The dual role of whole-genome duplication: biological mechanisms, functional consequences, and detection advances

Whole-genome duplication (WGD) represents an evolutionarily conserved process occurring in prokaryotes, eukaryotes, and somatic mammalian tissues. While developmentally programmed WGD supports normal tissue regeneration, unscheduled WGD drives chromosomal instability and oncogenic progression in cancer. Recent studies have clarified dual roles of WGD across physiological homeostasis and disease pathogenesis. Here, we review the prevalence of WGD, the molecular mechanisms driving its major causes and its biological consequences. In addition, we highlight recent advancements in WGD detection, including both conventional cytogenetic techniques and newly developed high-throughput sequencing approaches. The integration of multi-omics and machine learning further improves ploidy analysis, particularly in cancer research. Together, these insights establish WGD as a critical regulator of development, regeneration, and disease and underscore the importance of emerging computational and sequencing tools for its precise characterization.