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By integrating population-level sampling, we show that apparent population-specific structural and regulatory variation inferred from single-reference genomes is overestimated, reflecting pervasive reference bias. While structural variants contribute to genomic variation, in our system, most are shared or polymorphic rather than fixed differences between populations. Together, our results show that the genomic landscape of\n                    <jats:italic toggle=\"yes\">H. erato<\/jats:italic>\n                    divergence reflects the combined contributions of regulatory variation and mutational change, while highlighting the importance of accounting for reference bias when interpreting structural and regulatory divergence. This multilocus framework provides a more accurate view of how reproductive barriers emerge and strengthen under ongoing gene flow.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz6665","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:58:41Z","timestamp":1787335121000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Multilocus basis of incipient reproductive isolation in hybridizing populations is revealed by pangenomic and epigenetic divergence"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1427-2667","authenticated-orcid":true,"given":"Angelo A.","family":"Ruggieri","sequence":"first","affiliation":[{"name":"Department of Biology, University of Puerto Rico, Rio Piedras, Puerto Rico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cicconardi","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Bristol University, Bristol, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7451-5398","authenticated-orcid":true,"given":"Nicol\u00f2","family":"Bellin","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico, Rio Piedras, Puerto Rico."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5474-5695","authenticated-orcid":true,"given":"Stephen H.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Bristol University, Bristol, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3370-0367","authenticated-orcid":true,"given":"James","family":"Mallet","sequence":"additional","affiliation":[{"name":"Organismal and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-1007","authenticated-orcid":true,"given":"Steven M.","family":"Van Belleghem","sequence":"additional","affiliation":[{"name":"Ecology, Evolution, and Conservation Biology, Biology Department, KU Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2805-2745","authenticated-orcid":true,"given":"Owen W.","family":"McMillan","sequence":"additional","affiliation":[{"name":"Smithsonian Tropical Research Institute, Panama, Panama."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2724-071X","authenticated-orcid":true,"given":"Brian A.","family":"Counterman","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-9993","authenticated-orcid":true,"given":"Riccardo","family":"Papa","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico, Rio Piedras, Puerto Rico."},{"name":"Molecular Sciences and Research Center, University of Puerto Rico, San Juan, Puerto Rico."},{"name":"Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico."},{"name":"Dipartimento di Scienze chimiche della vita e della Sostenibilit\u00e0 Ambientale, Universit\u00e0 di Parma, Parma 43124, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-7-28"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1420-9101.2012.02599.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1420-9101.2001.00335.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2011.0263"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2011.0260"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004966"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2017.0335"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/evo.14272"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes12071084"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142727.mb2129s109"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/341497a0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88349-7"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2006288"},{"key":"e_1_3_2_15_2","first-page":"104","article-title":"Interactive maps for visualizing geographic distributions and phenotypes","volume":"34","author":"Rosser N.","year":"2024","unstructured":"N. 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