., de Vladar, H., Włodarski, T., &#38; Bollback, J.
    P. (2017). Evolutionary interplay between structure, energy and epistasis in the
    coat protein of the ϕX174 phage family. <i>Journal of the Royal Society Interface</i>.
    Royal Society of London. <a href="https://doi.org/10.1098/rsif.2016.0139">https://doi.org/10.1098/rsif.2016.0139</a>
  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.” <i>Journal of the Royal Society Interface</i>.
    Royal Society of London, 2017. <a href="https://doi.org/10.1098/rsif.2016.0139">https://doi.org/10.1098/rsif.2016.0139</a>.
  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,” <i>Journal of the Royal Society Interface</i>, 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.” <i>Journal
    of the Royal Society Interface</i>, vol. 14, no. 126, 20160139, Royal Society
    of London, 2017, doi:<a href="https://doi.org/10.1098/rsif.2016.0139">10.1098/rsif.2016.0139</a>.
  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: 2025-07-10T11:49:59Z
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:
  - 1742-5689
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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. <i>eLife</i>. 2017;6. doi:<a
    href="https://doi.org/10.7554/eLife.25192">10.7554/eLife.25192</a>
  apa: Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., &#38; Guet, C. C.
    (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element.
    <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.25192">https://doi.org/10.7554/eLife.25192</a>
  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.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href="https://doi.org/10.7554/eLife.25192">https://doi.org/10.7554/eLife.25192</a>.
  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,” <i>eLife</i>,
    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.” <i>ELife</i>, vol. 6, e25192, eLife Sciences Publications,
    2017, doi:<a href="https://doi.org/10.7554/eLife.25192">10.7554/eLife.25192</a>.
  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: 2025-07-10T12:01:50Z
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
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  creator: system
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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:
  - 2050-084X
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 6
year: '2017'
...
---
_id: '570'
abstract:
- lang: eng
  text: 'Most phenotypes are determined by molecular systems composed of specifically
    interacting molecules. However, unlike for individual components, little is known
    about the distributions of mutational effects of molecular systems as a whole.
    We ask how the distribution of mutational effects of a transcriptional regulatory
    system differs from the distributions of its components, by first independently,
    and then simultaneously, mutating a transcription factor and the associated promoter
    it represses. We find that the system distribution exhibits increased phenotypic
    variation compared to individual component distributions - an effect arising from
    intermolecular epistasis between the transcription factor and its DNA-binding
    site. In large part, this epistasis can be qualitatively attributed to the structure
    of the transcriptional regulatory system and could therefore be a common feature
    in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the
    constraints of individual components, thereby increasing phenotypic variation
    that selection could act on and facilitating adaptive evolution. '
article_number: e28921
article_processing_charge: No
author:
- first_name: Mato
  full_name: Lagator, Mato
  id: 345D25EC-F248-11E8-B48F-1D18A9856A87
  last_name: Lagator
- first_name: Srdjan
  full_name: Sarikas, Srdjan
  id: 35F0286E-F248-11E8-B48F-1D18A9856A87
  last_name: Sarikas
- first_name: Hande
  full_name: Acar, Hande
  id: 2DDF136A-F248-11E8-B48F-1D18A9856A87
  last_name: Acar
  orcid: 0000-0003-1986-9753
- 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, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure
    determines patterns of intermolecular epistasis. <i>eLife</i>. 2017;6. doi:<a
    href="https://doi.org/10.7554/eLife.28921">10.7554/eLife.28921</a>
  apa: Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., &#38; Guet, C. C. (2017).
    Regulatory network structure determines patterns of intermolecular epistasis.
    <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.28921">https://doi.org/10.7554/eLife.28921</a>
  chicago: Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin
    C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.”
    <i>ELife</i>. eLife Sciences Publications, 2017. <a href="https://doi.org/10.7554/eLife.28921">https://doi.org/10.7554/eLife.28921</a>.
  ieee: M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory
    network structure determines patterns of intermolecular epistasis,” <i>eLife</i>,
    vol. 6. eLife Sciences Publications, 2017.
  ista: Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network
    structure determines patterns of intermolecular epistasis. eLife. 6, e28921.
  mla: Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of
    Intermolecular Epistasis.” <i>ELife</i>, vol. 6, e28921, eLife Sciences Publications,
    2017, doi:<a href="https://doi.org/10.7554/eLife.28921">10.7554/eLife.28921</a>.
  short: M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017).
corr_author: '1'
date_created: 2018-12-11T11:47:14Z
date_published: 2017-11-13T00:00:00Z
date_updated: 2025-09-11T07:40:30Z
day: '13'
ddc:
- '576'
department:
- _id: CaGu
- _id: JoBo
- _id: NiBa
doi: 10.7554/eLife.28921
ec_funded: 1
external_id:
  isi:
  - '000425868200001'
file:
- access_level: open_access
  checksum: 273ab17f33305e4eaafd911ff88e7c5b
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:14:42Z
  date_updated: 2020-07-14T12:47:10Z
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  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:14:43Z
  date_updated: 2020-07-14T12:47:10Z
  file_id: '5097'
  file_name: IST-2017-918-v1+2_elife-28921-v3.pdf
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file_date_updated: 2020-07-14T12:47:10Z
has_accepted_license: '1'
intvolume: '         6'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _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:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
publist_id: '7244'
pubrep_id: '918'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Regulatory network structure determines patterns of intermolecular epistasis
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 6
year: '2017'
...
---
OA_place: publisher
_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:<a href="https://doi.org/10.15479/AT:ISTA:th_857">10.15479/AT:ISTA:th_857</a>
  apa: Jesse, F. (2017). <i>The lac operon in the wild</i>. Institute of Science and
    Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:th_857">https://doi.org/10.15479/AT:ISTA:th_857</a>
  chicago: Jesse, Fabienne. “The Lac Operon in the Wild.” Institute of Science and
    Technology Austria, 2017. <a href="https://doi.org/10.15479/AT:ISTA:th_857">https://doi.org/10.15479/AT:ISTA:th_857</a>.
  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. <i>The Lac Operon in the Wild</i>. Institute of Science and
    Technology Austria, 2017, doi:<a href="https://doi.org/10.15479/AT:ISTA:th_857">10.15479/AT:ISTA:th_857</a>.
  short: F. Jesse, The Lac Operon in the Wild, Institute of Science and Technology
    Austria, 2017.
corr_author: '1'
date_created: 2018-12-11T11:48:41Z
date_published: 2017-08-25T00:00:00Z
date_updated: 2026-04-08T14:18:16Z
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2017'
...
---
OA_place: publisher
_id: '6291'
abstract:
- lang: eng
  text: Bacteria and their pathogens – phages – are the most abundant living entities
    on Earth. Throughout their coevolution, bacteria have evolved multiple immune
    systems to overcome the ubiquitous threat from the phages. Although the molecu-
    lar details of these immune systems’ functions are relatively well understood,
    their epidemiological consequences for the phage-bacterial communities have been
    largely neglected. In this thesis we employed both experimental and theoretical
    methods to explore whether herd and social immunity may arise in bacterial popu-
    lations. Using our experimental system consisting of Escherichia coli strains
    with a CRISPR based immunity to the T7 phage we show that herd immunity arises
    in phage-bacterial communities and that it is accentuated when the populations
    are spatially structured. By fitting a mathematical model, we inferred expressions
    for the herd immunity threshold and the velocity of spread of a phage epidemic
    in partially resistant bacterial populations, which both depend on the bacterial
    growth rate, phage burst size and phage latent period. We also investigated the
    poten- tial for social immunity in Streptococcus thermophilus and its phage 2972
    using a bioinformatic analysis of potentially coding short open reading frames
    with a signalling signature, encoded within the CRISPR associated genes. Subsequently,
    we tested one identified potentially signalling peptide and found that its addition
    to a phage-challenged culture increases probability of survival of bacteria two
    fold, although the results were only marginally significant. Together, these results
    demonstrate that the ubiquitous arms races between bacteria and phages have further
    consequences at the level of the population.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Pavel
  full_name: Payne, Pavel
  id: 35F78294-F248-11E8-B48F-1D18A9856A87
  last_name: Payne
  orcid: 0000-0002-2711-9453
citation:
  ama: Payne P. Bacterial herd and social immunity to phages. 2017.
  apa: Payne, P. (2017). <i>Bacterial herd and social immunity to phages</i>. Institute
    of Science and Technology Austria.
  chicago: Payne, Pavel. “Bacterial Herd and Social Immunity to Phages.” Institute
    of Science and Technology Austria, 2017.
  ieee: P. Payne, “Bacterial herd and social immunity to phages,” Institute of Science
    and Technology Austria, 2017.
  ista: Payne P. 2017. Bacterial herd and social immunity to phages. Institute of
    Science and Technology Austria.
  mla: Payne, Pavel. <i>Bacterial Herd and Social Immunity to Phages</i>. Institute
    of Science and Technology Austria, 2017.
  short: P. Payne, Bacterial Herd and Social Immunity to Phages, Institute of Science
    and Technology Austria, 2017.
corr_author: '1'
date_created: 2019-04-09T15:16:45Z
date_published: 2017-02-01T00:00:00Z
date_updated: 2026-04-08T14:16:28Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: NiBa
- _id: JoBo
file:
- access_level: closed
  checksum: a0fc5c26a89c0ea759947ffba87d0d8f
  content_type: application/pdf
  creator: dernst
  date_created: 2019-04-09T15:15:32Z
  date_updated: 2020-07-14T12:47:27Z
  file_id: '6292'
  file_name: thesis_pavel_payne_final_w_signature_page.pdf
  file_size: 3025175
  relation: main_file
- access_level: open_access
  checksum: af531e921a7f64a9e0af4cd8783b2226
  content_type: application/pdf
  creator: dernst
  date_created: 2021-02-22T13:45:59Z
  date_updated: 2021-02-22T13:45:59Z
  file_id: '9187'
  file_name: 2017_Payne_Thesis.pdf
  file_size: 3111536
  relation: main_file
  success: 1
file_date_updated: 2021-02-22T13:45:59Z
has_accepted_license: '1'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: '83'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
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
- first_name: Nicholas H
  full_name: Barton, Nicholas H
  id: 4880FE40-F248-11E8-B48F-1D18A9856A87
  last_name: Barton
  orcid: 0000-0002-8548-5240
title: Bacterial herd and social immunity to phages
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
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.
article_processing_charge: No
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. <i>Molecular Biology and Evolution</i>.
    2016;33(3):761-769. doi:<a href="https://doi.org/10.1093/molbev/msv269">10.1093/molbev/msv269</a>
  apa: Lagator, M., Igler, C., Moreno, A., Guet, C. C., &#38; Bollback, J. P. (2016).
    Epistatic interactions in the arabinose cis-regulatory element. <i>Molecular Biology
    and Evolution</i>. Oxford University Press. <a href="https://doi.org/10.1093/molbev/msv269">https://doi.org/10.1093/molbev/msv269</a>
  chicago: Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan
    P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.”
    <i>Molecular Biology and Evolution</i>. Oxford University Press, 2016. <a href="https://doi.org/10.1093/molbev/msv269">https://doi.org/10.1093/molbev/msv269</a>.
  ieee: M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic
    interactions in the arabinose cis-regulatory element,” <i>Molecular Biology and
    Evolution</i>, 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.” <i>Molecular Biology and Evolution</i>, vol. 33, no. 3, Oxford University
    Press, 2016, pp. 761–69, doi:<a href="https://doi.org/10.1093/molbev/msv269">10.1093/molbev/msv269</a>.
  short: M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology
    and Evolution 33 (2016) 761–769.
corr_author: '1'
date_created: 2018-12-11T11:51:57Z
date_published: 2016-03-01T00:00:00Z
date_updated: 2025-09-18T14:11:47Z
day: '01'
ddc:
- '570'
- '576'
department:
- _id: CaGu
- _id: JoBo
doi: 10.1093/molbev/msv269
ec_funded: 1
external_id:
  isi:
  - '000371219500014'
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'
isi: 1
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 33
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:<a href="https://doi.org/10.6084/m9.figshare.4315652.v1">10.6084/m9.figshare.4315652.v1</a>
  apa: Fernandes Redondo, R. A., de Vladar, H., Włodarski, T., &#38; 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. <a href="https://doi.org/10.6084/m9.figshare.4315652.v1">https://doi.org/10.6084/m9.figshare.4315652.v1</a>
  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. <a href="https://doi.org/10.6084/m9.figshare.4315652.v1">https://doi.org/10.6084/m9.figshare.4315652.v1</a>.
  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, <a href="https://doi.org/10.6084/m9.figshare.4315652.v1">10.6084/m9.figshare.4315652.v1</a>.
  mla: Fernandes Redondo, Rodrigo A., et al. <i>Data from Evolutionary Interplay between
    Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family</i>.
    The Royal Society, 2016, doi:<a href="https://doi.org/10.6084/m9.figshare.4315652.v1">10.6084/m9.figshare.4315652.v1</a>.
  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: 2025-07-10T11:49:59Z
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'
...
---
OA_place: publisher
_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). <i>Selective barriers to horizontal gene transfer</i>. 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. <i>Selective Barriers to Horizontal Gene Transfer</i>. Institute
    of Science and Technology Austria, 2016.
  short: H. Acar, Selective Barriers to Horizontal Gene Transfer, Institute of Science
    and Technology Austria, 2016.
corr_author: '1'
date_created: 2018-12-11T11:50:16Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2026-04-09T10:51:38Z
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
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:<a href="https://doi.org/10.15479/AT:ISTA:43">10.15479/AT:ISTA:43</a>
  apa: Tugrul, M. (2016). Experimental Data for Binding Site Evolution of Bacterial
    RNA Polymerase. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:43">https://doi.org/10.15479/AT:ISTA:43</a>
  chicago: Tugrul, Murat. “Experimental Data for Binding Site Evolution of Bacterial
    RNA Polymerase.” Institute of Science and Technology Austria, 2016. <a href="https://doi.org/10.15479/AT:ISTA:43">https://doi.org/10.15479/AT:ISTA:43</a>.
  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, <a href="https://doi.org/10.15479/AT:ISTA:43">10.15479/AT:ISTA:43</a>.
  mla: Tugrul, Murat. <i>Experimental Data for Binding Site Evolution of Bacterial
    RNA Polymerase</i>. Institute of Science and Technology Austria, 2016, doi:<a
    href="https://doi.org/10.15479/AT:ISTA:43">10.15479/AT:ISTA:43</a>.
  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: 2026-04-09T10:52:40Z
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: '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'
article_processing_charge: No
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. <i>BMC Genomics</i>. 2014;15(1). doi:<a href="https://doi.org/10.1186/1471-2164-15-663">10.1186/1471-2164-15-663</a>
  apa: Kupczok, A., &#38; Bollback, J. P. (2014). Motif depletion in bacteriophages
    infecting hosts with CRISPR systems. <i>BMC Genomics</i>. BioMed Central. <a href="https://doi.org/10.1186/1471-2164-15-663">https://doi.org/10.1186/1471-2164-15-663</a>
  chicago: Kupczok, Anne, and Jonathan P Bollback. “Motif Depletion in Bacteriophages
    Infecting Hosts with CRISPR Systems.” <i>BMC Genomics</i>. BioMed Central, 2014.
    <a href="https://doi.org/10.1186/1471-2164-15-663">https://doi.org/10.1186/1471-2164-15-663</a>.
  ieee: A. Kupczok and J. P. Bollback, “Motif depletion in bacteriophages infecting
    hosts with CRISPR systems,” <i>BMC Genomics</i>, 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.” <i>BMC Genomics</i>, vol. 15, no. 1, 663,
    BioMed Central, 2014, doi:<a href="https://doi.org/10.1186/1471-2164-15-663">10.1186/1471-2164-15-663</a>.
  short: A. Kupczok, J.P. Bollback, BMC Genomics 15 (2014).
corr_author: '1'
date_created: 2018-12-11T11:55:23Z
date_published: 2014-08-08T00:00:00Z
date_updated: 2025-09-29T11:52:17Z
day: '08'
ddc:
- '570'
department:
- _id: JoBo
doi: 10.1186/1471-2164-15-663
external_id:
  isi:
  - '000341528300001'
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'
isi: 1
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 15
year: '2014'
...
---
OA_place: publisher
OA_type: free access
_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. <i>Molecular
    Biology and Evolution</i>. 2014;31(1):232-238. doi:<a href="https://doi.org/10.1093/molbev/mst187">10.1093/molbev/mst187</a>
  apa: Hall, B., Acar, H., Nandipati, A., &#38; Barlow, M. (2014). Growth rates made
    easy. <i>Molecular Biology and Evolution</i>. Oxford University Press. <a href="https://doi.org/10.1093/molbev/mst187">https://doi.org/10.1093/molbev/mst187</a>
  chicago: Hall, Barry, Hande Acar, Anna Nandipati, and Miriam Barlow. “Growth Rates
    Made Easy.” <i>Molecular Biology and Evolution</i>. Oxford University Press, 2014.
    <a href="https://doi.org/10.1093/molbev/mst187">https://doi.org/10.1093/molbev/mst187</a>.
  ieee: B. Hall, H. Acar, A. Nandipati, and M. Barlow, “Growth rates made easy,” <i>Molecular
    Biology and Evolution</i>, 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.” <i>Molecular Biology and Evolution</i>,
    vol. 31, no. 1, Oxford University Press, 2014, pp. 232–38, doi:<a href="https://doi.org/10.1093/molbev/mst187">10.1093/molbev/mst187</a>.
  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: 2025-09-29T12:29:33Z
day: '01'
department:
- _id: JoBo
doi: 10.1093/molbev/mst187
external_id:
  isi:
  - '000329253200022'
  pmid:
  - '24170494'
intvolume: '        31'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1093/molbev/mst187
month: '01'
oa: 1
oa_version: Published Version
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 31
year: '2014'
...
---
_id: '2410'
abstract:
- lang: eng
  text: 'Here, we describe a novel virulent bacteriophage that infects Bacillus weihenstephanensis,
    isolated from soil in Austria. It is the first phage to be discovered that infects
    this species. Here, we present the complete genome sequence of this podovirus. '
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: Anne
  full_name: Kupczok, Anne
  id: 2BB22BC2-F248-11E8-B48F-1D18A9856A87
  last_name: Kupczok
- first_name: Gertraud
  full_name: Stift, Gertraud
  id: 2DB195CA-F248-11E8-B48F-1D18A9856A87
  last_name: Stift
- 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, Kupczok A, Stift G, Bollback JP. Complete genome sequence
    of the novel phage MG-B1 infecting bacillus weihenstephanensis. <i>Genome Announcements</i>.
    2013;1(3). doi:<a href="https://doi.org/10.1128/genomeA.00216-13">10.1128/genomeA.00216-13</a>
  apa: Fernandes Redondo, R. A., Kupczok, A., Stift, G., &#38; Bollback, J. P. (2013).
    Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis.
    <i>Genome Announcements</i>. American Society for Microbiology. <a href="https://doi.org/10.1128/genomeA.00216-13">https://doi.org/10.1128/genomeA.00216-13</a>
  chicago: Fernandes Redondo, Rodrigo A, Anne Kupczok, Gertraud Stift, and Jonathan
    P Bollback. “Complete Genome Sequence of the Novel Phage MG-B1 Infecting Bacillus
    Weihenstephanensis.” <i>Genome Announcements</i>. American Society for Microbiology,
    2013. <a href="https://doi.org/10.1128/genomeA.00216-13">https://doi.org/10.1128/genomeA.00216-13</a>.
  ieee: R. A. Fernandes Redondo, A. Kupczok, G. Stift, and J. P. Bollback, “Complete
    genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis,”
    <i>Genome Announcements</i>, vol. 1, no. 3. American Society for Microbiology,
    2013.
  ista: Fernandes Redondo RA, Kupczok A, Stift G, Bollback JP. 2013. Complete genome
    sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis. Genome
    Announcements. 1(3).
  mla: Fernandes Redondo, Rodrigo A., et al. “Complete Genome Sequence of the Novel
    Phage MG-B1 Infecting Bacillus Weihenstephanensis.” <i>Genome Announcements</i>,
    vol. 1, no. 3, American Society for Microbiology, 2013, doi:<a href="https://doi.org/10.1128/genomeA.00216-13">10.1128/genomeA.00216-13</a>.
  short: R.A. Fernandes Redondo, A. Kupczok, G. Stift, J.P. Bollback, Genome Announcements
    1 (2013).
corr_author: '1'
date_created: 2018-12-11T11:57:30Z
date_published: 2013-06-13T00:00:00Z
date_updated: 2024-10-09T20:55:15Z
day: '13'
ddc:
- '576'
department:
- _id: JoBo
- _id: LifeSc
doi: 10.1128/genomeA.00216-13
file:
- access_level: open_access
  checksum: 0751ec74b695567e0cdf02aaf9c26829
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:17:36Z
  date_updated: 2020-07-14T12:45:40Z
  file_id: '5291'
  file_name: IST-2015-398-v1+1_Genome_Announc.-2013-Redondo-.pdf
  file_size: 130026
  relation: main_file
file_date_updated: 2020-07-14T12:45:40Z
has_accepted_license: '1'
intvolume: '         1'
issue: '3'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
publication: Genome Announcements
publication_status: published
publisher: American Society for Microbiology
publist_id: '4516'
pubrep_id: '398'
quality_controlled: '1'
scopus_import: 1
status: public
title: Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2013'
...
---
_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.'
article_processing_charge: No
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
    . <i>BMC Evolutionary Biology</i>. 2013;13(1):54-54. doi:<a href="https://doi.org/10.1186/1471-2148-13-54">10.1186/1471-2148-13-54</a>
  apa: Kupczok, A., &#38; Bollback, J. P. (2013). Probabilistic models for CRISPR
    spacer content evolution . <i>BMC Evolutionary Biology</i>. BioMed Central. <a
    href="https://doi.org/10.1186/1471-2148-13-54">https://doi.org/10.1186/1471-2148-13-54</a>
  chicago: Kupczok, Anne, and Jonathan P Bollback. “Probabilistic Models for CRISPR
    Spacer Content Evolution .” <i>BMC Evolutionary Biology</i>. BioMed Central, 2013.
    <a href="https://doi.org/10.1186/1471-2148-13-54">https://doi.org/10.1186/1471-2148-13-54</a>.
  ieee: A. Kupczok and J. P. Bollback, “Probabilistic models for CRISPR spacer content
    evolution ,” <i>BMC Evolutionary Biology</i>, 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 .” <i>BMC Evolutionary Biology</i>, vol. 13, no. 1, BioMed Central,
    2013, pp. 54–54, doi:<a href="https://doi.org/10.1186/1471-2148-13-54">10.1186/1471-2148-13-54</a>.
  short: A. Kupczok, J.P. Bollback, BMC Evolutionary Biology 13 (2013) 54–54.
corr_author: '1'
date_created: 2018-12-11T11:57:31Z
date_published: 2013-02-26T00:00:00Z
date_updated: 2025-09-29T14:15:59Z
day: '26'
ddc:
- '576'
department:
- _id: JoBo
doi: 10.1186/1471-2148-13-54
external_id:
  isi:
  - '000321524500001'
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'
isi: 1
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 13
year: '2013'
...
---
_id: '500'
abstract:
- lang: eng
  text: 'Background: Reassortment between the RNA segments encoding haemagglutinin
    (HA) and neuraminidase (NA), the major antigenic influenza proteins, produces
    viruses with novel HA and NA subtype combinations and has preceded the emergence
    of pandemic strains. It has been suggested that productive viral infection requires
    a balance in the level of functional activity of HA and NA, arising from their
    closely interacting roles in the viral life cycle, and that this functional balance
    could be mediated by genetic changes in the HA and NA. Here, we investigate how
    the selective pressure varies for H7 avian influenza HA on different NA subtype
    backgrounds. Results: By extending Bayesian stochastic mutational mapping methods
    to calculate the ratio of the rate of non-synonymous change to the rate of synonymous
    change (d N/d S), we found the average d N/d S across the avian influenza H7 HA1
    region to be significantly greater on an N2 NA subtype background than on an N1,
    N3 or N7 background. Observed differences in evolutionary rates of H7 HA on different
    NA subtype backgrounds could not be attributed to underlying differences between
    avian host species or virus pathogenicity. Examination of d N/d S values for each
    subtype on a site-by-site basis indicated that the elevated d N/d S on the N2
    NA background was a result of increased selection, rather than a relaxation of
    selective constraint. Conclusions: Our results are consistent with the hypothesis
    that reassortment exposes influenza HA to significant changes in selective pressure
    through genetic interactions with NA. Such epistatic effects might be explicitly
    accounted for in future models of influenza evolution.'
acknowledgement: "This work was supported by the Biotechnology and Biological Sciences
  Research Council, the Government of the Republic of Panama, the Interdisciplinary
  Centre for Human and Avian Influenza Research (www.ichair-flu.org) funded by the
  Scottish Funding Council, and the Institute for Science and Technology Austria.\r\nCC
  BY 2.0\r\n"
article_number: '222'
article_processing_charge: No
author:
- first_name: Melissa
  full_name: Ward, Melissa
  last_name: Ward
- first_name: Samantha
  full_name: Lycett, Samantha
  last_name: Lycett
- first_name: Dorita
  full_name: Avila, Dorita
  last_name: Avila
- 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: Andrew
  full_name: Leigh Brown, Andrew
  last_name: Leigh Brown
citation:
  ama: Ward M, Lycett S, Avila D, Bollback JP, Leigh Brown A. Evolutionary interactions
    between haemagglutinin and neuraminidase in avian influenza. <i>BMC Evolutionary
    Biology</i>. 2013;13(1). doi:<a href="https://doi.org/10.1186/1471-2148-13-222">10.1186/1471-2148-13-222</a>
  apa: Ward, M., Lycett, S., Avila, D., Bollback, J. P., &#38; Leigh Brown, A. (2013).
    Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza.
    <i>BMC Evolutionary Biology</i>. BioMed Central. <a href="https://doi.org/10.1186/1471-2148-13-222">https://doi.org/10.1186/1471-2148-13-222</a>
  chicago: Ward, Melissa, Samantha Lycett, Dorita Avila, Jonathan P Bollback, and
    Andrew Leigh Brown. “Evolutionary Interactions between Haemagglutinin and Neuraminidase
    in Avian Influenza.” <i>BMC Evolutionary Biology</i>. BioMed Central, 2013. <a
    href="https://doi.org/10.1186/1471-2148-13-222">https://doi.org/10.1186/1471-2148-13-222</a>.
  ieee: M. Ward, S. Lycett, D. Avila, J. P. Bollback, and A. Leigh Brown, “Evolutionary
    interactions between haemagglutinin and neuraminidase in avian influenza,” <i>BMC
    Evolutionary Biology</i>, vol. 13, no. 1. BioMed Central, 2013.
  ista: Ward M, Lycett S, Avila D, Bollback JP, Leigh Brown A. 2013. Evolutionary
    interactions between haemagglutinin and neuraminidase in avian influenza. BMC
    Evolutionary Biology. 13(1), 222.
  mla: Ward, Melissa, et al. “Evolutionary Interactions between Haemagglutinin and
    Neuraminidase in Avian Influenza.” <i>BMC Evolutionary Biology</i>, vol. 13, no.
    1, 222, BioMed Central, 2013, doi:<a href="https://doi.org/10.1186/1471-2148-13-222">10.1186/1471-2148-13-222</a>.
  short: M. Ward, S. Lycett, D. Avila, J.P. Bollback, A. Leigh Brown, BMC Evolutionary
    Biology 13 (2013).
date_created: 2018-12-11T11:46:49Z
date_published: 2013-10-09T00:00:00Z
date_updated: 2025-09-30T07:28:51Z
day: '09'
ddc:
- '576'
department:
- _id: JoBo
doi: 10.1186/1471-2148-13-222
external_id:
  isi:
  - '000326620200001'
file:
- access_level: open_access
  checksum: 52cf48a7c1794676ae8b0029573a84a9
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:08:59Z
  date_updated: 2020-07-14T12:46:36Z
  file_id: '4722'
  file_name: IST-2018-941-v1+1_2013_Bollback_Evolutionary_interactionspdf.pdf
  file_size: 1150052
  relation: main_file
file_date_updated: 2020-07-14T12:46:36Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
issue: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
publication: BMC Evolutionary Biology
publication_status: published
publisher: BioMed Central
publist_id: '7320'
pubrep_id: '941'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Evolutionary interactions between haemagglutinin and neuraminidase in avian
  influenza
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 13
year: '2013'
...
---
_id: '501'
abstract:
- lang: eng
  text: 'All known species of extant tapirs are allopatric: 1 in southeastern Asia
    and 3 in Central and South America. The fossil record for tapirs, however, is
    much wider in geographical range, including Europe, Asia, and North and South
    America, going back to the late Oligocene, making the present distribution a relict
    of the original one. We here describe a new species of living Tapirus from the
    Amazon rain forest, the 1st since T. bairdii Gill, 1865, and the 1st new Perissodactyla
    in more than 100 years, from both morphological and molecular characters. It is
    shorter in stature than T. terrestris (Linnaeus, 1758) and has distinctive skull
    morphology, and it is basal to the clade formed by T. terrestris and T. pinchaque
    (Roulin, 1829). This highlights the unrecognized biodiversity in western Amazonia,
    where the biota faces increasing threats. Local peoples have long recognized our
    new species, suggesting a key role for traditional knowledge in understanding
    the biodiversity of the region.'
article_processing_charge: No
author:
- first_name: Mario
  full_name: Cozzuol, Mario
  last_name: Cozzuol
- first_name: Camila
  full_name: Clozato, Camila
  last_name: Clozato
- first_name: Elizete
  full_name: Holanda, Elizete
  last_name: Holanda
- first_name: Flávio
  full_name: Rodrigues, Flávio
  last_name: Rodrigues
- first_name: Samuel
  full_name: Nienow, Samuel
  last_name: Nienow
- first_name: Benoit
  full_name: De Thoisy, Benoit
  last_name: De Thoisy
- 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: Fabrício
  full_name: Santos, Fabrício
  last_name: Santos
citation:
  ama: Cozzuol M, Clozato C, Holanda E, et al. A new species of tapir from the Amazon.
    <i>Journal of Mammalogy</i>. 2013;94(6):1331-1345. doi:<a href="https://doi.org/10.1644/12-MAMM-A-169.1">10.1644/12-MAMM-A-169.1</a>
  apa: Cozzuol, M., Clozato, C., Holanda, E., Rodrigues, F., Nienow, S., De Thoisy,
    B., … Santos, F. (2013). A new species of tapir from the Amazon. <i>Journal of
    Mammalogy</i>. Oxford University Press. <a href="https://doi.org/10.1644/12-MAMM-A-169.1">https://doi.org/10.1644/12-MAMM-A-169.1</a>
  chicago: Cozzuol, Mario, Camila Clozato, Elizete Holanda, Flávio Rodrigues, Samuel
    Nienow, Benoit De Thoisy, Rodrigo A Fernandes Redondo, and Fabrício Santos. “A
    New Species of Tapir from the Amazon.” <i>Journal of Mammalogy</i>. Oxford University
    Press, 2013. <a href="https://doi.org/10.1644/12-MAMM-A-169.1">https://doi.org/10.1644/12-MAMM-A-169.1</a>.
  ieee: M. Cozzuol <i>et al.</i>, “A new species of tapir from the Amazon,” <i>Journal
    of Mammalogy</i>, vol. 94, no. 6. Oxford University Press, pp. 1331–1345, 2013.
  ista: Cozzuol M, Clozato C, Holanda E, Rodrigues F, Nienow S, De Thoisy B, Fernandes
    Redondo RA, Santos F. 2013. A new species of tapir from the Amazon. Journal of
    Mammalogy. 94(6), 1331–1345.
  mla: Cozzuol, Mario, et al. “A New Species of Tapir from the Amazon.” <i>Journal
    of Mammalogy</i>, vol. 94, no. 6, Oxford University Press, 2013, pp. 1331–45,
    doi:<a href="https://doi.org/10.1644/12-MAMM-A-169.1">10.1644/12-MAMM-A-169.1</a>.
  short: M. Cozzuol, C. Clozato, E. Holanda, F. Rodrigues, S. Nienow, B. De Thoisy,
    R.A. Fernandes Redondo, F. Santos, Journal of Mammalogy 94 (2013) 1331–1345.
date_created: 2018-12-11T11:46:49Z
date_published: 2013-12-01T00:00:00Z
date_updated: 2025-09-30T07:28:20Z
day: '01'
ddc:
- '570'
department:
- _id: JoBo
doi: 10.1644/12-MAMM-A-169.1
external_id:
  isi:
  - '000329010200015'
file:
- access_level: open_access
  checksum: 8007815078dccac21ecd1cf73a269dc6
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:12:59Z
  date_updated: 2020-07-14T12:46:36Z
  file_id: '4980'
  file_name: IST-2018-940-v1+1_2013_Redondo_A_new.pdf
  file_size: 1040765
  relation: main_file
file_date_updated: 2020-07-14T12:46:36Z
has_accepted_license: '1'
intvolume: '        94'
isi: 1
issue: '6'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 1331 - 1345
publication: Journal of Mammalogy
publication_status: published
publisher: Oxford University Press
publist_id: '7319'
pubrep_id: '940'
quality_controlled: '1'
scopus_import: '1'
status: public
title: A new species of tapir from the Amazon
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 94
year: '2013'
...
---
_id: '508'
abstract:
- lang: eng
  text: The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen
    species with microbicidal activity. It is composed of two membrane-spanning subunits,
    gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic
    subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively).
    Mutations in any of these genes can result in chronic granulomatous disease, a
    primary immunodeficiency characterized by recurrent infections. Using evolutionary
    mapping, we determined that episodes of adaptive natural selection have shaped
    the extracellular portion of gp91-phox during the evolution of mammals, which
    suggests that this region may have a function in host-pathogen interactions. On
    the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2,
    and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of
    European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the
    pattern of CYBA diversity is compatible with balancing natural selection, perhaps
    mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern
    of diversity characterized by a differentiated haplotype structure. Our study
    provides insight into the role of pathogen-driven natural selection in an innate
    immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic
    NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other
    complex diseases.
article_processing_charge: No
author:
- first_name: Eduardo
  full_name: Tarazona Santos, Eduardo
  last_name: Tarazona Santos
- first_name: Moara
  full_name: Machado, Moara
  last_name: Machado
- first_name: Wagner
  full_name: Magalhães, Wagner
  last_name: Magalhães
- first_name: Renee
  full_name: Chen, Renee
  last_name: Chen
- first_name: Fernanda
  full_name: Lyon, Fernanda
  last_name: Lyon
- first_name: Laurie
  full_name: Burdett, Laurie
  last_name: Burdett
- first_name: Andrew
  full_name: Crenshaw, Andrew
  last_name: Crenshaw
- first_name: Cristina
  full_name: Fabbri, Cristina
  last_name: Fabbri
- first_name: Latife
  full_name: Pereira, Latife
  last_name: Pereira
- first_name: Laelia
  full_name: Pinto, Laelia
  last_name: Pinto
- 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: Ben
  full_name: Sestanovich, Ben
  last_name: Sestanovich
- first_name: Meredith
  full_name: Yeager, Meredith
  last_name: Yeager
- first_name: Stephen
  full_name: Chanock, Stephen
  last_name: Chanock
citation:
  ama: 'Tarazona Santos E, Machado M, Magalhães W, et al. Evolutionary dynamics of
    the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications.
    <i>Molecular Biology and Evolution</i>. 2013;30(9):2157-2167. doi:<a href="https://doi.org/10.1093/molbev/mst119">10.1093/molbev/mst119</a>'
  apa: 'Tarazona Santos, E., Machado, M., Magalhães, W., Chen, R., Lyon, F., Burdett,
    L., … Chanock, S. (2013). Evolutionary dynamics of the human NADPH oxidase genes
    CYBB, CYBA, NCF2, and NCF4: Functional implications. <i>Molecular Biology and
    Evolution</i>. Oxford University Press. <a href="https://doi.org/10.1093/molbev/mst119">https://doi.org/10.1093/molbev/mst119</a>'
  chicago: 'Tarazona Santos, Eduardo, Moara Machado, Wagner Magalhães, Renee Chen,
    Fernanda Lyon, Laurie Burdett, Andrew Crenshaw, et al. “Evolutionary Dynamics
    of the Human NADPH Oxidase Genes CYBB, CYBA, NCF2, and NCF4: Functional Implications.”
    <i>Molecular Biology and Evolution</i>. Oxford University Press, 2013. <a href="https://doi.org/10.1093/molbev/mst119">https://doi.org/10.1093/molbev/mst119</a>.'
  ieee: 'E. Tarazona Santos <i>et al.</i>, “Evolutionary dynamics of the human NADPH
    oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications,” <i>Molecular
    Biology and Evolution</i>, vol. 30, no. 9. Oxford University Press, pp. 2157–2167,
    2013.'
  ista: 'Tarazona Santos E, Machado M, Magalhães W, Chen R, Lyon F, Burdett L, Crenshaw
    A, Fabbri C, Pereira L, Pinto L, Fernandes Redondo RA, Sestanovich B, Yeager M,
    Chanock S. 2013. Evolutionary dynamics of the human NADPH oxidase genes CYBB,
    CYBA, NCF2, and NCF4: Functional implications. Molecular Biology and Evolution.
    30(9), 2157–2167.'
  mla: 'Tarazona Santos, Eduardo, et al. “Evolutionary Dynamics of the Human NADPH
    Oxidase Genes CYBB, CYBA, NCF2, and NCF4: Functional Implications.” <i>Molecular
    Biology and Evolution</i>, vol. 30, no. 9, Oxford University Press, 2013, pp.
    2157–67, doi:<a href="https://doi.org/10.1093/molbev/mst119">10.1093/molbev/mst119</a>.'
  short: E. Tarazona Santos, M. Machado, W. Magalhães, R. Chen, F. Lyon, L. Burdett,
    A. Crenshaw, C. Fabbri, L. Pereira, L. Pinto, R.A. Fernandes Redondo, B. Sestanovich,
    M. Yeager, S. Chanock, Molecular Biology and Evolution 30 (2013) 2157–2167.
date_created: 2018-12-11T11:46:52Z
date_published: 2013-09-01T00:00:00Z
date_updated: 2025-09-30T07:13:08Z
day: '01'
department:
- _id: JoBo
doi: 10.1093/molbev/mst119
external_id:
  isi:
  - '000323616600014'
  pmid:
  - '23821607'
intvolume: '        30'
isi: 1
issue: '9'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748357/
month: '09'
oa: 1
oa_version: Submitted Version
page: 2157 - 2167
pmid: 1
publication: Molecular Biology and Evolution
publication_status: published
publisher: Oxford University Press
publist_id: '7310'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and
  NCF4: Functional implications'
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 30
year: '2013'
...
---
_id: '2963'
abstract:
- lang: eng
  text: 'Zebra finches are an ubiquitous model system for the study of vocal learning
    in animal communication. Their song has been well described, but its possible
    function(s) in social communication are only partly understood. The so-called
    ‘directed song’ is a high-intensity, high-performance song given during courtship
    in close proximity to the female, which is known to mediate mate choice and mating.
    However, this singing mode constitutes only a fraction of zebra finch males’ prolific
    song output. Potential communicative functions of their second, ‘undirected’ singing
    mode remain unresolved in the face of contradicting reports of both facilitating
    and inhibiting effects of social company on singing. We addressed this issue by
    experimentally manipulating social contexts in a within-subject design, comparing
    a solo versus male or female only company condition, each lasting for 24 hours.
    Males’ total song output was significantly higher when a conspecific was in audible
    and visible distance than when they were alone. Male and female company had an
    equally facilitating effect on song output. Our findings thus indicate that singing
    motivation is facilitated rather than inhibited by social company, suggesting
    that singing in zebra finches might function both in inter- and intrasexual communication. '
article_processing_charge: No
author:
- first_name: Fabienne
  full_name: Jesse, Fabienne
  id: 4C8C26A4-F248-11E8-B48F-1D18A9856A87
  last_name: Jesse
- first_name: Katharina
  full_name: Riebel, Katharina
  last_name: Riebel
citation:
  ama: Jesse F, Riebel K. Social facilitation of male song by male and female conspecifics
    in the zebra finch, Taeniopygia guttata. <i>Behavioural Processes</i>. 2012;91(3):262-266.
    doi:<a href="https://doi.org/10.1016/j.beproc.2012.09.006">10.1016/j.beproc.2012.09.006</a>
  apa: Jesse, F., &#38; Riebel, K. (2012). Social facilitation of male song by male
    and female conspecifics in the zebra finch, Taeniopygia guttata. <i>Behavioural
    Processes</i>. Elsevier. <a href="https://doi.org/10.1016/j.beproc.2012.09.006">https://doi.org/10.1016/j.beproc.2012.09.006</a>
  chicago: Jesse, Fabienne, and Katharina Riebel. “Social Facilitation of Male Song
    by Male and Female Conspecifics in the Zebra Finch, Taeniopygia Guttata.” <i>Behavioural
    Processes</i>. Elsevier, 2012. <a href="https://doi.org/10.1016/j.beproc.2012.09.006">https://doi.org/10.1016/j.beproc.2012.09.006</a>.
  ieee: F. Jesse and K. Riebel, “Social facilitation of male song by male and female
    conspecifics in the zebra finch, Taeniopygia guttata,” <i>Behavioural Processes</i>,
    vol. 91, no. 3. Elsevier, pp. 262–266, 2012.
  ista: Jesse F, Riebel K. 2012. Social facilitation of male song by male and female
    conspecifics in the zebra finch, Taeniopygia guttata. Behavioural Processes. 91(3),
    262–266.
  mla: Jesse, Fabienne, and Katharina Riebel. “Social Facilitation of Male Song by
    Male and Female Conspecifics in the Zebra Finch, Taeniopygia Guttata.” <i>Behavioural
    Processes</i>, vol. 91, no. 3, Elsevier, 2012, pp. 262–66, doi:<a href="https://doi.org/10.1016/j.beproc.2012.09.006">10.1016/j.beproc.2012.09.006</a>.
  short: F. Jesse, K. Riebel, Behavioural Processes 91 (2012) 262–266.
corr_author: '1'
date_created: 2018-12-11T12:00:35Z
date_published: 2012-11-01T00:00:00Z
date_updated: 2025-09-30T08:05:37Z
day: '01'
department:
- _id: JoBo
doi: 10.1016/j.beproc.2012.09.006
external_id:
  isi:
  - '000311660200007'
intvolume: '        91'
isi: 1
issue: '3'
language:
- iso: eng
month: '11'
oa_version: None
page: 262 - 266
publication: Behavioural Processes
publication_status: published
publisher: Elsevier
publist_id: '3756'
quality_controlled: '1'
status: public
title: Social facilitation of male song by male and female conspecifics in the zebra
  finch, Taeniopygia guttata
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 91
year: '2012'
...
