title: Comparative genomics and evolution of the alpha-defensin multigene family in primates.
abstract: Defensin genes encode small cationic antimicrobial peptides that form an important part of the innate immune system. They are divided into three families, alpha (α), beta (β), and theta (), according to arrangement of the disulfide bonding pattern between cysteine residues. Considering the functional importance of defensins, investigators have studied the evolution and the genomic organization of defensin genes. However, these studies have been restricted mainly to β-defensins. To understand the evolutionary dynamics of α-defensin genes among primates, we identified the α-defensin repertoires in human, chimpanzee, orangutan, macaque, and marmoset. The α-defensin genes in primates can be classified into three phylogenetic classes (class I, II, and III). The presence of all three classes in the marmoset indicates that their divergence occurred before the separation of New World and Old World monkeys. Comparative analysis of the α-defensin genomic clusters suggests that the makeup of the α-defensin gene repertoires between primates is quite different, as their genes have undergone dramatic birth-and-death evolution. Analysis of the encoded peptides of the α-defensin genes indicates that despite the overall high level of sequence divergence, certain amino acid residues or motifs are conserved within and between the three phylogenetic classes. The evolution of α-defensins in primates, therefore, appears to be governed by two opposing evolutionary forces. One force stabilizes specific amino acid residues and motifs to preserve the functional and structural integrity of the molecules and the other diversifies the sequences generating molecules with a wide range of activities against a large number of pathogens.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory Vaccine Center, School of Medicine, Emory University, USA. sdas8@emory.edu
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Das
authors.forename: Nikolas
authors.initials: N
authors.lastname: Nikolaidis
authors.forename: Hiroki
authors.initials: H
authors.lastname: Goto
authors.forename: Chelsea
authors.initials: C
authors.lastname: McCallister
authors.forename: Jianxu
authors.initials: J
authors.lastname: Li
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hirano
authors.forename: Max D
authors.initials: MD
authors.lastname: Cooper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D040461:Gene Components; D023281:Genomics; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010802:Phylogeny; D011323:Primates / Q000235:genetics*; D011487:Protein Conformation; D017510:Protein Folding; D012641:Selection, Genetic; D016415:Sequence Alignment; D013045:Species Specificity; D055672:Static Electricity; D023084:alpha-Defensins / Q000235:genetics*
chemical_list: D023084:alpha-Defensins
references.citation: J Leukoc Biol. 1992 Jun;51(6):634-9
references.pmid: 1613398
references.citation: Biol Reprod. 2005 Dec;73(6):1243-52
references.pmid: 16079310
references.citation: Proteins. 2008 Feb 15;70(3):611-25
references.pmid: 17876813
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10866-71
references.pmid: 11005860
references.citation: Blood. 1992 Mar 15;79(6):1538-44
references.pmid: 1339298
references.citation: BMC Bioinformatics. 2006 Oct 25;7:474
references.pmid: 17064419
references.citation: Nat Rev Immunol. 2003 Sep;3(9):710-20
references.pmid: 12949495
references.citation: J Biol Chem. 2009 Mar 13;284(11):6826-31
references.pmid: 19106102
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11030-5
references.pmid: 15258291
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7799-806
references.pmid: 9223266
references.citation: FEBS Lett. 2009 Aug 6;583(15):2507-12
references.pmid: 19589339
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6039-44
references.pmid: 15824306
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12235-42
references.pmid: 17640887
references.citation: J Clin Invest. 1988 Jun;81(6):1829-35
references.pmid: 3290255
references.citation: J Mol Biol. 2008 Sep 19;381(5):1281-91
references.pmid: 18616948
references.citation: Infect Immun. 2008 Dec;76(12):5883-91
references.pmid: 18852242
references.citation: Science. 2002 Nov 1;298(5595):995-1000
references.pmid: 12351674
references.citation: Bioinformatics. 2000 Jun;16(6):566-7
references.pmid: 10980157
references.citation: BMC Evol Biol. 2008 Apr 16;8:113
references.pmid: 18416833
references.citation: BMC Genomics. 2004 Aug 13;5(1):56
references.pmid: 15310403
references.citation: Physiol Genomics. 2004 Dec 15;20(1):1-11
references.pmid: 15494476
references.citation: Curr Protein Pept Sci. 2004 Oct;5(5):365-71
references.pmid: 15544531
references.citation: Trends Immunol. 2002 Jun;23(6):291-6
references.pmid: 12072367
references.citation: J Biol Chem. 2008 Dec 19;283(51):35869-77
references.pmid: 18930922
references.citation: Mol Biol Evol. 2004 Mar;21(3):498-505
references.pmid: 14694072
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18129-34
references.pmid: 16330776
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W270-5
references.pmid: 18508808
references.citation: Mol Biol Evol. 2007 Aug;24(8):1586-91
references.pmid: 17483113
references.citation: Mol Biol Evol. 2004 May;21(5):819-27
references.pmid: 14963090
references.citation: Biochemistry. 2000 Dec 26;39(51):15757-64
references.pmid: 11123900
references.citation: Hum Mol Genet. 2001 Oct 1;10(21):2373-83
references.pmid: 11689484
references.citation: J Mol Biol. 1982 May 5;157(1):105-32
references.pmid: 7108955
references.citation: Mol Biol Evol. 1987 Jul;4(4):406-25
references.pmid: 3447015
references.citation: Science. 1999 Oct 15;286(5439):525-8
references.pmid: 10521347
references.citation: Mol Biol Evol. 2010 Jan;27(1):113-20
references.pmid: 19744999
references.citation: Curr Opin Immunol. 1994 Aug;6(4):584-9
references.pmid: 7946046
references.citation: Mol Biol Evol. 2009 May;26(5):1179-89
references.pmid: 19246621
references.citation: Science. 1999 Oct 15;286(5439):498-502
references.pmid: 10521339
references.citation: Mol Biol Evol. 1994 May;11(3):469-82
references.pmid: 8015440
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16647-52
references.pmid: 18940927
references.citation: Mol Biol Evol. 2005 Apr;22(4):1107-18
references.pmid: 15689528
references.citation: Genome Biol. 2003;4(5):R31
references.pmid: 12734011
references.citation: Genes Immun. 2003 Jun;4(4):251-7
references.pmid: 12761560
references.citation: Genetics. 2000 May;155(1):431-49
references.pmid: 10790415
references.citation: J Leukoc Biol. 2009 Oct;86(4):941-8
references.pmid: 19477909
references.citation: Bioinformatics. 2006 Jan 15;22(2):195-201
references.pmid: 16301204
references.citation: BMC Evol Biol. 2005 May 18;5:32
references.pmid: 15904491
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20421-6
references.pmid: 18077390
references.citation: Mol Biol Evol. 2003 Mar;20(3):460-70
references.pmid: 12644567
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4830-5
references.pmid: 15772169
references.citation: Mol Biol Evol. 2007 Aug;24(8):1596-9
references.pmid: 17488738
references.citation: Curr Opin Immunol. 2007 Aug;19(4):385-91
references.pmid: 17702560
references.citation: Dev Comp Immunol. 2007;31(10):963-7
references.pmid: 17367857
references.citation: Mol Biol Evol. 2001 Apr;18(4):503-13
references.pmid: 11264401
references.citation: Immunogenetics. 2008 Jan;60(1):47-55
references.pmid: 18196235
references.citation: Nature. 2005 Sep 1;437(7055):94-100
references.pmid: 16136133
references.citation: Mol Phylogenet Evol. 2006 Nov;41(2):384-94
references.pmid: 16815047
references.citation: Genome Res. 2005 Dec;15(12):1787-97
references.pmid: 16339377
references.citation: Am J Hum Genet. 1999 Jan;64(1):24-30
references.pmid: 9915939
references.citation: Protein Sci. 2006 Dec;15(12):2749-60
references.pmid: 17088326
references.citation: Mol Biol Evol. 2003 Apr;20(4):601-9
references.pmid: 12679545
references.citation: Blood. 1995 Feb 15;85(4):1095-103
references.pmid: 7849297
references.citation: Nat Rev Immunol. 2006 Jun;6(6):447-56
references.pmid: 16724099
references.citation: Infect Immun. 2004 Mar;72(3):1470-8
references.pmid: 14977952
references.citation: Antimicrob Agents Chemother. 2008 Mar;52(3):944-53
references.pmid: 18160518
references.citation: Genome Res. 1997 Mar;7(3):250-61
references.pmid: 9074928
references.citation: Mol Biol Evol. 2004 Sep;21(9):1704-11
references.pmid: 15175411