Global characterization of Dictyostelium discoideum gene expression changes under hypoxic conditions

Aerobic eukaryotes utilize O ₂ to oxidize metabolites and generate ATP. The protist kingdom lacks the Hypoxia Inducible Factor-dependent transcriptional response network to accommodate low O ₂ though possesses a HIF prolyl hydroxylase that initially mediates the response. To address the scale and scope of hypoxic responses in protists, we characterized transcriptomic and proteomic changes when the social amoeba Dictyostelium is subjected to low (1%) O ₂ under nutritive conditions over 24 h followed by reoxygenation. Remarkably, 32% of the transcripts quantified were differentially expressed during hypoxia, with greatest changes associated with early (1 h) and late phases (24 h). Protein changes were modestly correlated with and generally lagged behind transcriptional changes. Correlated changes were observed for transcripts and proteins associated with various metabolic, anabolic, and catabolic pathways, as well as chromosome organization, cell cycling, vesicular trafficking, and signaling. Analysis of 4 marker genes showed extremely rapid responses that were graded over a range of O ₂ levels, with differential responses to inhibitors affecting protein synthesis and mitochondria. Overall, the amoebal response to a low but non-toxic O ₂ -level resulted in massive remodeling of the transcriptome and proteome.