Toll-like receptor 4 genetic diversity among pig populations

S. Palermo, E. Capra, M. Torremorell, M. Dolzan, R. Davoli, C. S. Haley, E. Giuffra

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The transmembrane glycoprotein encoded by the Toll-like receptor 4 gene (TLR4) acts as the transducing subunit of the lipopolysaccharide receptor complex of mammals, which is a major sensor of infections by Gram-negative bacteria. As variation in TLR4 may alter host immune response to lipopolysaccharide, the association between TLR4 polymorphisms and immune traits of the respiratory and gut systems has important implications for livestock. Here, a sequence dataset from 259 animals belonging to commercial and traditional European pig populations, consisting of 4305 bp of TLR4, including the full transcribed region, a portion of intron 2 and the putative promoter region, was used to explore genetic variation segregating at the TLR4 locus. We identified 34 single nucleotide polymorphisms, 17 in the coding sequence and 17 in the non-coding region. Five non-synonymous mutations clustered within, or in close proximity to, the hypervariable domain of exon 3. In agreement with studies in other mammals, a major exon 3 haplotype segregated at high frequency in the whole sample of 259 pigs, while variants carrying non-synonymous substitutions showed frequencies ranging between 0.6% and 8.7%. Although results on exon 3 provided suggestive evidence for purifying selection occurring at the porcine TLR4 gene, the analysis of both coding and non-coding regions highlighted the fact that demographic factors strongly influence the tests of departure from neutrality. The phylogenetic analysis of TLR4 identified three clusters of variation (ancestral, Asian, European), supporting the evidence of Asian introgression in European main breeds and the well documented history of pig breed domestication previously identified by mtDNA analysis.

Original languageEnglish (US)
Pages (from-to)289-299
Number of pages11
JournalAnimal Genetics
Volume40
Issue number3
DOIs
StatePublished - Jun 1 2009

Keywords

  • Haplotype
  • Innate immunity
  • Population
  • Selection
  • Single nucleotide polymorphism
  • Toll-like receptor 4

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