Exploitation of phylum-spanning omics resources reveals complexity in the nematode FLP signalling system and provides insights into flp-gene evolution

McCoy, C. J.; Wray, C.; Freeman, L.; Crooks, B. A.; Golinelli, L.; Marks, N. J.; Temmerman, L.; Beets, I.; Atkinson, L. E.; Mousley, A.

doi:10.1101/2024.08.25.609560

bioRxiv · 10.1101/2024.08.25.609560

Exploitation of phylum-spanning omics resources reveals complexity in the nematode FLP signalling system and provides insights into flp-gene evolution

McCoy, C. J.·Wray, C.·Freeman, L.·Crooks, B. A.·Golinelli, L.·Marks, N. J.·Temmerman, L.·Beets, I.·Atkinson, L. E.·Mousley, A.

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Abstract

BackgroundParasitic nematodes significantly undermine global human and animal health and productivity. Parasite control is reliant on anthelmintic administration however over-use of a limited number of drugs has resulted in escalating parasitic nematode resistance, threatening the sustainability of parasite control and underscoring an urgent need for the development of novel therapeutics. FMRFamide-like peptides (FLPs), the largest family of nematode neuropeptides, modulate nematode behaviours including those important for parasite survival, highlighting FLP receptors (FLP-GPCRs) as appealing putative novel anthelmintic targets. Advances in omics resources have enabled the identification of FLPs and neuropeptide-GPCRs in some parasitic nematodes, but remaining gaps in FLP-ligand libraries hinder the characterisation of receptor-ligand interactions, which are required to drive the development of novel control approaches. ResultsIn this study we exploited recent expansions in nematode genome data to identify 2143 flp-genes in >100 nematode species across free-living, entomopathogenic, plant, animal and human lifestyles and representing 7 of the 12 major nematode clades (1). Our data reveal that: (i) the phylum-spanning flps, flp-1, -8, -14, and -18, may be representative of the flp profile of the last common ancestor of nematodes; (ii) the majority of parasitic nematodes have a reduced flp complement relative to free-living species; (iii) FLP prepropeptide architecture is variable within and between flp-genes and across nematode species; (iv) FLP prepropeptide signatures facilitate flp-gene discrimination; (v) FLP motifs display variable length, amino acid sequence, and conservation; (vi) CLANS analysis provides insight into the evolutionary history of flp-gene sequelogues and reveals putative flp-gene paralogues and, (viii) flp expression is upregulated in the infective larval stage of several nematode parasites. ConclusionsThese data provide the foundation required for phylum-spanning FLP-GPCR deorphanisation screens in nematodes to seed the discovery and development of novel parasite control approaches.

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McCoy, C. J., Wray, C., Freeman, L., Crooks, B. A., Golinelli, L., Marks, N. J., Temmerman, L., Beets, I., Atkinson, L. E., Mousley, A.. 2024-08-26. Exploitation of phylum-spanning omics resources reveals complexity in the nematode FLP signalling system and provides insights into flp-gene evolution. https://doi.org/10.1101/2024.08.25.609560

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