---
OA_place: publisher
OA_type: hybrid
_id: '20655'
abstract:
- lang: eng
  text: Traits that affect organismal fitness are often highly genetically variable.
    This genetic variation is vital for populations to adapt to their environments,
    but it is also surprising given that nature – after all – ‘selects’ the best genotypes
    at the expense of those that fall short. Explaining the extensive genetic variation
    of fitness‐related traits is thus a longstanding puzzle in evolutionary biology,
    with cascading implications for ecology, conservation, and human health. Balancing
    selection – an umbrella term for scenarios in which natural selection maintains
    genetic variation – is a century‐old explanation to resolve this puzzle that has
    gained recent momentum from genome‐scale methods for detecting it. Yet evaluating
    whether balancing selection can, in fact, resolve the puzzle is challenging, given
    the logistical constraints of distinguishing balancing selection from alternative
    hypotheses and the daunting collection of theoretical models that formally underpin
    this debate. Here, we track the development of balancing selection theory over
    the last century and provide an accessible review of this rich collection of models.
    We first outline the range of biological scenarios that can generate balancing
    selection. We then examine how fundamental features of genetic systems – non‐random
    mating between individuals, ploidy levels, genetic drift, linkage, and genetic
    architectures of traits – have been progressively incorporated into the theory.
    We end by linking these theoretical predictions to ongoing empirical efforts to
    understand the evolutionary processes that explain genetic variation.
acknowledgement: 'We thank Brian Charlesworth, Deborah Charlesworth, and Sally Otto
  for extensive comments and suggestions. We also thank Göran Arnqvist, Adam Eyre-Walker,
  Philip Hedrick, Jitka Polechová, and Henrique Teotónio for further helpful comments
  on the manuscript. This work was supported by a H2020 Marie Skłodowska-Curie COFUND
  Action fellowship (#101034413, to F. R.), the Birgitta Sintring Foundation (#S2024-0007,
  to M. K. Z.), the Research Council of Norway (302619, to D. G.), the Alexander von
  Humboldt Foundation (to H. K.), the Swiss National Science Foundation (#211549,
  to X. L. R.), the Swedish Research Council (#2022-03603, to CO; #2020-03123, to
  E. I. S.) and the European Research Council (ERC-2023-STG-#101117517, to C. O.).
  We are particularly grateful to the European Society for Evolutionary Biology for
  funding a Special Topics Network workshop (to T. C., H. K., E. I. S.), from which
  this review began. Open Access funding provided by Institute of Science and Technology
  Austria/KEMÖ.'
article_number: 804-825
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Filip
  full_name: Ruzicka, Filip
  id: 347955dd-57b0-11ee-9095-c28bdd368f4b
  last_name: Ruzicka
- first_name: Martyna K.
  full_name: Zwoinska, Martyna K.
  last_name: Zwoinska
- first_name: Debora
  full_name: Goedert, Debora
  last_name: Goedert
- first_name: Hanna
  full_name: Kokko, Hanna
  last_name: Kokko
- first_name: Xiang‐Yi
  full_name: Li Richter, Xiang‐Yi
  last_name: Li Richter
- first_name: Iain R.
  full_name: Moodie, Iain R.
  last_name: Moodie
- first_name: Sofie
  full_name: Nilén, Sofie
  last_name: Nilén
- first_name: Colin
  full_name: Olito, Colin
  last_name: Olito
- first_name: Erik I.
  full_name: Svensson, Erik I.
  last_name: Svensson
- first_name: Peter
  full_name: Czuppon, Peter
  last_name: Czuppon
- first_name: Tim
  full_name: Connallon, Tim
  last_name: Connallon
citation:
  ama: Ruzicka F, Zwoinska MK, Goedert D, et al. A century of theories of balancing
    selection. <i>Biological Reviews</i>. 2026;101(2). doi:<a href="https://doi.org/10.1111/brv.70103">10.1111/brv.70103</a>
  apa: Ruzicka, F., Zwoinska, M. K., Goedert, D., Kokko, H., Li Richter, X., Moodie,
    I. R., … Connallon, T. (2026). A century of theories of balancing selection. <i>Biological
    Reviews</i>. Wiley. <a href="https://doi.org/10.1111/brv.70103">https://doi.org/10.1111/brv.70103</a>
  chicago: Ruzicka, Filip, Martyna K. Zwoinska, Debora Goedert, Hanna Kokko, Xiang‐Yi
    Li Richter, Iain R. Moodie, Sofie Nilén, et al. “A Century of Theories of Balancing
    Selection.” <i>Biological Reviews</i>. Wiley, 2026. <a href="https://doi.org/10.1111/brv.70103">https://doi.org/10.1111/brv.70103</a>.
  ieee: F. Ruzicka <i>et al.</i>, “A century of theories of balancing selection,”
    <i>Biological Reviews</i>, vol. 101, no. 2. Wiley, 2026.
  ista: Ruzicka F, Zwoinska MK, Goedert D, Kokko H, Li Richter X, Moodie IR, Nilén
    S, Olito C, Svensson EI, Czuppon P, Connallon T. 2026. A century of theories of
    balancing selection. Biological Reviews. 101(2), 804–825.
  mla: Ruzicka, Filip, et al. “A Century of Theories of Balancing Selection.” <i>Biological
    Reviews</i>, vol. 101, no. 2, 804–825, Wiley, 2026, doi:<a href="https://doi.org/10.1111/brv.70103">10.1111/brv.70103</a>.
  short: F. Ruzicka, M.K. Zwoinska, D. Goedert, H. Kokko, X. Li Richter, I.R. Moodie,
    S. Nilén, C. Olito, E.I. Svensson, P. Czuppon, T. Connallon, Biological Reviews
    101 (2026).
corr_author: '1'
das_tickbox: '0'
date_created: 2025-11-19T09:43:50Z
date_published: 2026-04-01T00:00:00Z
date_updated: 2026-07-27T08:08:09Z
day: '01'
ddc:
- '570'
department:
- _id: BeVi
doi: 10.1111/brv.70103
ec_funded: 1
external_id:
  isi:
  - '001614285900001'
  pmid:
  - '41235821 '
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  date_created: 2026-07-27T08:07:35Z
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fulldoi: https://doi.org/10.1111/brv.70103
has_accepted_license: '1'
intvolume: '       101'
isi: 1
issue: '2'
keyword:
- evolutionary theory
- population genetics
- balancing selection
- heterozygote advantage
- trade-offs
- negative frequency-dependent selection
- fitness variation
- mathematical modelling
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
  call_identifier: H2020
  grant_number: '101034413'
  name: 'IST-BRIDGE: International postdoctoral program'
publication: Biological Reviews
publication_identifier:
  eissn:
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  issn:
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publisher: Wiley
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supplementarymaterial: yes
title: A century of theories of balancing selection
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...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22998'
abstract:
- lang: eng
  text: Balancing selection, a form of selection that maintains genetic diversity,
    is difficult to detect, and the importance of balancing selection for the maintenance
    of genetic variation may be larger than often assumed. We model the possibility
    that the diversity-promoting effects of balancing selection extend to other loci
    that show sign epistasis with a locus under balancing selection. Rather than focusing
    on overdominance, as was done in previous efforts, we explore the effects of negative
    frequency dependence and show that this has important effects on the conditions
    under which the diversity-promoting effect of epistasis can occur in diploids.
    Our results show that not only recombination rate but also the dominance of sign
    epistasis are key parameters that determine the maintenance of polymorphism beyond
    the locus under direct balancing selection. We suggest that the effect we explore
    may play a significant role, especially when balancing selection acts on major
    effect loci.
acknowledgement: This work was funded by grants from the Swedish Research Council
  (2023-03730 to G.A.) and the DOC fellowship from the Austrian Academy of Science
  (26293 to K.K.). We thank L. Rowe for valuable discussions.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Kseniia
  full_name: Khudiakova, Kseniia
  id: 4E6DC800-AE37-11E9-AC72-31CAE5697425
  last_name: Khudiakova
  orcid: 0000-0002-6246-1465
- 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: Göran
  full_name: Arnqvist, Göran
  last_name: Arnqvist
biorxivid: 1
citation:
  ama: Khudiakova K, Barton NH, Arnqvist G. Sign epistasis extends the effects of
    balancing selection on genetic diversity. <i>Theoretical Population Biology</i>.
    2026;172:48-55. doi:<a href="https://doi.org/10.1016/j.tpb.2026.09.001">10.1016/j.tpb.2026.09.001</a>
  apa: Khudiakova, K., Barton, N. H., &#38; Arnqvist, G. (2026). Sign epistasis extends
    the effects of balancing selection on genetic diversity. <i>Theoretical Population
    Biology</i>. <a href="https://doi.org/10.1016/j.tpb.2026.09.001">https://doi.org/10.1016/j.tpb.2026.09.001</a>
  chicago: Khudiakova, Kseniia, Nicholas H Barton, and Göran Arnqvist. “Sign Epistasis
    Extends the Effects of Balancing Selection on Genetic Diversity.” <i>Theoretical
    Population Biology</i>, 2026. <a href="https://doi.org/10.1016/j.tpb.2026.09.001">https://doi.org/10.1016/j.tpb.2026.09.001</a>.
  ieee: K. Khudiakova, N. H. Barton, and G. Arnqvist, “Sign epistasis extends the
    effects of balancing selection on genetic diversity,” <i>Theoretical Population
    Biology</i>, vol. 172. pp. 48–55, 2026.
  ista: Khudiakova K, Barton NH, Arnqvist G. 2026. Sign epistasis extends the effects
    of balancing selection on genetic diversity. Theoretical Population Biology. 172,
    48–55.
  mla: Khudiakova, Kseniia, et al. “Sign Epistasis Extends the Effects of Balancing
    Selection on Genetic Diversity.” <i>Theoretical Population Biology</i>, vol. 172,
    2026, pp. 48–55, doi:<a href="https://doi.org/10.1016/j.tpb.2026.09.001">10.1016/j.tpb.2026.09.001</a>.
  short: K. Khudiakova, N.H. Barton, G. Arnqvist, Theoretical Population Biology 172
    (2026) 48–55.
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: The Python code used for the numerical analyses is available
  online at https://github.com/khudyakovaks/Sign-epistasis-extends-the-effects-of-balancing-selection-on-genetic-diversity.
date_created: 2026-09-27T22:01:51Z
date_published: 2026-09-17T00:00:00Z
date_updated: 2026-10-07T06:38:02Z
day: '17'
ddc:
- '500'
- '570'
department:
- _id: JaMa
- _id: GradSch
- _id: NiBa
doi: 10.1016/j.tpb.2026.09.001
external_id:
  biorxivid:
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  pmid:
  - '42722132'
fulldoi: https://doi.org/10.1016/j.tpb.2026.09.001
has_accepted_license: '1'
intvolume: '       172'
keyword:
- Sign epistasis
- Balancing selection
- Within-population genetic variation
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
main_file_link:
- open_access: '1'
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  name: The impact of deleterious mutations on small populations
publication: Theoretical Population Biology
publication_identifier:
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  issn:
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publication_status: epub_ahead
quality_controlled: '1'
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supplementarymaterial: yes
title: Sign epistasis extends the effects of balancing selection on genetic diversity
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...