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dc.contributor.authorRedmond, A.K.
dc.contributor.authorMacqueen, D.J.
dc.contributor.authorDooley, H.
dc.date.accessioned2019-04-05T13:55:14Z
dc.date.available2019-04-05T13:55:14Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85056629661&doi=10.1186%2fs12862-018-1290-2&partnerID=40&md5=dd99a627ac0a077ee1cc9b532d199ac3
dc.identifier.urihttp://hdl.handle.net/10713/8839
dc.description.abstractBackground: The cartilaginous fishes diverged from other jawed vertebrates ~ 450 million years ago (mya). Despite this key evolutionary position, the only high-quality cartilaginous fish genome available is for the elephant shark (Callorhinchus milii), a chimaera whose ancestors split from the elasmobranch lineage ~ 420 mya. Initial analysis of this resource led to proposals that key components of the cartilaginous fish adaptive immune system, most notably their array of T cell subsets, was primitive compared to mammals. This proposal is at odds with the robust, antigen-specific antibody responses reported in elasmobranchs following immunization. To explore this discrepancy, we generated a multi-tissue transcriptome for small-spotted catshark (Scyliorhinus canicula), a tractable elasmobranch model for functional studies. We searched this, and other newly available sequence datasets, for CD4+ T cell subset-defining genes, aiming to confirm the presence or absence of each subset in cartilaginous fishes. Results: We generated a new transcriptome based on a normalised, multi-tissue RNA pool, aiming to maximise representation of tissue-specific and lowly expressed genes. We utilized multiple transcriptomic datasets and assembly variants in phylogenetic reconstructions to unambiguously identify several T cell subset-specific molecules in cartilaginous fishes for the first time, including interleukins, interleukin receptors, and key transcription factors. Our results reveal the inability of standard phylogenetic reconstruction approaches to capture the site-specific evolutionary processes of fast-evolving immune genes but show that site-heterogeneous mixture models can adequately do so. Conclusions: Our analyses reveal that cartilaginous fishes are capable of producing a range of CD4+ T cell subsets comparable to that of mammals. Further, that the key molecules required for the differentiation and functioning of these subsets existed in the jawed vertebrate ancestor. Additionally, we highlight the importance of considering phylogenetic diversity and, where possible, utilizing multiple datasets for individual species, to accurately infer gene presence or absence at higher taxonomic levels. © 2018 The Author(s).en_US
dc.description.sponsorshipWe are grateful to Dr. Elaina Collie-Duguid, Prof David Salt (University of Nottingham), Mr. Brennan Martin, Mrs. Diane Stewart, and the rest of the Centre for Genome-Enabled Biology and Medicine team at University of Aberdeen for their advice and/or technical assistance. We thank Dr. Abdullah Alzaid for advice on RNA isolation, and Dr. Rita Pettinello for assistance with tissue sampling (both University of Aberdeen). We acknowledge the support of the Maxwell compute cluster funded by the University of Aberdeen. Finally, we extend thanks to Dr. Tom Williams (University of Bristol) for helpful discussion, and Dr. Bui Quang Minh (Centre for Integrative Bioinformatics Vienna) for advice on IQ-tree model implementation.en_US
dc.description.urihttps://dx.doi.org/10.1186/s12862-018-1290-2en_US
dc.language.isoEnglishen_US
dc.publisherBioMed Central Ltd.en_US
dc.relation.ispartofBMC Evolutionary Biology
dc.subjectCartilaginous fishen_US
dc.subjectElasmobranchen_US
dc.subjectImmune gene evolutionen_US
dc.subjectImmunityen_US
dc.subjectInterleukinen_US
dc.subjectPhylogenetic rootingen_US
dc.subjectSharken_US
dc.subjectSite-heterogeneous modelsen_US
dc.subjectT cellen_US
dc.subjectTranscriptomeen_US
dc.titlePhylotranscriptomics suggests the jawed vertebrate ancestor could generate diverse helper and regulatory T cell subsetsen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s12862-018-1290-2
dc.identifier.pmid30442091


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