A flexible sterol metabolism in Capsaspora owczarzaki has features that resemble both fungi and animals

SEBASTIÁN R. NAJLE; ANTONIO D. UTTARO; IÑAKI RUIZ-TRILLO

Giens

Workshop; Spongex2015 - The Origin of Metazoans; 2015

Sterols are essential for several physiological processes in most eukaryotes, including animals. They play a key role in regulating membrane fluidity and permeability and participate in different signal transduction pathways as precursors of steroid hormones and vitamins. Sterols are also fundamental in the formation of lipid rafts, regions of reduced fluidity that selectively incorporate proteins involved in concerted functions such as cell-cell recognition, adhesion and communication. All of these cellular processes are crucial for the development and homeostasis of multicellular organisms. Sterols conform one of the most diverse fam- ilies of molecules in nature, and much of this diversity is found in non-bilaterian animals. Nevertheless, among the opisthokonts, two major types of sterols prevail. Vertebrates are characterized by having a 27-carbon (C27) sterol, namely cholesterol, as their main sterol component. On the other hand, Fungi are characterized by possessing mainly ergosterol (C28). However, information on the sterol metabolism in unicellular holozoans is scarce and so we lack a good understanding on how lipid metabolism evolved in both animals and fungi. To address this, we characterized the sterols metabolism in the filasterean Capsaspora owczarzaki, a close unicellular relative of animals. We found that the genome of C. owczarzaki encodes the complete set of genes for the canonical synthesis pathway of ergosterol, typical of Fungi, as well as an ortholog of the Rieske sterol C7(8)-desaturase, absent in Fungi and highly conserved in animals. Importantly, RNAseq data indicates a differential transcriptional regulation of this metabolism between different life stages in C. owczarzaki. This was further confirmed by using radioactive precursors and biochemical analyses. Moreover, we identified a novel sterol synthesis pathway in C. owczarzaki, which is being deployed differentially in the different life stages. Thus, in the filopodial and aggregative stages C. owczarzaki converts the cholesterol from the growth medium into ergosterol using this previously un-described synthesis pathway. On the other hand, in the cystic stage, de novo sterol synthesis leads to the production of 7-dehydrocholesterol as end product. We hypothesize that the membranes of C. owczarzaki alternate between animal-like and fungal-like sterols across its life cycle, suggesting a very versatile lipid metabolism which turns this species into a good model to study the requirements for each sterol and within the context of opisthokont evolution.