The role of sirtuins in mediating the hypoxic response in Danio spp.

It is widely believed that hypoxia-tolerant species have evolved specialized strategies to survive in low-oxygen environments, but the exact mechanisms behind these adaptations are still not fully understood. This thesis investigates mechanisms underlying interspecific variation in hypoxia tolerance among Danio species, focusing on mitochondrial sirtuin proteins (SIRT3, SIRT4, SIRT5) and metabolic responses. Phylogenetic analysis of sirtuin sequences from diverse fish species revealed grouping by family, emphasizing evolutionary conservation. Among species with varying hypoxia tolerance, as indicated by differences in Pcrit, in silico analysis of sirtuin isoelectric point, hydropathicity, and stability found no relationships between Pcrit and these protein properties. To investigate physiological responses to hypoxia, zebrafish (Danio rerio), pearl danio (Danio albolineatus), and glowlight danio (Danio choprai) were exposed to a variety of oxygen tensions scaled to the species-specific 8-hour EC50 values. Zebrafish, the most hypoxia-tolerant species, exhibited lower lactate accumulation than the other species, indicating reduced reliance on anaerobic metabolism and possibly greater aerobic efficiency. Gene expression analysis of sirt3 revealed significant species differences under normoxia, with higher expression in pearl danio compared to zebrafish in the gills, suggesting a potential role for sirt3 in shaping baseline physiological differences that could impact hypoxia responses. This comparative analysis highlights that while hypoxia tolerance is linked to some metabolic traits and evolutionary patterns, these connections were inconsistent. Other mechanisms beyond SIRT likely contribute to explaining the interspecific variation in hypoxia tolerance among Danio spp, emphasizing the complexity of adaptation to low-oxygen environments.