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Journal of Molecular Evolution

, Volume 80, Issue 2, pp 130–141 | Cite as

Adaptive Evolution of Formyl Peptide Receptors in Mammals

  • Yoshinori Muto
  • Stéphane Guindon
  • Toshiaki Umemura
  • László Kőhidai
  • Hiroshi Ueda
Original Article

Abstract

The formyl peptide receptors (FPRs) are a family of chemoattractant receptors with important roles in host defense and the regulation of inflammatory reactions. In humans, three FPR paralogs have been identified (FPR1, FPR2, and FPR3) and may have functionally diversified by gene duplication and adaptive evolution. However, the evolutionary mechanisms operating in the diversification of FPR family genes and the changes in selection pressures have not been characterized to date. Here, we have made a comprehensive evolutionary analysis of FPR genes from mammalian species. Phylogenetic analysis showed that an early duplication was responsible for FPR1 and FPR2/FPR3 splitting, and FPR3 originated from the latest duplication event near the origin of primates. Codon-based tests of positive selection reveal interesting patterns in FPR1 and FPR2 versus FPR3, with the first two genes showing clear evidence of positive selection at some sites while the majority of them evolve under strong negative selection. In contrast, our results suggest that the selective pressure may be relaxed in the FPR3 lineage. Of the six amino acid sites inferred to evolve under positive selection in FPR1 and FPR2, four sites were located in extracellular loops of the protein. The electrostatic potential of the extracellular surface of FPR might be affected more frequently with amino acid substitutions in positively selected sites. Thus, positive selection of FPRs among mammals may reflect a link between changes in the sequence and surface structure of the proteins and is likely to be important in the host’s defense against invading pathogens.

Keywords

Molecular evolution Formyl peptide receptor Positive selection Mammal 

Notes

Conflict of interest

The authors declare that they have no conflict of interests.

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Yoshinori Muto
    • 1
    • 2
  • Stéphane Guindon
    • 3
  • Toshiaki Umemura
    • 4
  • László Kőhidai
    • 5
  • Hiroshi Ueda
    • 1
    • 6
  1. 1.United Graduate School of Drug Discovery and Medical Information SciencesGifu UniversityGifuJapan
  2. 2.Department of Functional BioscienceGifu University School of MedicineGifuJapan
  3. 3.Department of StatisticsThe University of AucklandAucklandNew Zealand
  4. 4.Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  5. 5.Department of Genetics, Cell and ImmunobiologySemmelweis UniversityBudapestHungary
  6. 6.Department of Biomolecular Science, Faculty of EngineeringGifu UniversityGifuJapan

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