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Home / Equine Research Bank / BMC Evol Biol / Alternative splicing after gene duplication drives CEACAM1-p...
BMC evolutionary biology2018; 18(1); 32; doi: 10.1186/s12862-018-1145-x

Alternative splicing after gene duplication drives CEACAM1-paralog diversification in the horse.

Abstract: The CEA gene family is one of the most rapidly evolving gene families in the human genome. The founder gene of the family is thought to be an ancestor of the inhibitory immune checkpoint molecule CEACAM1. Comprehensive analyses of mammalian genomes showed that the CEA gene family is subject to tremendous gene family expansion and contraction events in different mammalian species. While in some species (e.g. rabbits) less than three CEACAM1 related genes exist, were in others (certain microbat species) up to 100 CEACAM1 paralogs identified. We have recently reported that the horse has also an extended CEA gene family. Since mechanisms of gene family expansion and diversification are not well understood we aimed to analyze the equine CEA gene family in detail. We found that the equine CEA gene family contains 17 functional CEACAM1-related genes. Nine of them were secreted molecules and eight CEACAMs contain transmembrane and cytoplasmic domain exons, the latter being in the focus of the present report. Only one (CEACAM41) gene has exons coding for activating signaling motifs all other CEACAM1 paralogs contain cytoplasmic exons similar to that of the inhibitory receptor CEACAM1. However, cloning of cDNAs showed that only one CEACAM1 paralog contain functional immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail. Three receptors have acquired a stop codon in the transmembrane domain and two have lost their inhibitory motifs due to alternative splicing events. In addition, alternative splicing eliminated the transmembrane exon sequence of the putative activating receptor, rendering it to a secreted molecule. Transfection of eukaryotic cells with FLAG-tagged alternatively spliced CEACAMs indicates that they can be expressed in vivo. Thus detection of CEACAM41 mRNA in activated PBMC suggests that CEACAM41 is secreted by lymphoid cells upon activation. The results of our study demonstrate that alternative splicing after gene duplication is a potent mechanism to accelerate functional diversification of the equine CEA gene family members. This potent mechanism has created novel CEACAM receptors with unique signaling capacities and secreted CEACAMs which potentially enables equine lymphoid cells to control distantly located immune cells.
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Publication Date: 2018-03-15 PubMed ID: 29544443PubMed Central: PMC5856374DOI: 10.1186/s12862-018-1145-xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores the evolution of the CEA gene family, specifically CEACAM1, in horses and its impact on the immune system. It suggests that gene duplication and alternative splicing are key mechanisms behind this gene family’s expansion and diversification.

Objective and Background

  • The researchers investigated the CEA gene family in the equine genome to understand how its expansion and diversification takes place. The CEA gene family, particularly its CEACAM1 component, is implicated in the immune system and shows varying degrees of expansion across different mammalian species. Underscoring this investigation is the observation that this gene family rapidly evolves in the human genome.

Research Findings

  • The team discovered that the horse genome contains 17 functional genes related to CEACAM1. Of these, nine were identified as secreted molecules and eight were CEACAMs comprising transmembrane and cytoplasmic domain exons.
  • A single gene, labeled as CEACAM41, was found to code for activating signaling motifs. The rest contained cytoplasmic exons similar to those of the inhibitory receptor CEACAM1.
  • Upon cloning cDNA, the researchers observed that only one CEACAM1 paralog contained functional immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail. Moreover, three receptors had acquired a stop codon in the transmembrane domain due to alternative splicing events, while two lost their inhibitory motifs.
  • Alternative splicing also transformed the function of an activating receptor into a secreted molecule by removing the transmembrane exon sequence.

Implications and Conclusion

  • A significant implication from these findings is that discovering the presence of these alternatively spliced CEACAMs in vivo suggests they can be expressed in living organisms. For instance, the detection of CEACAM41 mRNA in activated PBMC hints that this specific gene is secreted by lymphoid cells when activated.
  • This research proposes that alternative splicing following gene duplication is a significant driver of functional diversification within the equine CEA gene family. This method generated new CEACAM receptors with unique signaling abilities and secreted CEACAMs, thereby potentially allowing horse lymphoid cells to control distantly located immune cells.

Cite This Article

APA
Mißbach S, Aleksic D, Blaschke L, Hassemer T, Lee KJ, Mansfeld M, Hänske J, Handler J, Kammerer R. (2018). Alternative splicing after gene duplication drives CEACAM1-paralog diversification in the horse. BMC Evol Biol, 18(1), 32. https://doi.org/10.1186/s12862-018-1145-x

Publication

BMC evolutionary biology
ISSN: 1471-2148
NlmUniqueID: 100966975
Country: England
Language: English
Volume: 18
Issue: 1
Pages: 32
PII: 32

Researcher Affiliations

Mißbach, Sophie
  • Institute of Immunology, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald, Insel Riems, Germany.
  • Plattform Degenerative Erkrankungen, Deutsches Primatenzentrum GmbH, Goettingen, Germany.
Aleksic, Denis
  • Institute of Immunology, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald, Insel Riems, Germany.
Blaschke, Lisa
  • Institute of Immunology, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald, Insel Riems, Germany.
Hassemer, Timm
  • Institute of Immunology, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald, Insel Riems, Germany.
  • Department of Cellular Biochemistry, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Lee, Kyung Jin
  • Institute of Immunology, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald, Insel Riems, Germany.
  • Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Mansfeld, Martin
  • Institute of Immunology, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald, Insel Riems, Germany.
Hänske, Jana
  • Institute of Immunology, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald, Insel Riems, Germany.
Handler, Johannes
  • Clinic for Horses, Veterinary Faculty, Freie Universität Berlin, Oertzenweg 19b, D-14163, Berlin, Germany.
Kammerer, Robert
  • Institute of Immunology, Friedrich-Loeffler-Institut, Suedufer 10, Greifswald, Insel Riems, Germany. Robert.Kammerer@fli.bund.de.
  • Friedrich-Loeffler-Institut, Bundesforschungsinstitut für Tiergesundheit, Federal Research Institute for Animal Health, Südufer 10, D, 17493, Greifswald, Insel Riems, Germany. Robert.Kammerer@fli.bund.de.

MeSH Terms

  • Alternative Splicing / genetics
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / genetics
  • Base Sequence
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Codon / genetics
  • Exons / genetics
  • Gene Duplication
  • Genetic Variation
  • Horses / genetics
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Protein Domains
  • Protein Isoforms / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Sequence Homology, Nucleic Acid

Grant Funding

  • (KF2875802UL2) / Bundesministerium fu00fcr Wirtschaft und Technologie
  • (Contract no. 81170269; Project No. 13.1432.7---001.00) / Gesellschaft fu00fcr internationale Zusammenarbeit
  • HE 6249/4-1 / Deutsche Forschungsgemeinschaft

Conflict of Interest Statement

ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Healthy horses were slaughtered for meat production at the abattoir “Beerwart, Waiblingen”, not as part of this study, however we got permission from the abattoir to use of the tissues for the present study. Further tissue collection was approved by animal use committee of local authorities (Landesamt für Landwirtschaft, Lebensmittelsicherheit und Fischerei (LALLF) Rostock, Germany; 7221.3-2.1-011/13). CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Citations

This article has been cited 3 times.
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