Contrasting patterns of polymorphism and selection in bacterial-sensing toll-like receptor 4 in two house mouse subspecies
Article first published online: 20 JUN 2014
© 2014 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Ecology and Evolution
Volume 4, Issue 14, pages 2931–2944, July 2014
How to Cite
Ecology and Evolution 2014; 4(14):2931–2944
- Issue published online: 21 JUL 2014
- Article first published online: 20 JUN 2014
- Manuscript Accepted: 14 MAY 2014
- Manuscript Revised: 9 MAY 2014
- Manuscript Received: 13 JAN 2014
- Czech Science Foundation. Grant Number: 206/08/0640
- Ministry of Education, Youth and Sports of the Czech Republic, NextGenProject: Next-generation technologies in evolutionary genetics. Grant Number: CZ.1.07/2.3./20.0303
- Adaptive evolution;
- arms race;
- directional selection;
- host–pathogen interaction;
- Mus musculus ;
- parasite-mediated selection;
- pattern-recognition receptors
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.