---
OA_place: publisher
OA_type: hybrid
_id: '18936'
abstract:
- lang: eng
  text: A major obstacle to predictive understanding of evolution stems from the complexity
    of biological systems, which prevents detailed characterization of key evolutionary
    properties. Here, we highlight some of the major sources of complexity that arise
    when relating molecular mechanisms to their evolutionary consequences and ask
    whether accounting for every mechanistic detail is important to accurately predict
    evolutionary outcomes. To do this, we developed a mechanistic model of a bacterial
    promoter regulated by 2 proteins, allowing us to connect any promoter genotype
    to 6 phenotypes that capture the dynamics of gene expression following an environmental
    switch. Accounting for the mechanisms that govern how this system works enabled
    us to provide an in-depth picture of how regulated bacterial promoters might evolve.
    More importantly, we used the model to explore which factors that contribute to
    the complexity of this system are essential for understanding its evolution, and
    which can be simplified without information loss. We found that several key evolutionary
    properties—the distribution of phenotypic and fitness effects of mutations, the
    evolutionary trajectories during selection for regulation—can be accurately captured
    without accounting for all, or even most, parameters of the system. Our findings
    point to the need for a mechanistic approach to studying evolution, as it enables
    tackling biological complexity and in doing so improves the ability to predict
    evolutionary outcomes.
acknowledgement: "The authors thank Nick Barton, Stepan Denisov, Claudia Igler, Srdjan
  Sarikas, Anna Staron, and the anonymous reviewers for useful comments and discussions
  that helped improve our work.\r\nFunding for this work was provided by the Wellcome
  Trust–Royal Society Sir Henry Dale Fellowship (216779/Z/19/Z) and the Royal Society
  Research Grant (RG\\R2\\232522) to M.L."
article_number: iyae191
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Rok
  full_name: Grah, Rok
  id: 483E70DE-F248-11E8-B48F-1D18A9856A87
  last_name: Grah
  orcid: 0000-0003-2539-3560
- 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: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Mato
  full_name: Lagator, Mato
  id: 345D25EC-F248-11E8-B48F-1D18A9856A87
  last_name: Lagator
citation:
  ama: 'Grah R, Guet CC, Tkačik G, Lagator M. Linking molecular mechanisms to their
    evolutionary consequences: a primer. <i>Genetics</i>. 2025;229(2). doi:<a href="https://doi.org/10.1093/genetics/iyae191">10.1093/genetics/iyae191</a>'
  apa: 'Grah, R., Guet, C. C., Tkačik, G., &#38; Lagator, M. (2025). Linking molecular
    mechanisms to their evolutionary consequences: a primer. <i>Genetics</i>. Oxford
    University Press. <a href="https://doi.org/10.1093/genetics/iyae191">https://doi.org/10.1093/genetics/iyae191</a>'
  chicago: 'Grah, Rok, Calin C Guet, Gašper Tkačik, and Mato Lagator. “Linking Molecular
    Mechanisms to Their Evolutionary Consequences: A Primer.” <i>Genetics</i>. Oxford
    University Press, 2025. <a href="https://doi.org/10.1093/genetics/iyae191">https://doi.org/10.1093/genetics/iyae191</a>.'
  ieee: 'R. Grah, C. C. Guet, G. Tkačik, and M. Lagator, “Linking molecular mechanisms
    to their evolutionary consequences: a primer,” <i>Genetics</i>, vol. 229, no.
    2. Oxford University Press, 2025.'
  ista: 'Grah R, Guet CC, Tkačik G, Lagator M. 2025. Linking molecular mechanisms
    to their evolutionary consequences: a primer. Genetics. 229(2), iyae191.'
  mla: 'Grah, Rok, et al. “Linking Molecular Mechanisms to Their Evolutionary Consequences:
    A Primer.” <i>Genetics</i>, vol. 229, no. 2, iyae191, Oxford University Press,
    2025, doi:<a href="https://doi.org/10.1093/genetics/iyae191">10.1093/genetics/iyae191</a>.'
  short: R. Grah, C.C. Guet, G. Tkačik, M. Lagator, Genetics 229 (2025).
corr_author: '1'
date_created: 2025-01-29T08:21:35Z
date_published: 2025-02-01T00:00:00Z
date_updated: 2025-05-19T14:08:02Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1093/genetics/iyae191
external_id:
  isi:
  - '001379194200001'
  pmid:
  - '39601269'
file:
- access_level: open_access
  checksum: f730e416795969449ef49d97b82ac494
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  creator: dernst
  date_created: 2025-04-16T09:41:04Z
  date_updated: 2025-04-16T09:41:04Z
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has_accepted_license: '1'
intvolume: '       229'
isi: 1
issue: '2'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Genetics
publication_identifier:
  eissn:
  - 1943-2631
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Linking molecular mechanisms to their evolutionary consequences: a primer'
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: 229
year: '2025'
...