Hosoya, K. | Search bioRxiv

bioRxiv2025

Century-old ethanol-preserved Vega Collection reveal the unexpected phylogeography of Slender bitterling Tanakia lanceolata in Japan

Recent genetic advancements offer new opportunities for studying natural history museum collections. The genetic analysis of century-old aquatic animal specimens, mostly preserved in ethanol, can provide valuable insights into the changes in genetic diversity caused by anthropogenic impacts. However, knowledge of the characteristics of degraded DNA from such specimens remains limited. In this study, we evaluated the DNA quality of bitterling fish, Tanakia lanceolata (Temminck and Schlegel), collected during the Vega Expedition in Japan in 1879 and preserved in ethanol. We then performed genomic analysis to test its hypothesized translocation-involved population history. The historical DNA was degraded, peaking around 50 bp, but a minor fraction exceeded 300 bp. Mitochondrial genetic analysis revealed high genetic similarity between the eastern and western sides of the Central Highland, typically impeding the dispersal of primary freshwater fish. These findings suggest an unexpected dispersal ability in T. lanceolata or undocumented translocations before the large-scale domestic translocations recorded since the 1910s. The customized workflow for historical ethanol-preserved specimens, based on historical DNA quality in this study, provides a foundation for studying historical archives.

evolutionary biology↗

bioRxiv2025

Lysine lactylation regulates ATF4-mediated stress responses under glucose starvation in canine hemangiosarcoma

Hemangiosarcoma (HSA) is a malignant endothelial tumor that occurs frequently in dogs but is rare in other species including humans. Due to its aggressive behavior and limited therapeutic options, patient prognosis is generally poor. Tumor cells produce excess lactate via anerobic glycolysis, and it regulate gene expressions through histone lactylation in response to cellular metabolic conditions. However, how histone lactylation affects biological behavior under glucose-limited conditions in HSA remains unknown. Here, we established canine HSA cell lines and patient-derived xenograft models and investigated the role of histone lactylation during glucose deprivation. HSA cells exhibited higher global histone lactylation levels than normal endothelial cells. Although glucose restriction reduced global histone lactylation levels, Cleavage Under Targets and Tagmentation (CUT&Tag) analysis revealed enrichment of lactylation peaks at transcription-start sites (TSSs) of ATF4-regulated stress-response, asparagine biosynthesis and immune-related genes. TSSs of stress-response genes were co-occupied with RNA polymerase II phosphorylated at serine 5 and showed increased gene expressions, suggesting that lactylation at TSSs activated transcription under glucose-deprived conditions. [U-13C]glutamine tracing indicated that HSA cells synthesized asparagine from glutamine when glucose was scarce. Asparagine supplementation modestly activated cell proliferation. In HSA patient tissues, H3K18la levels were heterogeneous, and M2-like macrophages preferentially infiltrated tumor regions showing low histone lactylation levels. Consistently, glucose-starved HSA cells attracted macrophages and induced M2-like polarization in vitro. These findings demonstrate that lysine lactylation, possibly histone lactylation, persists even under glucose-deprived conditions and regulate transcription that supports tumor cell survival and fosters a pro-tumor microenvironment. One Sentence SummaryLysine lactylation is enriched at TSSs of stress-response genes under glucose starvation and associated with their transcription in canine hemangiosarcoma.

cancer biology↗