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Convergent evolution of IL-6 in two leporids (Oryctolagus and Pentalagus) originated an extended protein

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Abstract

Interleukin 6 (IL-6) is a class-I helical cytokine with a broad spectrum of biological activities and a gene structure conserved throughout vertebrates, with five coding exons. IL-6 from European rabbits belonging to the subspecies Oryctolagus cuniculus cuniculus was previously shown to differ from other mammals by extending an additional 27 amino acids. However, in other leporids (Sylvilagus spp and Lepus spp) that diverged from the European rabbit ~12 million years ago this mutation was not present. In this study, we extended the study of IL-6 for the Oryctolagus cuniculus algirus subspecies and five additional lagomorphs’ genera (Brachylagus, Bunolagus, Pentalagus, Romerolagus, and Ochotona). We confirmed the presence of the mutated stop codon in both O. c. cuniculus and O. c. algirus. We found that the typical stop codon is present in Sylvilagus bachmani and Lepus europaeus, in agreement with previous reports, but also in Bunolagus, Brachylagus, and Ochotona. Remarkably, in Pentalagus we detected a deletion of the stop codon causing an extension of IL-6 for 17 extra residues. Our results indicate that the IL-6 extension in those species occurred by two independent events: one occurred between 2 and 8 million years ago in the ancestral of the Oryctolagus subspecies, and the other occurred in a Pentalagus ancestral at a maximum of 9 million years ago. The absence of this IL-6 extension in Bunolagus, sister genus of Oryctolagus, shows that this evolutionary event happened by convergence suggesting some functional relevance.

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Acknowledgments

This work was partially funded by FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the Programa Operacional Factores de Competitividade (COMPETE program; FCOMP-01-0124-FEDER-028286) and Portuguese national funds through FCT (Fundação para a Ciência e a Tecnologia; research project PTDC/BIO-ANM/3963/2012)–Quadro de Referência Estratégico Nacional (QREN) funds from the European Social Fund and Portuguese Ministério da Educação e Ciência. FCT also supported the doctoral grants of FN and AP (refs.: SFRH/BD/81916/2011 and SFRH/BD/71252/2010) and the FCT Investigator grant of JA (ref.: IF/01396/2013). “Genomics Applied To Genetic Resources” cofinanced by North Portugal Regional Operational Programme 2007/2013 (ON.2–O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF), also supported this work.

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Authors and Affiliations

  1. CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, InBIO, Laboratório Associado, Campus Agrário de Vairão, Vairão, Portugal

    Fabiana Neves, Joana Abrantes, Ana Pinheiro, Tereza Almeida & Pedro J Esteves

  2. UMIB/UP–Unidade Multidisciplinar de Investigação Biomédica/Universidade do Porto, Porto, Portugal

    Fabiana Neves & Paulo P. Costa

  3. Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, 4169-007, Porto, Portugal

    Ana Pinheiro & Pedro J Esteves

  4. SaBio-IREC (CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13071, Ciudad Real, Spain

    Ana Pinheiro

  5. Departamento de Genética, CSPGF, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal

    Paulo P. Costa

  6. CITS-Centro de Investigação em Tecnologias de Saúde, CESPU, Gandra, Portugal

    Pedro J Esteves

  7. CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, Rua Padre Armando Quintas, nr.7, 4485-661, Vairão, Portugal

    Pedro J Esteves

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  1. Fabiana Neves
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  2. Joana Abrantes
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  4. Tereza Almeida
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  6. Pedro J Esteves
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Correspondence to Pedro J Esteves.

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Neves, F., Abrantes, J., Pinheiro, A. et al. Convergent evolution of IL-6 in two leporids (Oryctolagus and Pentalagus) originated an extended protein. Immunogenetics 66, 589–595 (2014). https://doi.org/10.1007/s00251-014-0787-0

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  • DOI: https://doi.org/10.1007/s00251-014-0787-0

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