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Contrasting patterns of polymorphism and selection in bacterial-sensing toll-like receptor 4 in two house mouse subspecies

Authors

  • Alena Fornuskova,

    Corresponding author
    1. Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, Brno, Czech Republic
    2. Department of Botany and Zoology, Faculty of Science, Masaryk University, Brno, Czech Republic
    3. Centre de Biologie pour la Gestion des Populations (CBGP), Institut National de la Recherche Agronomique (INRA), Campus International de Baillarguet, Montferrier-sur-Lez, France
    • Correspondence

      Alena Fornůsková

      Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, Research Facility Studenec, 675 02 Studenec 122, Czech Republic.

      Tel: +420 560 590 621;

      E-mail: fornuskova@ivb.cz

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  • Josef Bryja,

    1. Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, Brno, Czech Republic
    2. Department of Botany and Zoology, Faculty of Science, Masaryk University, Brno, Czech Republic
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  • Michal Vinkler,

    1. Department of Zoology, Faculty of Science, Charles University in Prague, Prague, Czech Republic
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  • Miloš Macholán,

    1. Laboratory of Mammalian Evolutionary Genetics, Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Brno, Czech Republic
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  • Jaroslav Piálek

    1. Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, Brno, Czech Republic
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Abstract

Detailed investigation of variation in genes involved in pathogen recognition is crucial for understanding co-evolutionary processes between parasites and their hosts. Triggering immediate innate response to invading microbes, Toll-like receptors (TLRs) belong presently among the best-studied receptors of vertebrate immunity. TLRs exhibit remarkable interspecific variation and also intraspecific polymorphism is well documented. In humans and laboratory mice, several studies have recently shown that single amino acid substitution may significantly alter receptor function. Unfortunately, data concerning polymorphism in free-living species are still surprisingly scarce. In this study, we analyzed the polymorphism of Toll-like receptor 4 (Tlr4) over the Palearctic range of house mouse (Mus musculus). Our results reveal contrasting evolutionary patterns between the two recently (0.5 million years ago) diverged house mouse subspecies: M. m. domesticus (Mmd) and M. m. musculus (Mmm). Comparison with cytochrome b indicates strong directional selection in Mmd Tlr4. Throughout the whole Mmd western Palaearctic region, a single variant of the ligand-binding region is spread, encoded mainly by one dominant haplotype (71% of Mmd). In contrast, Tlr4 in Mmm is much more polymorphic with several haplotypes at intermediate frequencies. Moreover, we also found clear signals of recombination between two principal haplogroups in Mmm, and we identified eight sites under positive selection in our dataset. Our results suggest that observed differences in Tlr4 diversity may be attributed to contrasting parasite-mediated selection acting in the two subspecies.

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