アイテム詳細

要旨

Animals have evolved abilities to adapt towards changes in their environments. In nematodes, the formation of long-lived, stress-resistant ‘‘dauer’’ larvae represents a key example, which is also known as major survival and dispersal strategy. Small molecules are crucial for regulation of dauer entry and have been shown to function as cues in chemical communication. Recent studies in Pristionchus pacificus and comparison to C. elegans indicated that small molecule structure and function evolve rapidly. P. pacificus contains small-molecules with building blocks from diverse primary metabolic pathways, such as ubas#1 that consists of an ascaroside to which an oxygenated, second ascaroside is attached by an ester bound. Furthermore, a 3-ureido isobutyrate moiety is attached to carbon 4 of the ascaroside resulting in a complex structure unknown from C. elegans small-molecules. However, very little is known about the enzymes and pathways involved in the synthesis of such complex small-molecules. We will highlight our approaches that aim to observe adaptations to extreme environments such as those on La Reunion Island and our attempts to associate these adaptations to molecular and biochemical functions. We report our studies on intra-species variation in small molecules production in P. pacificus on La Reunion Island. In the last 5 years, we extensively sampled a nematode population by collecting more than 300 local strains, which were subsequently characterized through a combination of genomic (RAD-sequencing) and secrotomic (HPLC/MS/MS) approaches. Per- forming genome-wide association studies (GWAS), we identified a single candidate region consisting of an operon of three esterase genes. Re-sequencing of ubas#1-deficient wild isolates indicated a deletion of one of these esterase genes. CRISPR- Cas9-induced mutation of this gene in the P. pacificus reference strain converted this strain from ubas#1-positive to ubas#1- negative strain. Thus, our study has identified an esterase involved in the synthesis of complex small-molecules. We will place our findings in the broader context of adaptations to extreme environments and will highlight the power of the P. pacificus system form integrative studies that link molecular investigations of lab-based studies to ecology, population genetics and phylogeny.