Genome analysis reveals unexpected absence of oxygen metabolic capacity in helminths

Abstract

Oxygen metabolism in parasitic helminths differs significantly from that of most aerobic eukaryotes, as these organisms must be able to switch between aerobic and anaerobic metabolisms depending on their life-cycle stage. These parasites also require robust antioxidant defense systems that allow them to survive bursts of reactive oxygen species (ROS) released by their hosts. Early metabolism studies suggested a lack of cytochrome c oxidase (COX) activity in certain parasitic helminths, and the role of COX in helminth mitochondria remains unclear. To determine whether a functional COX is widely present in helminths, we analyzed the phylogenetic distribution of oxygen metabolism systems across 129 helminth genomes, investigating three distinct sets of protein-coding genes involved in different aspects of oxygen metabolism: COX and its assembly factors, peroxisomal genes, and genes coding for the most abundant ROS-metabolizing proteins. While glycolytic and citric acid cycle enzymes are highly conserved in helminthic species, in tracking the presence of genes associated with the electron transport chain we observed that certain lineages of parasitic worm have lost genes associated with COX and its assembly factors. Although most common genes encoding proteins involved in the defense against ROS are maintained across virtually all lineages, many species exhibit complete absence of peroxisomal metabolic pathways, including an absence of catalase. Our results suggest that a subset of parasitic nematodes and platyhelminths utilize oxygen differently from related, non-parasitic worms such as C. elegans, with significant differences in their mitochondrial electron transport chains and peroxisomes. The identification of substantive metabolic differences between the parasitic helminths and their mammalian hosts offers a new avenue for the development of anthelminthic therapeutics.