Understanding the forces driving species evolution is central in biology. Genetic and epigenetic variations play key roles at either short timescale, over a few hundreds of generations (micro-evolution), or over long timescale of several millions of years (macro-evolution). How the environment shapes genetic and epigenetic variations remains a central question.<br/><br/>To address this question, we investigated perennial natural populations of black poplars (Populus nigra) sampled from distinct geographic origins (France, Italy, Germany, and Netherlands) and grown in a common garden in France. We focus on cambial tissues, an important functional trait for forest trees, responsible of wood formation, in order to assess the evolutionary and functional impact of epigenetic variations at macro- (past polyploidization events) and micro- (geographical origins) scales.<br/><br/>At the macro-evolution scale, polar experienced differential structural (gene loss) and regulation (expression and methylation) reprogramming between sister genomic compartments inherited from polyploidization events. At the micro-evolution scale, both genetic and epigenetic variations differentiate populations from different geographic origins, targeting specifically genes involved in disease resistance, immune response, hormonal and stress response that can be considered as key functions of local adaptation of long lifespan species. Moreover, genes involved in cambium formation as well as in basal functions of cell development are constitutively expressed and negatively correlated with methylation level.<br/><br/>Altogether, our results highlight DNA methylation as a marker of population differentiation for long-living species and could be involved at population level with plant response to biotic and abiotic stress (R-genes, phytohormones, etc.) and at the genome level with tissue specific regulation (cambium activity, ribosome, etc.).Read less <