title: Adaptive evolution of formyl peptide receptors in mammals.
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.
authors: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1, Yanagido, Gifu, 501-1193, Japan, ymuto@gifu-u.ac.jp.
authors: Yoshinori
authors: Y
authors: Muto
authors: Stéphane
authors: S
authors: Guindon
authors: Toshiaki
authors: T
authors: Umemura
authors: László
authors: L
authors: Kőhidai
authors: Hiroshi
authors: H
authors: Ueda
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D008322:Mammals / Q000235:genetics*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D044042:Receptors, Formyl Peptide / Q000737:chemistry / Q000235:genetics*
chemical_list: D044042:Receptors, Formyl Peptide
references: PLoS One. 2010 Feb 11;5(2):e9175
references: 20161793
references: Genetics. 2000 May;155(1):431-49
references: 10790415
references: J Immunol. 1975 Jun;114(6):1831-7
references: 165239
references: Pharmacol Rev. 2009 Jun;61(2):119-61
references: 19498085
references: Mol Biol Evol. 2002 Jan;19(1):49-57
references: 11752189
references: J Genet Genomics. 2010 Dec;37(12):771-8
references: 21193155
references: Mol Biol Evol. 1987 Jul;4(4):406-25
references: 3447015
references: J Mol Evol. 2011 Dec;73(5-6):257-65
references: 22218679
references: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
references: 11517324
references: J Neurosci Methods. 2009 Jun 30;181(1):1-5
references: 19447501
references: BMC Bioinformatics. 2008 Jan 23;9:40
references: 18215316
references: Genetics. 1998 Mar;148(3):929-36
references: 9539414
references: Trends Immunol. 2006 Aug;27(8):381-6
references: 16814608
references: Nature. 2009 May 28;459(7246):574-7
references: 19387439
references: Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12957-62
references: 15326304
references: Genome Res. 2004 May;14(5):929-33
references: 15123588
references: Mol Biol Evol. 2011 Oct;28(10):2731-9
references: 21546353
references: Evolution. 1985 Jul;39(4):783-791
references: 28561359
references: Mol Biol Evol. 1996 May;13(5):685-90
references: 8676743
references: J Immunol. 2008 Jul 15;181(2):1429-37
references: 18606697
references: Mol Interv. 2007 Feb;7(1):17-25
references: 17339603
references: Mol Biol Evol. 2007 Aug;24(8):1586-91
references: 17483113
references: Mol Biol Evol. 2005 Apr;22(4):1107-18
references: 15689528
references: Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9842-7
references: 19497865
references: Mol Pharmacol. 2005 May;67(5):1414-25
references: 15687224
references: Nat Protoc. 2010 Apr;5(4):725-38
references: 20360767
references: J Mol Model. 2012 Jun;18(6):2831-43
references: 22127612
references: J Leukoc Biol. 2002 Oct;72(4):628-35
references: 12377930
references: Mamm Genome. 2011 Oct;22(9-10):621-33
references: 21717223
references: J Mol Evol. 2008 May;66(5):446-56
references: 18414925
references: Mol Pharmacol. 2013 Feb;83(2):389-98
references: 23160941
references: Ann N Y Acad Sci. 2005 Apr;1040:89-94
references: 15891011
references: J Biol Chem. 2000 Dec 15;275(50):39012-7
references: 10960471
references: Mol Biol Evol. 2014 Feb;31(2):484-95
references: 24132121
references: Biosci Biotechnol Biochem. 2007 May;71(5):1198-202
references: 17485829
references: Pharmacol Ther. 1997;74(1):73-102
references: 9336017
references: Trends Pharmacol Sci. 2010 Jun;31(6):266-76
references: 20483490
references: J Biol Chem. 2011 Jul 29;286(30):26718-31
references: 21543323
references: Brief Bioinform. 2008 Jul;9(4):286-98
references: 18372315
references: J Biol Chem. 1993 Aug 25;268(24):18167-75
references: 8349692
references: Arch Biochem Biophys. 2011 Dec 15;516(2):121-7
references: 22005393
references: Nat Med. 1998 Nov;4(11):1302-7
references: 9809555
references: Gen Comp Endocrinol. 2005 May 15;142(1-2):94-101
references: 15862553
references: J Exp Med. 2005 Jan 3;201(1):83-93
references: 15623572
references: Syst Biol. 2010 May;59(3):307-21
references: 20525638
references: Nat Methods. 2012 Jul 30;9(8):772
references: 22847109
references: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references: 9254694
references: J Mol Evol. 2008 Apr;66(4):384-94
references: 18347751
references: Immunogenetics. 1996;44(6):446-52
references: 8824156
references: J Immunol. 2004 Nov 1;173(9):5739-48
references: 15494526
references: Mol Pharmacol. 2005 Nov;68(5):1301-10
references: 16118363
references: Trends Immunol. 2002 Nov;23(11):541-8
references: 12401407