Fitness-driven emergence and lineage replacement underpin the global resurgence of GII.17 noroviruses

Norovirus genotype GII.4 has dominated global gastroenteritis outbreaks for decades, limiting sustained emergence of alternative genotypes. Recent surveillance, however, shows rapid expansion of GII.17, which has overtaken GII.4 in multiple regions. Here, we reconstruct five decades of GII.17 evolution using a global genomic dataset spanning 1976–2025. We identify a single ancestral recombination event underlying the epidemic C, D and E clades, providing the genomic foundation for subsequent epidemic diversification. Contrary to expectations of pre-adaptive change, we find no evidence of intensified stem-lineage selection preceding emergence. Instead, variant E accumulated lineage-defining substitutions under relaxed selective constraints during early transmission, accompanied by shifts in mutational processes and a substantial transmission fitness advantage over prior variants. Together, these findings demonstrate that incremental post-emergence fitness gains, rather than major antigenic shifts or recurrent recombination, can enable non-dominant genotypes to overcome entrenched epidemiological barriers and drive global lineage replacement.