Ogura, K. | Search bioRxiv

bioRxiv2026

Profiling cell proliferation after whole-genome duplication in human cells

Though whole-genome duplication (WGD) contributes to cancer progression, the mechanism of post-WGD cell proliferation remains unclear. Here, using 6-day live-imaging, we analyzed the proliferation dynamics of more than 150 post-WGD HCT116 cell lineages. A quantitative comparison of mitotic patterns and cell fates between proliferative and non-proliferative lineages revealed that multipolar chromosome segregation in early mitosis is a key factor limiting the proliferative capacity of post-WGD progenies. Multipolar chromosome segregation suppressed post-WGD cell viability, particularly when accompanied by drastic chromosome loss or when it repeatedly occurred. Tracing proliferative lineages elucidated that they proliferated mainly by imposing the risk of multipolar chromosome segregation on one of two sub-lineages that formed after the first bipolar division. Meanwhile, a considerable proportion of proliferative lineages consisted entirely of progeny of early multipolar chromosome segregation events. Our results highlight key cellular events that determine the proliferation dynamics and diversity of post-WGD progenies, providing a fundamental reference for understanding WGD-associated bioprocesses. Summary statementLive image tracing of >150 cell lineages reveals the cross-generation dynamics of multipolar chromosome segregation that determine the fates of post-whole-genome duplication progeny cells.

cell biology↗

bioRxiv2025

Molecular evolution and diversity of isomerase-reductase operons involved in bacterial metabolism of glycosaminoglycans

Glycosaminoglycans (GAGs), comprising uronic acids and amino sugars, are widely distributed in human tissues such as the intestine and oral cavity. Various bacteria colonize these tissues by assimilating GAGs. 4-Deoxy-L-threo-5-hexosulose uronate (DHU) is produced during the degradation of GAGs. Pectin, abundant in plants, is also degraded into DHU. DHU is metabolized in a stepwise manner by the isomerase KduI or DhuI, followed by the reductase KduD or DhuD. Previous studies have shown that the two genes encoding isomerase and reductase (kduI-kduD and dhuD-dhuI, respectively) are designated in an operon. Therefore, it was believed that dhuD-dhuI and kduI-kduD operons evolved independently. Nevertheless, the discovery of a hybrid kduI-dhuD operon raised questions regarding the evolution of these operons. This study was conducted to investigate the factors driving the diversity of operons through a pan-genomic phylogenetic analysis across 3550 bacterial strains. Seven types of DHU metabolism-related operons were identified. The phylum Bacteroidota possesses a hybrid-type kduI-dhuD operon rather than kduI-kduD or kduD-kduI operon. The phylum Bacillota, but not Pseudomonadota or Bacteroidota, possesses the dhuD-dhuI operon; however, dhuI-dhuD operon was not detected in any bacterial strain. Although DHU is generated from the degradation of oligomerized GAG by an unsaturated glucuronyl hydrolase (UGL), the UGL gene was found in strains positive for kduD-kduI, dhuD-dhuI, kduI-dhuD, and dhuD-kduI operons at high ratios, indicating that the acquisition of these operons is advantageous for colonization on human hosts. (230 words) IMPORTANCEGlycosaminoglycans (GAGs), crucial components of the extracellular matrix, play a vital role in host infection by pathogenic bacteria as well as in the colonization of the host by commensal bacteria. The isomerases KduI and DhuI are nonhomologous isofunctional enzymes. The dhuD-dhuI operon is well conserved within certain phyla and appears to have a strong association with GAG metabolism. In contrast, the kduI system is more widely distributed across various species. Based on the possession ratios of genes encoding each enzyme that produces 4-deoxy-L-threo-5-hexosulose uronate, this study indicated that the substrates targeted by each metabolic system vary depending on the specific operon type.

microbiology↗