Natural selection in the TLR-related genes in the course of primate evolution

Immunogenetics. 2008 Dec;60(12):727-35. doi: 10.1007/s00251-008-0332-0. Epub 2008 Sep 23.


The innate immune system constitutes the front line of host defense against pathogens. Toll-like receptors (TLRs) recognize molecules derived from pathogens and play crucial roles in the innate immune system. Here, we provide evidence that the TLR-related genes have come under natural selection pressure in the course of primate evolution. We compared the nucleotide sequences of 16 TLR-related genes, including TLRs (TLR1-10), MYD88, TILAP, TICAM1, TICAM2, MD2, and CD14, among seven primate species. Analysis of the non-synonymous/synonymous substitution ratio revealed the presence of both strictly conserved and rapidly evolving regions in the TLR-related genes. The genomic segments encoding the intracellular Toll/interleukin 1 receptor domains, which exhibited lower rates of non-synonymous substitution, have undergone purifying selection. In contrast, TLR4, which carried a high proportion of non-synonymous substitutions in the part of extracellular domain spanning 200 amino acids, was found to have been the suggestive target of positive Darwinian selection in primate evolution. However, sequence analyses from 25 primate species, including eight hominoids, six Old World monkeys, eight New World monkeys, and three prosimians, showed no evidence that the pressure of positive Darwinian selection has shaped the pattern of sequence variations in TLR4 among New World monkeys and prosimians.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics*
  • Amino Acid Sequence
  • Animals
  • Consensus Sequence
  • Evolution, Molecular*
  • Humans
  • Lipopolysaccharide Receptors / genetics*
  • Molecular Sequence Data
  • Multigene Family*
  • Myeloid Differentiation Factor 88 / genetics*
  • Phylogeny
  • Primates / genetics*
  • Protein Structure, Tertiary
  • Selection, Genetic*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Toll-Like Receptors / genetics*


  • Adaptor Proteins, Vesicular Transport
  • Lipopolysaccharide Receptors
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptors