A History of Recurrent Positive Selection at the Toll-Like Receptor 5 in Primates
| Autor: | Soofia Khan, Gabriela Wlasiuk, Michael W. Nachman, William M. Switzer |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Primates
Genetics Toll-like receptor Mutation Polymorphism Genetic Innate immune system Pan troglodytes Biology medicine.disease_cause Acquired immune system Protein Structure Tertiary Toll-Like Receptor 5 Immunity TLR5 medicine Animals Humans Receptor Molecular Biology Research Articles Phylogeny Ecology Evolution Behavior and Systematics Function (biology) |
| Zdroj: | Molecular Biology and Evolution. 26:937-949 |
| ISSN: | 1537-1719 0737-4038 |
| DOI: | 10.1093/molbev/msp018 |
| Popis: | Many genes involved in immunity evolve rapidly. It remains unclear, however, to what extent pattern-recognition receptors (PRRs) of the innate immune system in vertebrates are subject to recurrent positive selection imposed by pathogens, as suggested by studies in Drosophila, or whether they are evolutionarily constrained. Here, we show that Toll-like receptor 5 (TLR5), a member of the Toll-like receptor family of innate immunity genes that responds to bacterial flagellin, has undergone a history of adaptive evolution in primates. We have identified specific residues that have changed multiple times, sometimes in parallel in primates, and are thus likely candidates for selection. Most of these changes map to the extracellular leucine-rich repeats involved in pathogen recognition, and some are likely to have an effect on protein function due to the radical nature of the amino acid substitutions that are involved. These findings suggest that vertebrate PRRs might show similar patterns of evolution to Drosophila PRRs, in spite of the acquisition of the more complex and specific vertebrate adaptive immune system. At shorter timescales, however, we found no evidence of adaptive evolution in either humans or chimpanzees. In fact, we found that one mutation that abolishes TLR5 function is present at high frequencies in many human populations. Patterns of variation indicate that this mutation is not young, and its high frequency suggests some functional redundancy for this PRR in humans. |
| Databáze: | OpenAIRE |
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