Section: Evolutionary Biology
Topic: Evolution, Genetics/Genomics, Population biology

Balancing selection at a wing pattern locus is associated with major shifts in genome-wide patterns of diversity and gene flow

10.24072/pcjournal.298 - Peer Community Journal, Volume 3 (2023), article no. e65.

Get full text PDF Peer reviewed and recommended by PCI
article image

Selection shapes genetic diversity around target mutations, yet little is known about how selection on specific loci affects the genetic trajectories of populations, including their genome-wide patterns of diversity and demographic responses. Here we study the patterns of genetic variation and geographic structure in a neotropical butterfly, Heliconius numata, and its closely related allies in the so-called melpomene-silvaniform clade. H. numata is known to have evolved an inversion supergene which controls variation in wing patterns involved in mimicry associations with distinct groups of co-mimics whereas it is associated to disassortative mate preferences and heterozygote advantage at this locus. We contrasted patterns of genetic diversity and structure 1) among extant polymorphic and monomorphic populations of H. numata, 2) between H. numata and its close relatives, and 3) between ancestral lineages. We show that H. numata populations which carry the inversions as a balanced polymorphism show markedly distinct patterns of diversity compared to all other taxa. They show the highest genetic diversity and effective population size estimates in the entire clade, as well as a low level of geographic structure and isolation by distance across the entire Amazon basin. By contrast, monomorphic populations of H. numata as well as its sister species and their ancestral lineages all show lower effective population sizes and genetic diversity, and higher levels of geographical structure across the continent. One hypothesis is that the large effective population size of polymorphic populations could be caused by the shift to a regime of balancing selection due to the genetic load and disassortative preferences associated with inversions. Testing this hypothesis with forward simulations supported the observation of increased diversity in populations with the supergene. Our results are consistent with the hypothesis that the formation of the supergene triggered a change in gene flow, causing a general increase in genetic diversity and the homogenisation of genomes at the continental scale.

Published online:
DOI: 10.24072/pcjournal.298
Type: Research article
Keywords: balancing selection, gene flow, supergene, mimetism, inversion

Rodríguez de Cara, María Ángeles 1; Jay, Paul 1; Rougemont, Quentin 1; Chouteau, Mathieu 1, 2; Whibley, Annabel 3, 4; Huber, Barbara 5; Piron-Prunier, Florence 3; Ramos, Renato Rogner 6; Freitas, André V. L. 6; Salazar, Camilo 7; Silva-Brandão, Karina Lucas 8; Torres, Tatiana Teixeira 9; Joron, Mathieu 1

1 Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Univ Montpellier, CNRS, EPHE, IRD, Montpellier, France
2 Laboratoire Ecologie, Evolution, Interactions Des Systèmes Amazoniens (LEEISA), Université de Guyane, IFREMER, CNRS, Cayenne, Guyane Française
3 Institut de Systématique Evolution Biodiversité (ISYEB), Museum National d’Histoire Naturelle, CNRS, Sorbonne-Université, EPHE, Université des Antilles, Paris, France
4 School of Biological Sciences, University of Auckland, Auckland, New Zealand
5 Instituto de Ciencias Ecológicas y Ambientales (ICAE), Univ de los Andes, Mérida, Venezuela
6 Departamento de Biologia Animal, Instituto de Biologia, Unicamp, Campinas, São Paulo, Brazil
7 Department of Biology, Faculty of Natural Sciences, Universidad del Rosario, Carrera 24 No 63C- 69, Bogotá 111221, Colombia
8 Museum of Nature Hamburg, Leibniz Institute for the Analysis of Biodiversity Change. Martin-Luther-King-Platz 3, 20146 Hamburg, Germany
9 Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo (USP), São Paulo, Brazil
License: CC-BY 4.0
Copyrights: The authors retain unrestricted copyrights and publishing rights
     author = {Rodr{\'\i}guez de Cara, Mar{\'\i}a \'Angeles and Jay, Paul and Rougemont, Quentin and Chouteau, Mathieu and Whibley, Annabel and Huber, Barbara and Piron-Prunier, Florence and Ramos, Renato Rogner and Freitas, Andr\'e V. L. and Salazar, Camilo and Silva-Brand\~ao, Karina Lucas and Torres, Tatiana Teixeira and Joron, Mathieu},
     title = {Balancing selection at a wing pattern locus is associated with major shifts in genome-wide patterns of diversity and gene flow},
     journal = {Peer Community Journal},
     eid = {e65},
     publisher = {Peer Community In},
     volume = {3},
     year = {2023},
     doi = {10.24072/pcjournal.298},
     language = {en},
     url = {}
AU  - Rodríguez de Cara, María Ángeles
AU  - Jay, Paul
AU  - Rougemont, Quentin
AU  - Chouteau, Mathieu
AU  - Whibley, Annabel
AU  - Huber, Barbara
AU  - Piron-Prunier, Florence
AU  - Ramos, Renato Rogner
AU  - Freitas, André V. L.
AU  - Salazar, Camilo
AU  - Silva-Brandão, Karina Lucas
AU  - Torres, Tatiana Teixeira
AU  - Joron, Mathieu
TI  - Balancing selection at a wing pattern locus is associated with major shifts in genome-wide patterns of diversity and gene flow
JO  - Peer Community Journal
PY  - 2023
VL  - 3
PB  - Peer Community In
UR  -
DO  - 10.24072/pcjournal.298
LA  - en
ID  - 10_24072_pcjournal_298
ER  - 
%0 Journal Article
%A Rodríguez de Cara, María Ángeles
%A Jay, Paul
%A Rougemont, Quentin
%A Chouteau, Mathieu
%A Whibley, Annabel
%A Huber, Barbara
%A Piron-Prunier, Florence
%A Ramos, Renato Rogner
%A Freitas, André V. L.
%A Salazar, Camilo
%A Silva-Brandão, Karina Lucas
%A Torres, Tatiana Teixeira
%A Joron, Mathieu
%T Balancing selection at a wing pattern locus is associated with major shifts in genome-wide patterns of diversity and gene flow
%J Peer Community Journal
%D 2023
%V 3
%I Peer Community In
%R 10.24072/pcjournal.298
%G en
%F 10_24072_pcjournal_298
Rodríguez de Cara, María Ángeles; Jay, Paul; Rougemont, Quentin; Chouteau, Mathieu; Whibley, Annabel; Huber, Barbara; Piron-Prunier, Florence; Ramos, Renato Rogner; Freitas, André V. L.; Salazar, Camilo; Silva-Brandão, Karina Lucas; Torres, Tatiana Teixeira; Joron, Mathieu. Balancing selection at a wing pattern locus is associated with major shifts in genome-wide patterns of diversity and gene flow. Peer Community Journal, Volume 3 (2023), article  no. e65. doi : 10.24072/pcjournal.298.

PCI peer reviews and recommendation, and links to data, scripts, code and supplementary information: 10.24072/pci.evolbiol.100522

Conflict of interest of the recommender and peer reviewers:
The recommender in charge of the evaluation of the article and the reviewers declared that they have no conflict of interest (as defined in the code of conduct of PCI) with the authors or with the content of the article.

[1] Alexander, D. H.; Lange, K. Enhancements to the ADMIXTURE algorithm for individual ancestry estimation, BMC Bioinformatics, Volume 12 (2011) no. 1 | DOI

[2] Alexander, D. H.; Novembre, J.; Lange, K. Fast model-based estimation of ancestry in unrelated individuals, Genome Research, Volume 19 (2009) no. 9, pp. 1655-1664 | DOI

[3] Beichman, A. C.; Huerta-Sanchez, E.; Lohmueller, K. E. Using Genomic Data to Infer Historic Population Dynamics of Nonmodel Organisms, Annual Review of Ecology, Evolution, and Systematics, Volume 49 (2018) no. 1, pp. 433-456 | DOI

[4] Benson, G. Tandem repeats finder: a program to analyze DNA sequences, Nucleic Acids Research, Volume 27 (1999) no. 2, pp. 573-580 | DOI

[5] Brown, K. Ecologia Geográfica e Evolução nas Florestas Neotropicais. – Univ. Estadual de Campinas, Campinas, Brazil (1979) (

[6] Brown, K. S.; Benson, W. W. Adaptive Polymorphism Associated with Multiple Mullerian Mimicry in Heliconius numata (Lepid. Nymph.), Biotropica, Volume 6 (1974) no. 4 | DOI

[7] Chamberlain, N. L.; Hill, R. I.; Kapan, D. D.; Gilbert, L. E.; Kronforst, M. R. Polymorphic Butterfly Reveals the Missing Link in Ecological Speciation, Science, Volume 326 (2009) no. 5954, pp. 847-850 | DOI

[8] Chang, C. C.; Chow, C. C.; Tellier, L. C.; Vattikuti, S.; Purcell, S. M.; Lee, J. J. Second-generation PLINK: rising to the challenge of larger and richer datasets, GigaScience, Volume 4 (2015) no. 1 | DOI

[9] Charlesworth, B. Effective population size and patterns of molecular evolution and variation, Nature Reviews Genetics, Volume 10 (2009) no. 3, pp. 195-205 | DOI

[10] Chouteau, M.; Arias, M.; Joron, M. Warning signals are under positive frequency-dependent selection in nature, Proceedings of the National Academy of Sciences, Volume 113 (2016) no. 8, pp. 2164-2169 | DOI

[11] Chouteau, M.; Llaurens, V.; Piron-Prunier, F.; Joron, M. Polymorphism at a mimicry supergene maintained by opposing frequency-dependent selection pressures, Proceedings of the National Academy of Sciences, Volume 114 (2017) no. 31, pp. 8325-8329 | DOI

[12] Davey, J. W.; Chouteau, M.; Barker, S. L.; Maroja, L.; Baxter, S. W.; Simpson, F.; Merrill, R. M.; Joron, M.; Mallet, J.; Dasmahapatra, K. K.; Jiggins, C. D. Major Improvements to the Heliconius melpomene Genome Assembly Used to Confirm 10 Chromosome Fusion Events in 6 Million Years of Butterfly Evolution, G3 Genes|Genomes|Genetics, Volume 6 (2016) no. 3, pp. 695-708 | DOI

[13] DePristo, M. A.; Banks, E.; Poplin, R.; Garimella, K. V.; Maguire, J. R.; Hartl, C.; Philippakis, A. A.; del Angel, G.; Rivas, M. A.; Hanna, M.; McKenna, A.; Fennell, T. J.; Kernytsky, A. M.; Sivachenko, A. Y.; Cibulskis, K.; Gabriel, S. B.; Altshuler, D.; Daly, M. J. A framework for variation discovery and genotyping using next-generation DNA sequencing data, Nature Genetics, Volume 43 (2011) no. 5, pp. 491-498 | DOI

[14] Eckert, C. G.; Samis, K. E.; Lougheed, S. C. Genetic variation across species’ geographical ranges: the central–marginal hypothesis and beyond, Molecular Ecology, Volume 17 (2008) no. 5, pp. 1170-1188 | DOI

[15] Edelman, N. B.; Frandsen, P. B.; Miyagi, M.; Clavijo, B.; Davey, J.; Dikow, R. B.; García-Accinelli, G.; Van Belleghem, S. M.; Patterson, N.; Neafsey, D. E.; Challis, R.; Kumar, S.; Moreira, G. R. P.; Salazar, C.; Chouteau, M.; Counterman, B. A.; Papa, R.; Blaxter, M.; Reed, R. D.; Dasmahapatra, K. K.; Kronforst, M.; Joron, M.; Jiggins, C. D.; McMillan, W. O.; Di Palma, F.; Blumberg, A. J.; Wakeley, J.; Jaffe, D.; Mallet, J. Genomic architecture and introgression shape a butterfly radiation, Science, Volume 366 (2019) no. 6465, pp. 594-599 | DOI

[16] Emsley, M. G. Speciation in Heliconius (Lep., Nymphalidae): Morphology and geographic distribution, Zoologica : scientific contributions of the New York Zoological Society., Volume 50 (1965) no. 14, pp. 191-254 | DOI

[17] Faria, R.; Johannesson, K.; Butlin, R. K.; Westram, A. M. Evolving Inversions, Trends in Ecology & Evolution, Volume 34 (2019) no. 3, pp. 239-248 | DOI

[18] Freedman, A. H.; Gronau, I.; Schweizer, R. M.; Ortega-Del Vecchyo, D.; Han, E.; Silva, P. M.; Galaverni, M.; Fan, Z.; Marx, P.; Lorente-Galdos, B.; Beale, H.; Ramirez, O.; Hormozdiari, F.; Alkan, C.; Vilà, C.; Squire, K.; Geffen, E.; Kusak, J.; Boyko, A. R.; Parker, H. G.; Lee, C.; Tadigotla, V.; Siepel, A.; Bustamante, C. D.; Harkins, T. T.; Nelson, S. F.; Ostrander, E. A.; Marques-Bonet, T.; Wayne, R. K.; Novembre, J. Genome Sequencing Highlights the Dynamic Early History of Dogs, PLoS Genetics, Volume 10 (2014) no. 1 | DOI

[19] Glinka, S.; Ometto, L.; Mousset, S.; Stephan, W.; De Lorenzo, D. Demography and Natural Selection Have Shaped Genetic Variation in Drosophila melanogaster: A Multi-locus Approach, Genetics, Volume 165 (2003) no. 3, pp. 1269-1278 | DOI

[20] Gronau, I.; Hubisz, M. J.; Gulko, B.; Danko, C. G.; Siepel, A. Bayesian inference of ancient human demography from individual genome sequences, Nature Genetics, Volume 43 (2011) no. 10, pp. 1031-1034 | DOI

[21] Gutenkunst, R. N.; Hernandez, R. D.; Williamson, S. H.; Bustamante, C. D. Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency Data, PLoS Genetics, Volume 5 (2009) no. 10 | DOI

[22] Hackenberg, M.; Previti, C.; Luque-Escamilla, P. L.; Carpena, P.; Martínez-Aroza, J.; Oliver, J. L. CpGcluster: a distance-based algorithm for CpG-island detection, BMC Bioinformatics, Volume 7 (2006) no. 1 | DOI

[23] Haller, B. C.; Messer, P. W. SLiM 3: Forward Genetic Simulations Beyond the Wright–Fisher Model, Molecular Biology and Evolution, Volume 36 (2019) no. 3, pp. 632-637 | DOI

[24] Hedrick, P. W.; Tuttle, E. M.; Gonser, R. A. Negative-Assortative Mating in the White-Throated Sparrow, Journal of Heredity, Volume 109 (2017) no. 3, pp. 223-231 | DOI

[25] Jay, P.; Chouteau, M.; Whibley, A.; Bastide, H.; Parrinello, H.; Llaurens, V.; Joron, M. Mutation load at a mimicry supergene sheds new light on the evolution of inversion polymorphisms, Nature Genetics, Volume 53 (2021) no. 3, pp. 288-293 | DOI

[26] Jay, P.; Whibley, A.; Frézal, L.; Rodríguez de Cara, M. Á.; Nowell, R. W.; Mallet, J.; Dasmahapatra, K. K.; Joron, M. Supergene Evolution Triggered by the Introgression of a Chromosomal Inversion, Current Biology, Volume 28 (2018) no. 11 | DOI

[27] Jiggins, C. Is genetic diversity enhanced by a supergene?, Peer Community in Evolutionary Biology (2023) | DOI

[28] Jiggins, C. D.; Estrada, C.; Rodrigues, A. Mimicry and the evolution of premating isolation in Heliconius melpomene Linnaeus, Journal of Evolutionary Biology, Volume 17 (2004) no. 3, pp. 680-691 | DOI

[29] Jiggins, C. D.; Naisbit, R. E.; Coe, R. L.; Mallet, J. Reproductive isolation caused by colour pattern mimicry, Nature, Volume 411 (2001) no. 6835, pp. 302-305 | DOI

[30] Joron, M.; Frezal, L.; Jones, R. T.; Chamberlain, N. L.; Lee, S. F.; Haag, C. R.; Whibley, A.; Becuwe, M.; Baxter, S. W.; Ferguson, L.; Wilkinson, P. A.; Salazar, C.; Davidson, C.; Clark, R.; Quail, M. A.; Beasley, H.; Glithero, R.; Lloyd, C.; Sims, S.; Jones, M. C.; Rogers, J.; Jiggins, C. D.; ffrench-Constant, R. H. Chromosomal rearrangements maintain a polymorphic supergene controlling butterfly mimicry, Nature, Volume 477 (2011) no. 7363, pp. 203-206 | DOI

[31] Joron, M.; Papa, R.; Beltrán, M.; Chamberlain, N.; Mavárez, J.; Baxter, S.; Abanto, M.; Bermingham, E.; Humphray, S. J.; Rogers, J.; Beasley, H.; Barlow, K.; H. ffrench-Constant, R.; Mallet, J.; McMillan, W. O.; Jiggins, C. D. A Conserved Supergene Locus Controls Colour Pattern Diversity in Heliconius Butterflies, PLoS Biology, Volume 4 (2006) no. 10 | DOI

[32] Joron, M.; Wynne, I. R.; Lamas, G.; Mallet, J. Variable Selection and the Coexistence of Multiple mimetic forms of the Butterfly Heliconius numata, Evolutionary Ecology, Volume 13 (1999) no. 7-8, pp. 721-754 | DOI

[33] Knoppien, P. Rare male mating advantage: a review, Biological Reviews, Volume 60 (1985) no. 1, pp. 81-117 | DOI

[34] Kozak, K. M.; Wahlberg, N.; Neild, A. F. E.; Dasmahapatra, K. K.; Mallet, J.; Jiggins, C. D. Multilocus Species Trees Show the Recent Adaptive Radiation of the Mimetic Heliconius Butterflies, Systematic Biology, Volume 64 (2015) no. 3, pp. 505-524 | DOI

[35] Le Poul, Y.; Whibley, A.; Chouteau, M.; Prunier, F.; Llaurens, V.; Joron, M. Evolution of dominance mechanisms at a butterfly mimicry supergene, Nature Communications, Volume 5 (2014) no. 1 | DOI

[36] Lenth, R. V. Least-Squares Means: The R Package lsmeans, Journal of Statistical Software, Volume 69 (2016) no. 1 | DOI

[37] Li, H.; Handsaker, B.; Wysoker, A.; Fennell, T.; Ruan, J.; Homer, N.; Marth, G.; Abecasis, G.; Durbin, R. The Sequence Alignment/Map format and SAMtools, Bioinformatics, Volume 25 (2009) no. 16, pp. 2078-2079 | DOI

[38] Lunter, G.; Goodson, M. Stampy: A statistical algorithm for sensitive and fast mapping of Illumina sequence reads, Genome Research, Volume 21 (2010) no. 6, pp. 936-939 | DOI

[39] Maisonneuve, L.; Chouteau, M.; Joron, M.; Llaurens, V. Evolution and genetic architecture of disassortative mating at a locus under heterozygote advantage, Evolution, Volume 75 (2020) no. 1, pp. 149-165 | DOI

[40] Mallet, J.; McMillan, W. O.; Jiggins, C. D. Estimating the Mating Behavior of a Pair of Hybridizing Heliconius Species in the Wild, Evolution, Volume 52 (1998) no. 2 | DOI

[41] Martin, S. H.; Möst, M.; Palmer, W. J.; Salazar, C.; McMillan, W. O.; Jiggins, F. M.; Jiggins, C. D. Natural Selection and Genetic Diversity in the Butterfly Heliconius melpomene, Genetics, Volume 203 (2016) no. 1, pp. 525-541 | DOI

[42] McMillan, W. O.; Jiggins, C. D.; Mallet, J. What initiates speciation in passion-vine butterflies?, Proceedings of the National Academy of Sciences, Volume 94 (1997) no. 16, pp. 8628-8633 | DOI

[43] Mitchell-Olds, T.; Willis, J. H.; Goldstein, D. B. Which evolutionary processes influence natural genetic variation for phenotypic traits?, Nature Reviews Genetics, Volume 8 (2007) no. 11, pp. 845-856 | DOI

[44] Muers, M. Separating demography from selection, Nature Reviews Genetics, Volume 10 (2009) no. 5, pp. 280-281 | DOI

[45] Murray, G. G. R.; Soares, A. E. R.; Novak, B. J.; Schaefer, N. K.; Cahill, J. A.; Baker, A. J.; Demboski, J. R.; Doll, A.; Da Fonseca, R. R.; Fulton, T. L.; Gilbert, M. T. P.; Heintzman, P. D.; Letts, B.; McIntosh, G.; O’Connell, B. L.; Peck, M.; Pipes, M.-L.; Rice, E. S.; Santos, K. M.; Sohrweide, A. G.; Vohr, S. H.; Corbett-Detig, R. B.; Green, R. E.; Shapiro, B. Natural selection shaped the rise and fall of passenger pigeon genomic diversity, Science, Volume 358 (2017) no. 6365, pp. 951-954 | DOI

[46] Nielsen, R.; Hubisz, M. J.; Hellmann, I.; Torgerson, D.; Andrés, A. M.; Albrechtsen, A.; Gutenkunst, R.; Adams, M. D.; Cargill, M.; Boyko, A.; Indap, A.; Bustamante, C. D.; Clark, A. G. Darwinian and demographic forces affecting human protein coding genes, Genome Research, Volume 19 (2009) no. 5, pp. 838-849 | DOI

[47] Rodríguez de Cara MA angelesdecara/HnumataDemography: v1.0.0 Scripts as used in published version (v1.0.0b), Zenodo, 2023 | DOI

[48] Rodríguez de Cara, M. Á.; Jay, P.; Rougemont, Q.; Chouteau, M.; Whibley, A.; Huber, B.; Piron-Prunier, F.; Ramos, R. R.; Freitas, A. V. L.; Salazar, C.; Silva-Brandão, K. L.; Torres, T. T.; Joron, M. Balancing selection at a wing pattern locus is associated with major shifts in genome-wide patterns of diversity and gene flow, bioRxiv, 2023 (ver. 3 peer-reviewed and recommended by Peer Community in Evolutionary Biology) | DOI

[49] Rougemont Q QuentinRougemont/DemographicInference: v1.0.0 (v1.0.0)., Zenodo, 2023 | DOI

[50] Rougemont Q QuentinRougemont/slim_heliconius: slim_simulation (v1.0.0), Zenodo, 2023 | DOI

[51] Rougemont Q Balancing selection at a wing pattern locus is associated with major shifts in genome-wide patterns of diversity and gene flow (Version V1) [Data set], Zenodo, 2022 | DOI

[52] Rousset, F. Genetic Differentiation and Estimation of Gene Flow from F-Statistics Under Isolation by Distance, Genetics, Volume 145 (1997) no. 4, pp. 1219-1228 | DOI

[53] Roux, C.; Fraïsse, C.; Romiguier, J.; Anciaux, Y.; Galtier, N.; Bierne, N. Shedding Light on the Grey Zone of Speciation along a Continuum of Genomic Divergence, PLOS Biology, Volume 14 (2016) no. 12 | DOI

[54] Sánchez, A. P.; Pardo-Diaz, C.; Enciso-Romero, J.; Muñoz, A.; Jiggins, C. D.; Salazar, C.; Linares, M. An introgressed wing pattern acts as a mating cue, Evolution, Volume 69 (2015) no. 6, pp. 1619-1629 | DOI

[55] Sheppard PM; Turner JRG; Brown KS; Benson WW; Singer MC; Smith JM Genetics and the evolution of muellerian mimicry in heliconius butterflies, Philosophical Transactions of the Royal Society of London. B, Biological Sciences, Volume 308 (1985) no. 1137, pp. 433-610 | DOI

[56] Slatkin, M. Gene Flow and the Geographic Structure of Natural Populations, Science, Volume 236 (1987) no. 4803, pp. 787-792 | DOI

[57] The Heliconius Genome Consortium Butterfly genome reveals promiscuous exchange of mimicry adaptations among species, Nature, Volume 487 (2012) no. 7405, pp. 94-98 | DOI

Cited by Sources: