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A highly diverse set of novel immunoglobulin-like transcript (NILT) genes in zebrafish indicates a wide range of functions with complex relationships to mammalian receptors

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Abstract

Multiple novel immunoglobulin-like transcripts (NILTs) have been identified from salmon, trout, and carp. NILTs typically encode activating or inhibitory transmembrane receptors with extracellular immunoglobulin (Ig) domains. Although predicted to provide immune recognition in ray-finned fish, we currently lack a definitive framework of NILT diversity, thereby limiting our predictions for their evolutionary origin and function. In order to better understand the diversity of NILTs and their possible roles in immune function, we identified five NILT loci in the Atlantic salmon (Salmo salar) genome, defined 86 NILT Ig domains within a 3-Mbp region of zebrafish (Danio rerio) chromosome 1, and described 41 NILT Ig domains as part of an alternative haplotype for this same genomic region. We then identified transcripts encoded by 43 different NILT genes which reflect an unprecedented diversity of Ig domain sequences and combinations for a family of non-recombining receptors within a single species. Zebrafish NILTs include a sole putative activating receptor but extensive inhibitory and secreted forms as well as membrane-bound forms with no known signaling motifs. These results reveal a higher level of genetic complexity, interindividual variation, and sequence diversity for NILTs than previously described, suggesting that this gene family likely plays multiple roles in host immunity.

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Data availability

New transcriptome sequence read data used in this study have been deposited to NCBI under the project accession number PRJNA672972. Custom Perl and R scripts used in the processing and formatting of data can be found on https://github.com/djwcisel/nilts.

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Acknowledgements

We thank Dereje Jima (North Carolina State University) for early discussions about zebrafish NILTs, James (Thomas) Howard (North Carolina State University) for technical support, and Shawn Burgess (National Human Genome Research Institute), John Godwin (North Carolina State University), David Langenau (Mass General Research Institute), John Rawls (Duke University), and Sergei Revskoy (University of Kentucky College of Medicine) for zebrafish lines.

Funding

This work was supported by the National Science Foundation (IOS1755330 to JAY and IOS1755242 to AD), the National Institutes of Health (R01 AI057559 to GWL and JAY and R01 AI23337 to GWL), the National Evolutionary Synthesis Center, NSF EF0905606 (DJW), the Triangle Center for Evolutionary Medicine (AD and JAY), and the Chicago Biomedical Consortium (CCT Searle Fund to JdJ and SCM), and by services provided by the University of Chicago Genomics Core Facility and Bioinformatics Core Facility which are supported by the UChicago Medicine Comprehensive Cancer Center NCI Cancer Support Center Grant (P30 CA014599).

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Authors and Affiliations

  1. Department of Molecular Biomedical Sciences, Comparative Medicine Institute, and Center for Human Health and the Environment, North Carolina State University, Raleigh, 27607, NC, USA

    Dustin J. Wcisel & Jeffrey A. Yoder

  2. Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, 28223, NC, USA

    Alex Dornburg

  3. Section of Hematology-Oncology and Stem Cell Transplant, Department of Pediatrics, The University of Chicago, Chicago, IL, USA

    Sean C. McConnell & Jill L. O. de Jong

  4. Center for Translational Data Science and Department of Medicine, University of Chicago, Chicago, IL, 60637, USA

    Kyle M. Hernandez

  5. Center for Research Informatics, University of Chicago, Chicago, IL, USA

    Jorge Andrade

  6. Current Affiliation: Kite Pharma, Santa Monica, 90404, CA, USA

    Jorge Andrade

  7. Department of Pediatrics, University of South Florida Morsani College of Medicine, St. Petersburg, 33701, FL, USA

    Gary W. Litman

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  1. Dustin J. Wcisel
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  2. Alex Dornburg
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  3. Sean C. McConnell
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  4. Kyle M. Hernandez
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  8. Jeffrey A. Yoder
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Contributions

DJW, GWL, and JAY conceived the project; DJW assembled transcriptome, datamined public databases, and wrote custom scripts to facilitate these processes; AD performed phylogenetic analyses; SCM, KMH, JA, and JdJ completed genome sequencing and assembly; DJW, AD, and JAY collected and analyzed the data, created graphics, and wrote the manuscript; JAY supervised the project. All authors read and approved the manuscript.

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Correspondence to Jeffrey A. Yoder.

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Wcisel, D.J., Dornburg, A., McConnell, S.C. et al. A highly diverse set of novel immunoglobulin-like transcript (NILT) genes in zebrafish indicates a wide range of functions with complex relationships to mammalian receptors. Immunogenetics 75, 53–69 (2023). https://doi.org/10.1007/s00251-022-01270-9

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