Positive selection signatures in the TLR7 family

Abstract

While adaptive immunity genes evolve rapidly under the influence of positive selection, innate immune system genes are known
to evolve slowly due to strong purifying selection. Among the sensors of the innate immune system, Toll-like receptors (TLRs)
are particularly important due to their ability to recognize and respond to pathogen-associated molecular patterns (PAMP),
such as lipopolysaccharides, peptidoglycans, and nucleic acids from bacteria or viruses. In the present study, we examine
the evolutionary process that has operated on the TLR7 family genes TLR7, TLR8, and TLR9. The results demonstrate that the
average Ka/Ks (the ratio between nonsynonymous and synonymous substitution rates) of each TLR family gene is far lower than
one regardless of estimating methods, supporting previous observations of strong purifying selection in this gene family.
Interestingly, however, analysis of Ka/Ks ratios along the coding regions of TLR7 family genes by sliding-window analysis
reveals a few narrow high peaks (Ka/Ks > 1). The most prominent peak corresponds to a specific region in the ectodomain, which
exists only in the TLR7 family, suggesting that this unique structure of the TLR7 family might have been a target of positive
selection in a variety of lineages. Furthermore, maximum likelihood model tests suggest that positive selection is the best
explanation for a certain fraction of the amino acid substitutions in the TLR9.

KeywordsTLR-Toll-like receptor-PAMP-Pathogen-associated molecular pattern-ECD-Ectodomain-LRR-Leucine-rich receptor-TIR-Toll-IL-1 receptor-MRCA-Most recent common ancestor-LRT-Likelihood ratio test