[{"pmid":1,"publication_status":"published","OA_type":"hybrid","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"oa_version":"Published Version","title":"A century of theories of balancing selection","fulldoi":"https://doi.org/10.1111/brv.70103","article_number":"804-825","_id":"20655","citation":{"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).","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>.","ieee":"F. Ruzicka <i>et al.</i>, “A century of theories of balancing selection,” <i>Biological Reviews</i>, vol. 101, no. 2. Wiley, 2026.","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>","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.","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>.","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>"},"file_date_updated":"2026-07-27T08:07:35Z","ec_funded":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","keyword":["evolutionary theory","population genetics","balancing selection","heterozygote advantage","trade-offs","negative frequency-dependent selection","fitness variation","mathematical modelling"],"day":"01","issue":"2","month":"04","file":[{"content_type":"application/pdf","relation":"main_file","date_updated":"2026-07-27T08:07:35Z","file_name":"2026_BiologicalReviews_Ruzicka.pdf","access_level":"open_access","date_created":"2026-07-27T08:07:35Z","file_id":"22409","file_size":1757556,"success":1,"creator":"dernst","checksum":"167d95cf0570d6e3653ab349b2a4355c"}],"supplementarymaterial":"yes","publication_identifier":{"eissn":["1469-185X"],"issn":["1464-7931"]},"date_created":"2025-11-19T09:43:50Z","status":"public","das_tickbox":"0","language":[{"iso":"eng"}],"doi":"10.1111/brv.70103","article_type":"original","external_id":{"pmid":["41235821 "],"isi":["001614285900001"]},"researchdata_availability":"no","oa":1,"project":[{"grant_number":"101034413","call_identifier":"H2020","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c","name":"IST-BRIDGE: International postdoctoral program"}],"isi":1,"year":"2026","date_updated":"2026-07-27T08:08:09Z","author":[{"full_name":"Ruzicka, Filip","first_name":"Filip","last_name":"Ruzicka","id":"347955dd-57b0-11ee-9095-c28bdd368f4b"},{"full_name":"Zwoinska, Martyna K.","first_name":"Martyna K.","last_name":"Zwoinska"},{"full_name":"Goedert, Debora","first_name":"Debora","last_name":"Goedert"},{"first_name":"Hanna","full_name":"Kokko, Hanna","last_name":"Kokko"},{"last_name":"Li Richter","first_name":"Xiang‐Yi","full_name":"Li Richter, Xiang‐Yi"},{"full_name":"Moodie, Iain R.","first_name":"Iain R.","last_name":"Moodie"},{"full_name":"Nilén, Sofie","first_name":"Sofie","last_name":"Nilén"},{"last_name":"Olito","full_name":"Olito, Colin","first_name":"Colin"},{"full_name":"Svensson, Erik I.","first_name":"Erik I.","last_name":"Svensson"},{"first_name":"Peter","full_name":"Czuppon, Peter","last_name":"Czuppon"},{"last_name":"Connallon","full_name":"Connallon, Tim","first_name":"Tim"}],"type":"journal_article","scopus_import":"1","volume":101,"department":[{"_id":"BeVi"}],"article_processing_charge":"Yes (via OA deal)","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.","ddc":["570"],"quality_controlled":"1","license":"https://creativecommons.org/licenses/by-nc/4.0/","corr_author":"1","has_accepted_license":"1","OA_place":"publisher","date_published":"2026-04-01T00:00:00Z","publication":"Biological Reviews","intvolume":"       101","publisher":"Wiley","abstract":[{"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.","lang":"eng"}]},{"year":"2026","date_updated":"2026-10-07T06:38:02Z","author":[{"full_name":"Khudiakova, Kseniia","first_name":"Kseniia","last_name":"Khudiakova","orcid":"0000-0002-6246-1465","id":"4E6DC800-AE37-11E9-AC72-31CAE5697425"},{"first_name":"Nicholas H","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Göran","full_name":"Arnqvist, Göran","last_name":"Arnqvist"}],"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.","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.tpb.2026.09.001"}],"volume":172,"department":[{"_id":"JaMa"},{"_id":"GradSch"},{"_id":"NiBa"}],"related_material":{"record":[{"relation":"earlier_version","status":"public","id":"21968"}]},"type":"journal_article","scopus_import":"1","PlanS_conform":"1","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)","corr_author":"1","has_accepted_license":"1","ddc":["500","570"],"quality_controlled":"1","date_published":"2026-09-17T00:00:00Z","OA_place":"publisher","publication":"Theoretical Population Biology","intvolume":"       172","biorxivid":1,"abstract":[{"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.","lang":"eng"}],"oa_version":"Published Version","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publication_status":"epub_ahead","pmid":1,"OA_type":"hybrid","title":"Sign epistasis extends the effects of balancing selection on genetic diversity","fulldoi":"https://doi.org/10.1016/j.tpb.2026.09.001","_id":"22998","keyword":["Sign epistasis","Balancing selection","Within-population genetic variation"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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.","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>","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.","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>","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>."},"day":"17","month":"09","publication_identifier":{"eissn":["1096-0325"],"issn":["0040-5809"]},"date_created":"2026-09-27T22:01:51Z","das_tickbox":"1","status":"public","supplementarymaterial":"yes","doi":"10.1016/j.tpb.2026.09.001","article_type":"original","language":[{"iso":"eng"}],"project":[{"grant_number":"26293","_id":"34d33d68-11ca-11ed-8bc3-ec13763c0ca8","name":"The impact of deleterious mutations on small populations"}],"page":"48-55","external_id":{"biorxivid":["10.1101/2025.04.09.647826"],"pmid":["42722132"]},"researchdata_availability":"no","oa":1}]