Transposable element polymorphisms underlie epigenetic variation and phenotypic diversification during foxtail millet domestication

Transposable elements (TEs) generate genomic variation, yet how TE polymorphisms reshape the epigenetic landscape and contribute to phenotypic diversification during domestication remains unclear. Here, we show that TE-associated genetic variants drive heritable epigenetic changes underlying key domestication traits in foxtail millet (Setaria italica), one of the oldest cereal crops domesticated in China. By analyzing DNA methylomes from 60 wild and domesticated accessions, we identify 76,815 differentially methylated regions associated with extensive polymorphic TE insertions. Epigenomic variation enables the identification of a TE inventory associated with seed shattering, branching, and growth habits. Functional analyses reveal that two DNA/PIF-Harbinger element insertions in the 5′ UTR of the pleiotropic gene SiGW3 modulate its expression and affect plant architecture, panicle morphology, and grain size. Our findings demonstrate that naturally occurring TE polymorphisms generate heritable epigenetic variation and contribute to phenotypic evolution during crop domestication, with implications for crop improvement. Foxtail millet is one of the oldest domesticated crops with climate-resilient trait and balanced nutrients. Here, the authors analyze methylome over a set of 60 foxtail millet accessions and reveal transposable element polymorphisms underlying epigenetic variation and phenotypic diversification during domestication.