Carrier, A. | Search bioRxiv

bioRxiv2018

Combining population genomics and forward simulations to investigate stocking impacts: A case study of Muskellunge (Esox masquinongy) from the St. Lawrence River basin

Understanding the genetic and evolutionary impacts of fish stocking on wild populations has long been of interest as negative consequences such as reduced fitness and loss of genetic resources are commonly reported. Nearly five decades of extensive stocking of over a million Muskellunge (Esox masquinongy) in the Lower St. Lawrence River (Quebec, Canada) was implemented by managers in an attempt to sustain a fishery. We investigated the effect of stocking on this native species genetic structure and allelic diversity in the St. Lawrence river and its tributaries as well as several stocked inland lakes. Using Genotype-By-Sequencing (GBS), we genotyped 643 individuals representing 22 sampling sites and combined this information with forward simulations to investigate the genetic consequences of stocking. Individuals native to the St. Lawrence watershed were genetically divergent from the sources used for stocking and both the St. Lawrence tributaries and inland lakes were also naturally divergent from the main stem. Empirical data and simulations revealed weak effects of stocking on admixture patterns within the St. Lawrence despite intense stocking in the past, whereas footprints of admixture were higher in the smaller stocked populations from tributaries and lakes. Altogether, our data suggests that selection against introgression has been relatively efficient within the large St. Lawrence River. In contrast, the smaller populations from adjacent tributaries and lakes still displayed stocking related admixture which apparently resulted in higher genetic diversity, suggesting that, while stocking stopped at the same time, its impact remained higher in these populations. Finally, the origin of populations from inland lakes that were established by stocking confirmed their close affinity with these source populations. This study illustrates the benefit of combining extensive genomic data with forward simulations for improved inferences regarding outcomes of population enhancement by stocking, as well as its relevance for fishery management decision making.

evolutionary biology↗

bioRxiv2018

Inactivation of NUPR1 promotes cell death by coupling ER-stress responses with necrosis

Genetic inhibition of NUPR1 induces tumor growth arrest. Inactivation of NUPR1 expression in pancreatic cancer cells results in lower ATP production, higher consumption of glucose with a significant switch from OXPHOS to glycolysis followed by necrotic cell death. Importantly, induction of necrosis is independent of the caspase activity. We demonstrated that NUPR1 inactivation triggers a massive release of Ca2+ from the endoplasmic reticulum (ER) to the cytosol and a strong increase in ROS production by mitochondria with a concomitant relocalization of mitochondria to the vicinity of the ER. In addition, transcriptomic analysis of NUPR1-deficient cells shows the induction of an ER stress which is associated to a decrease in the expression of some ER stress response-associated genes. Indeed, during ER stress induced by the treatment with thapsigargin, brefeldin A or tunicamycin, an increase in the mitochondrial malfunction with higher induction of necrosis was observed in NUPR1-defficent cells. Finally, activation of NUPR1 during acute pancreatitis protects acinar cells of necrosis in mice. Altogether, these data enable us to describe a model in which inactivation of NUPR1 in pancreatic cancer cells results in an ER stress that induces a mitochondrial malfunction, a deficient ATP production and, as consequence, the cell death by necrosis.\n\nHighlightsNUPR1 expression promotes pancreatic cancer development and progression\n\nNUPR1-depletion is a promising therapeutic strategy to be used for treating cancers\n\nNUPR1-depletion induces ER stress, mitochondrial malfunction and a significant switch from OXPHOS to glycolysis followed by necrotic cell death\n\nInactivation of NUPR1 antagonizes cell growth by coupling a defective ER-stress response and a caspase-independent necrosis.

cell biology↗