Polygenic basis of incipient reproductive isolation in hybridizing populations is revealed by pangenomic and epigenetic divergence

Abstract

Incipient reproductive isolation in the presence of gene flow has traditionally been attributed to a small number of major-effect loci under strong selection, representing only a minor fraction of the genome. Using the Heliconius erato adaptive radiation--a butterfly species with populations at varying levels of genetic differentiation--we employed a pan-genome approach to investigate genome-wide mutational divergence, epigenetic changes, and structural variation contributing to divergence. In contrast to earlier studies that identified only a few highly divergent loci, our high-resolution analysis reveals widespread divergence across the genome, suggesting polygenic barriers to gene flow. Epigenetic divergence assessed using ATAC-seq, highlights population-specific differences in chromatin accessibility, which may reflect SNPs distribution or precede genetic differentiation by reshaping regulatory landscapes. We also identified new structural variants, including polymorphic indels in open chromatin, that further associate with genomic divergence. Together, these findings show that the genomic landscape of H. erato is shaped by a dynamic interplay of mutational changes, epigenetic modifications, and structural variation. We emphasize the role of developmental, behavioral, and ecological adaptations and provide a broader perspective on the functional genetic basis of genome-wide divergence in Heliconius. This emerging polygenic framework offers a more detailed understanding of how reproductive barriers evolve under ongoing gene flow.