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TLR7 and TLR8 evolution in lagomorphs: different patterns in the different lineages

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Abstract

Toll-like receptors (TLRs) are one of the most ancient and widely studied innate immune receptors responsible for host defense against invading pathogens. Among the known TLRs, TLR7 and TLR8 sense and recognize single-stranded (ss) RNAs with a dynamic evolutionary history. While TLR8 was lost in birds and duplicated in turtles and crocodiles, TLR7 is duplicated in some birds, but in other tetrapods, there is only one copy. In mammals, with the exception of lagomorphs, TLR7 and TLR8 are highly conserved. Here, we aim to study the evolution of TLR7 and TLR8 in mammals, with a special focus in the order Lagomorpha. By searching public sequence databases, conducting evolutionary analysis, and evaluating gene expression, we were able to confirm that TLR8 is absent in hares but widely expressed in the European rabbit. In contrast, TLR7 is absent in the European rabbit and quite divergent in hares. Our results suggest that, in lagomorphs, more in particular in leporids, TLR7 and TLR8 genes have evolved faster than in any other mammalian group. The long history of interaction with viruses and their location in highly dynamic telomeric regions might explain the pattern observed.

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Funding

This work was funded by the Foundation for Science and Technology (FCT), which supported the researcher grants of Joana Abrantes, José Melo-Ferreira and Pedro José Esteves (CEECIND/00078/2017, CEECIND/00372/2018 and 2020.01495.CEECIND/CP1601/CT0005, respectively), and the project UIDB/50027/2020 (Base). This work was supported by the Portuguese Foundation for Science and Technology, under the grant UIDB/04033/2020 (CITAB) and UIDB/CVT/00772/2020 (CECAV), by COMPETE for funding Institute of Biomedicine (iBiMED) under the grant UIDB/04501/2020 and POCI-01-0145-FEDER-007628, and by the Hospital Center of Trás-os-Montes and Alto Douro. The authors thank the Portuguese Foundation for Science and Technology for the Ph.D. grant SFRH/BD/146867/2019.

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Authors and Affiliations

  1. CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus de Vairão, Universidade Do Porto, Vairão, Rua Padre Armando Quintas, nr.7, 4485-661, Vairão, Portugal

    Fabiana Neves, João Pedro Marques, Helena Areal, José Melo-Ferreira, Joana Abrantes & Pedro José Esteves

  2. BIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Campus de Vairão, 4485-661, Vairão, Portugal

    Fabiana Neves, João Pedro Marques, Helena Areal, José Melo-Ferreira, Joana Abrantes & Pedro José Esteves

  3. Departamento de Biologia, Faculdade de Ciências, Universidade Do Porto, 4099-002, Porto, Portugal

    João Pedro Marques, José Melo-Ferreira, Joana Abrantes & Pedro José Esteves

  4. CITAB – Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-Os-Montes and Alto Douro, Vila Real, Portugal

    Patrícia Pinto-Pinho & Bruno Colaço

  5. Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine - iBiMED, University of Aveiro, Aveiro, Portugal

    Patrícia Pinto-Pinho & Margarida Fardilha

  6. Genetics/Andrology Laboratory, Centro Hospitalar de Trás-Os-Montes E Alto Douro, E.P.E, Vila Real, Portugal

    Patrícia Pinto-Pinho

  7. CECAV – Animal and Veterinary Research Centre UTAD, University of Trás-Os-Montes and Alto Douro, Vila Real, Portugal

    Bruno Colaço

  8. ISEM, Univ Montpellier, CNRS, EPHE, IRD, 34095, Montpellier, France

    João Pedro Marques

  9. CITS – Center of Investigation in Health Technologies, CESPU, 4585-116, Gandra, Portugal

    Pedro José Esteves

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  1. Fabiana Neves
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  2. João Pedro Marques
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  3. Helena Areal
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  4. Patrícia Pinto-Pinho
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  5. Bruno Colaço
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  6. José Melo-Ferreira
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  7. Margarida Fardilha
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  8. Joana Abrantes
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  9. Pedro José Esteves
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Contributions

JA and PJE designed the study and, in collaboration with JM-F and MF, also designed the experiments. FN, PP-P, and BC performed experiments. FN, JPM, HA, PP-P, BC, JM-F, MF JA, and PJE analyzed the data. FN wrote the manuscript with contributions from all the authors.

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Correspondence to Fabiana Neves.

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This study was approved and licensed by the Portuguese competent authority for animal welfare, the Directorate-General for Food and Veterinary (permit number: 010532/2018). All experimental procedures were performed following DR 1.ª série- N.º151-7 of August 2013 and the EU Directive 2010/63/EU for animal experiments. The study was also approved by the Ethics and Internal Review Board of the Hospital Infante D. Pedro E.P.E. (Aveiro, Portugal) (Process number: 36/AO; Approved on 14 April 2015) and was conducted under the Declaration of Helsinki (as revised in Declaration of Helsinki 2000 – WMA – The World Medical Association, 2000). All healthy donors were provided with information regarding the study and written consent was obtained before study enrollment.

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Joana Abrantes and Pedro J. Esteves share the senior authorship.

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Neves, F., Marques, J.P., Areal, H. et al. TLR7 and TLR8 evolution in lagomorphs: different patterns in the different lineages. Immunogenetics 74, 475–485 (2022). https://doi.org/10.1007/s00251-022-01262-9

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