The interplay between prior selection, mild intermittent exposure, and acute severe exposure in phenotypic and transcriptional response to hypoxia

Abstract

Hypoxia has profound and diverse effects on aerobic organisms, disrupting oxidative phosphorylation and activating several protective pathways. Predictions have been made that exposure to mild intermittent hypoxia may be protective against more severe exposure and may extend lifespan. Here we report the lifespan effects of chronic, mild, intermittent hypoxia, and short‐term survival in acute severe hypoxia in four clones of Daphnia magna originating from either permanent or intermittent habitats. We test the hypothesis that acclimation to chronic mild intermittent hypoxia can extend lifespan through activation of antioxidant and stress‐tolerance pathways and increase survival in acute severe hypoxia through activation of oxygen transport and storage proteins and adjustment to carbohydrate metabolism. Unexpectedly, we show that chronic hypoxia extended the lifespan in the two clones originating from intermittent habitats but had the opposite effect in the two clones from permanent habitats, which also showed lower tolerance to acute hypoxia. Exposure to chronic hypoxia did not protect against acute hypoxia; to the contrary, Daphnia from the chronic hypoxia treatment had lower acute hypoxia tolerance than normoxic controls. Few transcripts changed their abundance in response to the chronic hypoxia treatment in any of the clones. After 12 h of acute hypoxia treatment, the transcriptional response was more pronounced, with numerous protein‐coding genes with functionality in oxygen transport, mitochondrial and respiratory metabolism, and gluconeogenesis, showing upregulation. While clones from intermittent habitats showed somewhat stronger differential expression in response to acute hypoxia than those from permanent habitats, contrary to predictions, there were no significant hypoxia‐by‐habitat of origin or chronic‐by‐acute treatment interactions. GO enrichment analysis revealed a possible hypoxia tolerance role by accelerating the molting cycle and regulating neuron survival through upregulation of cuticular proteins and neurotrophins, respectively.

Differential Expression of Gluconeogenesis-Related Transcripts in a Freshwater Zooplankton Model Organism Suggests a Role of the Cori Cycle in Hypoxia Tolerance

“…We selected this clone from a panel of four as it was the one characterized by the lowest pyruvate accumulation in tissues, hypothetically indicating the utilization of pyruvate for lactic fermentation and/or GNG. This clone has previously been demonstrated to be the most hypoxia-tolerant of the four clones tested [18]. We observed a significant upregulation of PEPCK-C and FBP (but not of PC) in hypoxia in both body parts when normalized by a reference gene unrelated to carbohydrate metabolism (Fig.…”

“…Hereafter, we refer to these clones by the first two letters of their Basel stock IDs. Previous longevity studies indicate that these clones differ significantly in their lifespan and acute hypoxia tolerance, with FI and IL being the short-lived, hypoxia-tolerant clones, and GB and HU showing higher longevity but lower hypoxia tolerance [18]. Stocks were maintained in modified ADaM zooplankton medium (Ref.…”

“…Typically, no mortality occurs in 12 hours at 1 mg O 2 /L, with survival times ranging between 17 and 30 hours [18]. This experiment was conducted in two randomized blocks on two different dates, with 48 and 16…”

“…We have previously analyzed differential gene expression in response to mild chronic and severe acute hypoxia in a classic model organism for aquatic ecophysiology, Daphnia magna [18] revealing that while only a small subset of abundant transcripts showed differential expression responses under mild chronic hypoxic conditions, many, including the GNG-specific PEPCK-C, showed upregulation in acute severe hypoxia. Aralar1, a mitochondrial carrier protein that transports aspartate from the mitochondria to the cytosol, also showed upregulation in hypoxia.…”

Short lifespan is one’s fate, long lifespan is one’s achievement: lessons fromDaphnia

“…The disadvantage of this approach, as any other similar meta-analysis, is that it is not, for most types of comparisons, a common garden analysis. Most of the experiments analyzed were designed to test various hypotheses about aging and longevity, such as about effects of maternal age (Anderson et al 2022b), hypoxia (Ekwudo et al 2022), or biochemical interventions (Pearson and Yampolsky in preparation), or simply to obtain Daphnia of different ages for a variety of aging hallmark assays (Anderson et al 2022a;Lowman and Yampolsky 2023). Hence variation in experimental protocols, in addition to any uncontrolled differences among experiments which may range from quality of algal food to details of maternal treatment or skills of individual investigators.…”