[{"author":[{"full_name":"Ruzicka, Filip","first_name":"Filip","id":"347955dd-57b0-11ee-9095-c28bdd368f4b","last_name":"Ruzicka"},{"last_name":"Zwoinska","first_name":"Martyna K.","full_name":"Zwoinska, Martyna K."},{"full_name":"Goedert, Debora","first_name":"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"},{"last_name":"Moodie","first_name":"Iain R.","full_name":"Moodie, Iain R."},{"last_name":"Nilén","full_name":"Nilén, Sofie","first_name":"Sofie"},{"last_name":"Olito","full_name":"Olito, Colin","first_name":"Colin"},{"full_name":"Svensson, Erik I.","first_name":"Erik I.","last_name":"Svensson"},{"last_name":"Czuppon","full_name":"Czuppon, Peter","first_name":"Peter"},{"first_name":"Tim","full_name":"Connallon, Tim","last_name":"Connallon"}],"supplementarymaterial":"yes","date_updated":"2026-07-27T08:08:09Z","OA_place":"publisher","issue":"2","license":"https://creativecommons.org/licenses/by-nc/4.0/","citation":{"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>.","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.","ieee":"F. Ruzicka <i>et al.</i>, “A century of theories of balancing selection,” <i>Biological Reviews</i>, vol. 101, no. 2. Wiley, 2026.","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).","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>","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>","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>."},"date_published":"2026-04-01T00:00:00Z","ddc":["570"],"das_tickbox":"0","month":"04","corr_author":"1","external_id":{"isi":["001614285900001"],"pmid":["41235821 "]},"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_type":"original","keyword":["evolutionary theory","population genetics","balancing selection","heterozygote advantage","trade-offs","negative frequency-dependent selection","fitness variation","mathematical modelling"],"date_created":"2025-11-19T09:43:50Z","language":[{"iso":"eng"}],"department":[{"_id":"BeVi"}],"file_date_updated":"2026-07-27T08:07:35Z","article_processing_charge":"Yes (via OA deal)","title":"A century of theories of balancing selection","publication_identifier":{"eissn":["1469-185X"],"issn":["1464-7931"]},"scopus_import":"1","quality_controlled":"1","file":[{"file_name":"2026_BiologicalReviews_Ruzicka.pdf","file_size":1757556,"access_level":"open_access","date_created":"2026-07-27T08:07:35Z","content_type":"application/pdf","file_id":"22409","success":1,"creator":"dernst","date_updated":"2026-07-27T08:07:35Z","checksum":"167d95cf0570d6e3653ab349b2a4355c","relation":"main_file"}],"oa":1,"volume":101,"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"}],"doi":"10.1111/brv.70103","project":[{"call_identifier":"H2020","grant_number":"101034413","name":"IST-BRIDGE: International postdoctoral program","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"publication":"Biological Reviews","_id":"20655","publication_status":"published","ec_funded":1,"year":"2026","type":"journal_article","publisher":"Wiley","oa_version":"Published Version","day":"01","researchdata_availability":"no","intvolume":"       101","article_number":"804-825","fulldoi":"https://doi.org/10.1111/brv.70103","OA_type":"hybrid","status":"public","has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"isi":1},{"oa":1,"alternative_title":["ISTA Thesis"],"file":[{"date_updated":"2025-05-11T22:30:04Z","relation":"source_file","checksum":"3e48b163c22114ef5d5371f758668289","embargo_to":"open_access","creator":"amrnjava","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"18551","date_created":"2024-11-13T12:15:28Z","file_size":26870629,"access_level":"closed","title":"Early stages of sex chromosome evolution","file_name":"AMrnjavac_thesis_library.docx"},{"embargo":"2025-05-11","content_type":"application/pdf","file_id":"18552","date_updated":"2025-05-11T22:30:04Z","relation":"main_file","checksum":"3ead60c1b678e7dcf018043aef3b5db2","creator":"amrnjava","file_size":4228766,"access_level":"open_access","file_name":"AMrnjavac_thesis_library.pdf","title":"Early stages of sex chromosome evolution","date_created":"2024-11-13T12:15:54Z"}],"tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication_status":"published","_id":"18531","abstract":[{"lang":"eng","text":"Sex chromosomes and autosomes exhibit very different evolutionary dynamics.\r\nThe Y chromosome usually degenerates, leaving many X-linked loci hemizygous in\r\nmales. Since recessive X-linked mutations are always exposed to selection in males,\r\nselection is more efficient on the X chromosome than on autosomes on recessive\r\nmutations, leading to faster adaptation on the X chromosome than other genomic\r\nregions, if beneficial mutations are on average recessive (known as the Faster-X\r\neffect). In the presence of the functional, but non-recombining gametolog on the Y (as\r\nis often the case in young non-recombining regions), recessive mutations are\r\nsheltered from selection on the X chromosome. We model this scenario and show that\r\nthe efficiency of selection is reduced on diploid X loci due to sheltering by the Y\r\nchromosome. Reduced efficiency of selection leads to slower adaptation and\r\nincreased accumulation of deleterious mutations (Slower-X effect). We extended this\r\nmodel to explore the effect of sex-specific selection on degeneration of sex\r\nchromosomes, showing theoretically that male-limited genes degenerate on the X\r\nchromosome and female-biased genes degenerate on the Y chromosome. This\r\nprediction depends on the effective population size and the mutation rate, explaining\r\nthe variety of sex chromosome degeneration patterns observed in nature.\r\nTo test for direct evidence of a Slower-X (or Slower-Z) effect, we analyzed the\r\nZW sex chromosomes of the flatworm Schistosoma japonicum, which have a very\r\nyoung non-recombining region with non-degenerated W. Diploid Z-linked genes have\r\nhigher ratios of non-synonymous to synonymous polymorphisms than autosomal\r\ngenes, supporting reduced efficiency of selection on the diploid Z region. These results\r\nprovide evidence of sheltering by the W chromosome, a mechanism that could\r\ncontribute to Z (X) chromosome degeneration, and illustrate contrasting evolutionary\r\npatterns in old and young sex chromosome regions. In addition, genes with sexspecific patterns of expression show opposite patterns of selection in the young\r\n(diploid) and old (hemizygous) Z, showing the complex manner in which sex-specific selection shapes the evolutionary patterns of sex chromosomes. "}],"doi":"10.15479/at:ista:18531","status":"public","fulldoi":"https://doi.org/10.15479/at:ista:18531","day":"11","researchdata_availability":"unclear","publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","type":"dissertation","year":"2024","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"CampIT"}],"has_accepted_license":"1","citation":{"apa":"Mrnjavac, A. (2024). <i>Early stages of sex chromosome evolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:18531\">https://doi.org/10.15479/at:ista:18531</a>","ama":"Mrnjavac A. Early stages of sex chromosome evolution. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:18531\">10.15479/at:ista:18531</a>","mla":"Mrnjavac, Andrea. <i>Early Stages of Sex Chromosome Evolution</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:18531\">10.15479/at:ista:18531</a>.","ista":"Mrnjavac A. 2024. Early stages of sex chromosome evolution. Institute of Science and Technology Austria.","chicago":"Mrnjavac, Andrea. “Early Stages of Sex Chromosome Evolution.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:18531\">https://doi.org/10.15479/at:ista:18531</a>.","ieee":"A. Mrnjavac, “Early stages of sex chromosome evolution,” Institute of Science and Technology Austria, 2024.","short":"A. Mrnjavac, Early Stages of Sex Chromosome Evolution, Institute of Science and Technology Austria, 2024."},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","OA_place":"publisher","date_updated":"2026-10-02T11:14:08Z","doi_confirm":"1","supplementarymaterial":"unclear","author":[{"last_name":"Mrnjavac","full_name":"Mrnjavac, Andrea","first_name":"Andrea","id":"353FAC84-AE61-11E9-8BFC-00D3E5697425"}],"page":"181","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"12521"},{"status":"public","id":"18549","relation":"part_of_dissertation"}]},"month":"11","degree_awarded":"PhD","ddc":["576"],"date_published":"2024-11-11T00:00:00Z","OA_embargo":"6","corr_author":"1","publication_identifier":{"issn":["2663-337X"]},"article_processing_charge":"No","title":"Early stages of sex chromosome evolution","department":[{"_id":"GradSch"},{"_id":"BeVi"}],"file_date_updated":"2025-05-11T22:30:04Z","language":[{"iso":"eng"}],"supervisor":[{"last_name":"Vicoso","full_name":"Vicoso, Beatriz","first_name":"Beatriz","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4579-8306"}],"date_created":"2024-11-11T08:40:45Z","keyword":["Sex chromosomes","evolution","selection","sheltering"]},{"fulldoi":"https://doi.org/10.15479/AT:ISTA:51","status":"public","day":"02","year":"2017","ec_funded":1,"type":"research_data","publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","file_date_updated":"2020-07-14T12:47:02Z","department":[{"_id":"KrCh"}],"datarep_id":"51","title":"Strong amplifiers of natural selection","article_processing_charge":"No","date_created":"2018-12-12T12:31:32Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","keyword":["natural selection"],"has_accepted_license":"1","citation":{"chicago":"Pavlogiannis, Andreas, Josef Tkadlec, Krishnendu Chatterjee, and Martin Nowak . “Strong Amplifiers of Natural Selection.” Institute of Science and Technology Austria, 2017. <a href=\"https://doi.org/10.15479/AT:ISTA:51\">https://doi.org/10.15479/AT:ISTA:51</a>.","ista":"Pavlogiannis A, Tkadlec J, Chatterjee K, Nowak  M. 2017. Strong amplifiers of natural selection, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:51\">10.15479/AT:ISTA:51</a>.","ieee":"A. Pavlogiannis, J. Tkadlec, K. Chatterjee, and M. Nowak , “Strong amplifiers of natural selection.” Institute of Science and Technology Austria, 2017.","short":"A. Pavlogiannis, J. Tkadlec, K. Chatterjee, M. Nowak , (2017).","apa":"Pavlogiannis, A., Tkadlec, J., Chatterjee, K., &#38; Nowak , M. (2017). Strong amplifiers of natural selection. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:51\">https://doi.org/10.15479/AT:ISTA:51</a>","mla":"Pavlogiannis, Andreas, et al. <i>Strong Amplifiers of Natural Selection</i>. Institute of Science and Technology Austria, 2017, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:51\">10.15479/AT:ISTA:51</a>.","ama":"Pavlogiannis A, Tkadlec J, Chatterjee K, Nowak  M. Strong amplifiers of natural selection. 2017. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:51\">10.15479/AT:ISTA:51</a>"},"date_updated":"2025-04-15T08:12:19Z","file":[{"date_created":"2018-12-12T13:05:18Z","access_level":"open_access","file_size":32987015,"file_name":"IST-2017-51-v1+2_illustration.mp4","checksum":"b427dd46a30096a1911b245640c47af8","date_updated":"2020-07-14T12:47:02Z","relation":"main_file","creator":"system","file_id":"5644","content_type":"video/mp4"}],"author":[{"last_name":"Pavlogiannis","orcid":"0000-0002-8943-0722","id":"49704004-F248-11E8-B48F-1D18A9856A87","first_name":"Andreas","full_name":"Pavlogiannis, Andreas"},{"orcid":"0000-0002-1097-9684","id":"3F24CCC8-F248-11E8-B48F-1D18A9856A87","full_name":"Tkadlec, Josef","first_name":"Josef","last_name":"Tkadlec"},{"last_name":"Chatterjee","orcid":"0000-0002-4561-241X","full_name":"Chatterjee, Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","first_name":"Krishnendu"},{"full_name":"Nowak , Martin","first_name":"Martin","last_name":"Nowak "}],"oa":1,"related_material":{"record":[{"relation":"research_paper","status":"public","id":"5452"},{"status":"public","id":"5751","relation":"research_paper"}]},"month":"01","_id":"5559","doi":"10.15479/AT:ISTA:51","abstract":[{"lang":"eng","text":"Strong amplifiers of natural selection"}],"date_published":"2017-01-02T00:00:00Z","ddc":["519"],"project":[{"_id":"2581B60A-B435-11E9-9278-68D0E5697425","name":"Quantitative Graph Games: Theory and Applications","grant_number":"279307","call_identifier":"FP7"}]},{"date_updated":"2026-07-30T14:56:13Z","author":[{"first_name":"David","id":"419049E2-F248-11E8-B48F-1D18A9856A87","full_name":"Field, David","orcid":"0000-0002-4014-8478","last_name":"Field"},{"id":"3153D6D4-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas","full_name":"Ellis, Thomas","orcid":"0000-0002-8511-0254","last_name":"Ellis"}],"citation":{"short":"D. Field, T. Ellis, (2016).","ieee":"D. Field and T. Ellis, “Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012.” Institute of Science and Technology Austria, 2016.","chicago":"Field, David, and Thomas Ellis. “Inference of Mating Patterns among Wild Snapdragons in a Natural Hybrid Zone in 2012.” Institute of Science and Technology Austria, 2016. <a href=\"https://doi.org/10.15479/AT:ISTA:37\">https://doi.org/10.15479/AT:ISTA:37</a>.","ista":"Field D, Ellis T. 2016. Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:37\">10.15479/AT:ISTA:37</a>.","mla":"Field, David, and Thomas Ellis. <i>Inference of Mating Patterns among Wild Snapdragons in a Natural Hybrid Zone in 2012</i>. Institute of Science and Technology Austria, 2016, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:37\">10.15479/AT:ISTA:37</a>.","ama":"Field D, Ellis T. Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012. 2016. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:37\">10.15479/AT:ISTA:37</a>","apa":"Field, D., &#38; Ellis, T. (2016). Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:37\">https://doi.org/10.15479/AT:ISTA:37</a>"},"license":"https://creativecommons.org/publicdomain/zero/1.0/","ddc":["576"],"date_published":"2016-02-19T00:00:00Z","month":"02","related_material":{"record":[{"status":"public","id":"1398","relation":"dissertation_contains"}]},"contributor":[{"last_name":"Barton","first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","contributor_type":"project_manager"}],"date_created":"2018-12-12T12:31:30Z","keyword":["paternity assignment","pedigree","matting patterns","assortative mating","Antirrhinum majus","frequency-dependent selection","plant-pollinator interaction"],"article_processing_charge":"No","title":"Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012","file_date_updated":"2020-07-14T12:47:01Z","department":[{"_id":"NiBa"}],"oa":1,"file":[{"date_created":"2018-12-12T13:03:02Z","access_level":"open_access","file_size":132808,"file_name":"IST-2016-37-v1+1_paternity_archive.zip","checksum":"4ae751b1fa4897fa216241f975a57313","relation":"main_file","date_updated":"2020-07-14T12:47:01Z","creator":"system","content_type":"application/zip","file_id":"5620"}],"_id":"5553","tmp":{"short":"CC0 (1.0)","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","image":"/images/cc_0.png","name":"Creative Commons Public Domain Dedication (CC0 1.0)"},"abstract":[{"text":"Genotypic, phenotypic and demographic data for 2128 wild snapdragons and 1127 open-pollinated progeny from a natural hybrid zone, collected as part of Tom Ellis' PhD thesis (submitted) February 2016).\r\n\r\nTissue samples were sent to LGC Genomics in Berlin for DNA extraction, and genotyping at 70 SNP markers by KASPR genotyping. 29 of these SNPs failed to amplify reliably, and have been removed from this dataset.\r\n\r\nOther data were retreived from an online database of this population at www.antspec.org.","lang":"eng"}],"doi":"10.15479/AT:ISTA:37","day":"19","oa_version":"Published Version","publisher":"Institute of Science and Technology Austria","type":"research_data","year":"2016","status":"public","fulldoi":"https://doi.org/10.15479/AT:ISTA:37","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","datarep_id":"37"},{"_id":"10899","publication":"Encyclopedia of Biodiversity","publication_status":"published","doi":"10.1016/b978-0-12-384719-5.00031-9","date_published":"2013-01-01T00:00:00Z","page":"508-515","month":"01","date_updated":"2024-10-09T21:02:37Z","edition":"2","author":[{"last_name":"Barton","orcid":"0000-0002-8548-5240","first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H"}],"quality_controlled":"1","citation":{"apa":"Barton, N. H. (2013). Differentiation. In <i>Encyclopedia of Biodiversity</i> (2nd ed., pp. 508–515). Elsevier. <a href=\"https://doi.org/10.1016/b978-0-12-384719-5.00031-9\">https://doi.org/10.1016/b978-0-12-384719-5.00031-9</a>","ama":"Barton NH. Differentiation. In: <i>Encyclopedia of Biodiversity</i>. 2nd ed. Elsevier; 2013:508-515. doi:<a href=\"https://doi.org/10.1016/b978-0-12-384719-5.00031-9\">10.1016/b978-0-12-384719-5.00031-9</a>","mla":"Barton, Nicholas H. “Differentiation.” <i>Encyclopedia of Biodiversity</i>, 2nd ed., Elsevier, 2013, pp. 508–15, doi:<a href=\"https://doi.org/10.1016/b978-0-12-384719-5.00031-9\">10.1016/b978-0-12-384719-5.00031-9</a>.","ieee":"N. H. Barton, “Differentiation,” in <i>Encyclopedia of Biodiversity</i>, 2nd ed., Elsevier, 2013, pp. 508–515.","ista":"Barton NH. 2013.Differentiation. In: Encyclopedia of Biodiversity. , 508–515.","chicago":"Barton, Nicholas H. “Differentiation.” In <i>Encyclopedia of Biodiversity</i>, 2nd ed., 508–15. Elsevier, 2013. <a href=\"https://doi.org/10.1016/b978-0-12-384719-5.00031-9\">https://doi.org/10.1016/b978-0-12-384719-5.00031-9</a>.","short":"N.H. Barton, in:, Encyclopedia of Biodiversity, 2nd ed., Elsevier, 2013, pp. 508–515."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"date_created":"2022-03-21T07:46:22Z","keyword":["Adaptive landscape","Cline","Coalescent process","Gene flow","Hybrid zone","Local adaptation","Natural selection","Neutral theory","Population structure","Speciation"],"scopus_import":"1","publication_identifier":{"isbn":["978-0-12-384720-1"]},"title":"Differentiation","article_processing_charge":"No","department":[{"_id":"NiBa"}],"day":"01","publisher":"Elsevier","corr_author":"1","oa_version":"None","type":"book_chapter","year":"2013","status":"public","fulldoi":"https://doi.org/10.1016/b978-0-12-384719-5.00031-9"},{"day":"21","type":"journal_article","year":"2006","publisher":"Elsevier","oa_version":"None","fulldoi":"https://doi.org/10.1016/j.jtbi.2005.10.020","OA_type":"closed access","status":"public","intvolume":"       240","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","pmid":1,"volume":240,"quality_controlled":"1","_id":"869","publication":"Journal of Theoretical Biology","publication_status":"published","abstract":[{"text":"The impact of synonymous nucleotide substitutions on fitness in mammals remains controversial. Despite some indications of selective constraint, synonymous sites are often assumed to be neutral, and the rate of their evolution is used as a proxy for mutation rate. We subdivide all sites into four classes in terms of the mutable CpG context, nonCpG, postC, preG, and postCpreG, and compare four-fold synonymous sites and intron sites residing outside transposable elements. The distribution of the rate of evolution across all synonymous sites is trimodal. Rate of evolution at nonCpG synonymous sites, not preceded by C and not followed by G, is ∼10% below that at such intron sites. In contrast, rate of evolution at postCpreG synonymous sites is ∼30% above that at such intron sites. Finally, synonymous and intron postC and preG sites evolve at similar rates. The relationship between the levels of polymorphism at the corresponding synonymous and intron sites is very similar to that between their rates of evolution. Within every class, synonymous sites are occupied by G or C much more often than intron sites, whose nucleotide composition is consistent with neutral mutation-drift equilibrium. These patterns suggest that synonymous sites are under weak selection in favor of G and C, with the average coefficient s∼0.25/Ne∼10-5, where Ne is the effective population size. Such selection decelerates evolution and reduces variability at sites with symmetric mutation, but has the opposite effects at sites where the favored nucleotides are more mutable. The amino-acid composition of proteins dictates that many synonymous sites are CpGprone, which causes them, on average, to evolve faster and to be more polymorphic than intron sites. An average genotype carries ∼107 suboptimal nucleotides at synonymous sites, implying synergistic epistasis in selection against them.","lang":"eng"}],"doi":"10.1016/j.jtbi.2005.10.020","acknowledgement":"This research was supported in part by the Intramural Research Program of the NIH, National Library of Medicine.","external_id":{"pmid":["16343547"]},"article_type":"original","date_created":"2018-12-11T11:48:56Z","language":[{"iso":"eng"}],"extern":"1","keyword":["Mutation","Selection","Synonymous site","Evolution","Genetic drift"],"publication_identifier":{"issn":["1095-8541"]},"scopus_import":"1","title":"Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites","article_processing_charge":"No","date_updated":"2026-05-08T10:18:03Z","author":[{"orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor","full_name":"Kondrashov, Fyodor","last_name":"Kondrashov"},{"last_name":"Ogurtsov","first_name":"Aleksey","full_name":"Ogurtsov, Aleksey"},{"full_name":"Kondrashov, Alexey","first_name":"Alexey","last_name":"Kondrashov"}],"citation":{"apa":"Kondrashov, F., Ogurtsov, A., &#38; Kondrashov, A. (2006). Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites. <i>Journal of Theoretical Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jtbi.2005.10.020\">https://doi.org/10.1016/j.jtbi.2005.10.020</a>","mla":"Kondrashov, Fyodor, et al. “Selection in Favor of Nucleotides G and C Diversifies Evolution Rates and Levels of Polymorphism at Mammalian Synonymous Sites.” <i>Journal of Theoretical Biology</i>, vol. 240, no. 4, Elsevier, 2006, pp. 616–26, doi:<a href=\"https://doi.org/10.1016/j.jtbi.2005.10.020\">10.1016/j.jtbi.2005.10.020</a>.","ama":"Kondrashov F, Ogurtsov A, Kondrashov A. Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites. <i>Journal of Theoretical Biology</i>. 2006;240(4):616-626. doi:<a href=\"https://doi.org/10.1016/j.jtbi.2005.10.020\">10.1016/j.jtbi.2005.10.020</a>","ieee":"F. Kondrashov, A. Ogurtsov, and A. Kondrashov, “Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites,” <i>Journal of Theoretical Biology</i>, vol. 240, no. 4. Elsevier, pp. 616–626, 2006.","chicago":"Kondrashov, Fyodor, Aleksey Ogurtsov, and Alexey Kondrashov. “Selection in Favor of Nucleotides G and C Diversifies Evolution Rates and Levels of Polymorphism at Mammalian Synonymous Sites.” <i>Journal of Theoretical Biology</i>. Elsevier, 2006. <a href=\"https://doi.org/10.1016/j.jtbi.2005.10.020\">https://doi.org/10.1016/j.jtbi.2005.10.020</a>.","ista":"Kondrashov F, Ogurtsov A, Kondrashov A. 2006. Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites. Journal of Theoretical Biology. 240(4), 616–626.","short":"F. Kondrashov, A. Ogurtsov, A. Kondrashov, Journal of Theoretical Biology 240 (2006) 616–626."},"issue":"4","date_published":"2006-06-21T00:00:00Z","publist_id":"6779","month":"06","page":"616 - 626"}]