Pangenome reveals large‐scale gene loss as a key strategy for adaptive evolution in Agaricus bisporus

Abstract Gene loss is a widespread phenomenon in species evolution, yet the evolutionary significance of large‐scale gene loss—whether arising through neutral processes or adaptive evolution—remains a subject of ongoing debate. Agaricus bisporus , a globally distributed macrofungus, serves as an ideal model to investigate this phenomenon. Utilizing the “map‐to‐pan” method, we constructed a high‐resolution pangenome comprising 30 793 genes and 143 Mb of additional sequences, including 21 370 genes absent in the reference genome. Phylogenetic and admixture analyses identified four genetic lineages: the globally distributed MIX and region‐specific European, America, and Highland lineages. Core gene analyses revealed a substantially lower genetic load in MIX lineage, accompanied by a marked reduction in the frequency of deleterious mutations compared with other lineages. Presence–absence variation (PAV) analyses further demonstrated extensive gene loss in MIX lineage, with functional enrichment analyses associating these PAVs with DNA damage repair pathways. This finding suggests that gene loss could enhance tolerance to DNA damage, thereby mitigating mutation accumulation. A significantly higher proportion of lost PAVs in MIX lineage was under selective pressure, supporting gene loss as an adaptive strategy. Our findings highlight two key mechanisms facilitating the MIX lineage's broad distribution: (1) the reduction of deleterious mutations, thereby lowering genetic load, and (2) the selective loss of redundant, non‐essential genes, enhancing adaptability across diverse environments. This study not only underscores the adaptive significance of large‐scale gene loss in the evolution of A. bisporus but also offers a broader framework for understanding how gene loss events shape the evolutionary trajectories of other fungal species.