Daphnia and Drosophila: two invertebrate models for O 2 responsive and HIF-mediated regulation of genes and genomes

Abstract

A brief comparison of hypoxia-tolerant versus hypoxia-sensitive strategies to cope with periods of oxygen deprivation (hypoxia, anoxia) is presented with a particular focus on oxygen sensing via hypoxia-inducible factors (HIF) in two hypoxia-tolerant invertebrate models: Daphnia magna and Drosophila melanogaster. In Daphnia, HIF controls the hypoxic induction of multiple globin genes, which, not only causes a visible development of color, but also greatly facilitates O 2 delivery to hypoxic tissues as do HIF-driven erythropoiesis and angiogenesis in mammals. In contrast, expression of the single-copy drosophilid globin gene is HIF-dependently suppressed in hypoxic SL2 cells from late fly embryos. Invertebrate globin genes, therefore, demonstrate HIF's ability to confer trans-activation and trans-inactivation onto target genes. Strategies to acquire hypoxia-tolerance center around a regulated and reversible metabolic depression throughout which cellular ATP supply and demand functions are coordinatedly reduced. Our microarray-based elucidation of Drosophila's genome-wide response to graded hypoxia revealed indeed numerous transcriptional inductions or suppressions that suggested an overall down-regulation of major ATP consuming processes (e.g. protein synthesis, cell cycle progression) in severely oxygen depleted SL2 cells. HIF control was implicated in some of these regulations and thus, might play an essential role to conserve energy during periods of limited O 2 supply in hypoxia-tolerant animals.