Gapless Complete Genome and Multi‐Omics Illuminate Immune Adaptation and Host‐Virus Interactions in a Coronavirus Reservoir

ABSTRACT Bats are major reservoirs of emerging viruses, including severe acute respiratory syndrome‐related coronaviruses, yet they exhibit remarkable tolerance to viral infections with limited clinical manifestations‐a longstanding immunological paradox. Here, we generate a telomere‐to‐telomere (T2T) de novo genome assembly for Rhinolophus sinicus ( R. sinicus ), designated T2T‐RSC1.0 (2.14 Gb), comprising 17 fully anchored autosomes and both sex chromosomes. This gapless assembly resolves 129.19 Mb of previously unresolved regions (PURs) and enables annotation of 848 previously unannotated genes, including 131 protein‐coding genes and five pseudogenes on the 33.75 Mb Y chromosome. Using 2.12 × 10 5 newly identified single‐nucleotide polymorphisms within PURs, population genomic analyses resolve three major genetic groups and provide improved resolution of genome‐wide population structure. Comparative analyses further reveal population‐level associations between major histocompatibility complex polymorphism and viral diversity. Multi‐omics and functional analyses reveal a coordinated evolutionary remodeling of antiviral defense, antigen presentation, cytokine signaling, and inflammatory regulation in horseshoe bats. This study provides an unparalleled genomic resource for R. sinicus and establishes an integrated framework for investigating immune evolution, long‐term host–virus coexistence, and mammalian adaptive evolution.