Genomic Characterization and Evolutionary Dynamics of Human Adenovirus C (HAdV-C) in Beijing (2023–2024): Insights into Multiple Recombination and Adaptive Evolution

Abstract Human adenovirus type C (HAdV-C) causes upper respiratory infections in children and may lead to severe pneumonia. During the implementation and subsequent relaxation of non-pharmaceutical interventions (NPIs), HAdV-C emerged as a transiently dominant circulating strain in Beijing. However, the fine-scale genomic architecture and the evolutionary trajectories governing its recombination remains insufficiently characterized. Between March 2023 and August 2024, respiratory samples from Beijing patients were collected and screened by qPCR. In conjunction with high-throughput whole-genome sequencing (WGS), five complete HAdV-C genomes were characterized, predominantly identified as genotypes C1 and C108, maintaining over 98% intra-typic sequence identity. Phylogenetic analysis based on whole genomic sequences revealed at least five evolutionary branches within C108. Phylogenetic reconstruction revealed a complex diversification within C108, delineating at least five distinct evolutionary clades. Specifically, the four C108 strains partitioned into two divergent sub-lineages, exhibiting close phylogenetic affinities with sequences from China and the United States. Furthermore, recombination analysis identified six discrete recombination patterns. Selection pressure analysis further demonstrated heterogenous evolutionary constraints across the genome; notably, immune-relevant early genes such as E1a_26KD exhibited elevated dN/dS ratios, harboring multiple positive selection sites. These adaptive mutations were distributed across 23 of 33 annotated genes (69.7%), suggesting extensive diversifying selection. These findings elucidate that HAdV-C evolution is synergistically driven by frequent recombination events and potent selective pressures. This study provides critical evidence for the spatiotemporal dynamics and genomic surveillance of the emerging HAdV-C variants.