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

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Název: Exploitation of phylum-spanning omics resources reveals complexity in the nematode FLP signalling system and provides insights intoflp-gene evolution
Autoři: Mccoy, Ciaran J., Wray, Christopher P., Freeman, Laura, Crooks, Bethany A., Golinelli, Luca, Marks, Nikki J., Temmerman, Liesbet, Beets, Isabel, Atkinson, Louise E., Mousley, Angela
Zdroj: BMC Genomics
BMC Genomics, Vol 25, Iss 1, Pp 1-17 (2024)
McCoy, C J, Wray, C P, Freeman, L, Crooks, B A, Golinelli, L, Marks, N J, Temmerman, L, Beets, I, Atkinson, L E & Mousley, A 2024, 'Exploitation of phylum-spanning omics resources reveals complexity in the nematode FLP signalling system and provides insights into flp-gene evolution', BMC Genomics, vol. 25, 1220 . https://doi.org/10.1186/s12864-024-11111-6
Informace o vydavateli: Cold Spring Harbor Laboratory, 2024.
Rok vydání: 2024
Témata: 0301 basic medicine, genomics/methods, Nematoda, Bioinformatics, FLP, DIVERSITY, QH426-470, phylogeny, Evolution, Molecular, 03 medical and health sciences, evolution, Genetics, Animals, neuropeptides/genetics, molecular, name=SDG 3 - Good Health and Well-being, Pan-phylum, PARASITE, Nematode parasite, 11 Medical and Health Sciences, Phylogeny, Genetics & Heredity, 0303 health sciences, Science & Technology, Genome, 31 Biological sciences, Research, Neuropeptides, evolution, molecular, nematoda/genetics, 32 Biomedical and clinical sciences, Genomics, 06 Biological Sciences, animals, Biotechnology & Applied Microbiology, FMRFamide-like peptide, 08 Information and Computing Sciences, Transcriptome, Life Sciences & Biomedicine, signal transduction, NEUROPEPTIDE, TP248.13-248.65, Biotechnology, Signal Transduction
Popis: 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 2143flp-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-spanningflps, flp-1, −8, −14, and −18, may be representative of theflpprofile of the last common ancestor of nematodes; (ii) the majority of parasitic nematodes have a reducedflpcomplement relative to free-living species; (iii) FLP prepropeptide architecture is variable within and betweenflp-genes and across nematode species; (iv) FLP prepropeptide signatures facilitateflp-gene discrimination; (v) FLP motifs display variable length, amino acid sequence, and conservation; (vi) CLANS analysis provides insight into the evolutionary history offlp-gene sequelogues and reveals putativeflp-gene paralogues and, (viii)flpexpression 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.
Druh dokumentu: Article
Other literature type
Popis souboru: application/pdf
ISSN: 1471-2164
DOI: 10.1101/2024.08.25.609560
DOI: 10.1186/s12864-024-11111-6
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39702046
https://doaj.org/article/af4400146b174d1fb314bad0ad52d675
https://pure.qub.ac.uk/en/publications/d9c1e5bb-211b-4157-950e-351801656636
Rights: CC BY
URL: https://www.biorxiv.org/about/FAQ#license
Přístupové číslo: edsair.doi.dedup.....50b596735fd2d2e5a6ac7f801fa97c97
Databáze: OpenAIRE
Popis
Abstrakt: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 2143flp-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-spanningflps, flp-1, −8, −14, and −18, may be representative of theflpprofile of the last common ancestor of nematodes; (ii) the majority of parasitic nematodes have a reducedflpcomplement relative to free-living species; (iii) FLP prepropeptide architecture is variable within and betweenflp-genes and across nematode species; (iv) FLP prepropeptide signatures facilitateflp-gene discrimination; (v) FLP motifs display variable length, amino acid sequence, and conservation; (vi) CLANS analysis provides insight into the evolutionary history offlp-gene sequelogues and reveals putativeflp-gene paralogues and, (viii)flpexpression 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.
ISSN:14712164
DOI:10.1101/2024.08.25.609560