title: Evolution of a new function by degenerative mutation in cephalochordate steroid receptors.
abstract: Gene duplication is the predominant mechanism for the evolution of new genes. Major existing models of this process assume that duplicate genes are redundant; degenerative mutations in one copy can therefore accumulate close to neutrally, usually leading to loss from the genome. When gene products dimerize or interact with other molecules for their functions, however, degenerative mutations in one copy may produce repressor alleles that inhibit the function of the other and are therefore exposed to selection. Here, we describe the evolution of a duplicate repressor by simple degenerative mutations in the steroid hormone receptors (SRs), a biologically crucial vertebrate gene family. We isolated and characterized the SRs of the cephalochordate Branchiostoma floridae, which diverged from other chordates just after duplication of the ancestral SR. The B. floridae genome contains two SRs: BfER, an ortholog of the vertebrate estrogen receptors, and BfSR, an ortholog of the vertebrate receptors for androgens, progestins, and corticosteroids. BfSR is specifically activated by estrogens and recognizes estrogen response elements (EREs) in DNA; BfER does not activate transcription in response to steroid hormones but binds EREs, where it competitively represses BfSR. The two genes are partially coexpressed, particularly in ovary and testis, suggesting an ancient role in germ cell development. These results corroborate previous findings that the ancestral steroid receptor was estrogen-sensitive and indicate that, after duplication, BfSR retained the ancestral function, while BfER evolved the capacity to negatively regulate BfSR. Either of two historical mutations that occurred during BfER evolution is sufficient to generate a competitive repressor. Our findings suggest that after duplication of genes whose functions depend on specific molecular interactions, high-probability degenerative mutations can yield novel functions, which are then exposed to positive or negative selection; in either case, the probability of neofunctionalization relative to gene loss is increased compared to existing models.
authors.affiliation: Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Jamie T
authors.initials: JT
authors.lastname: Bridgham
authors.forename: Justine E
authors.initials: JE
authors.lastname: Brown
authors.forename: Adriana
authors.initials: A
authors.lastname: Rodríguez-Marí
authors.forename: Julian M
authors.initials: JM
authors.lastname: Catchen
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Thornton
mesh_terms: D000818:Animals; D002816:Chordata, Nonvertebrate / Q000235:genetics*; D019143:Evolution, Molecular; D020440:Gene Duplication; D008957:Models, Genetic; D009154:Mutation; D010802:Phylogeny; D011960:Receptors, Estrogen / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D011987:Receptors, Steroid
references.citation: Proc Natl Acad Sci U S A. 1998 May 26;95(11):5998-6003
references.pmid: 9600906
references.citation: Curr Opin Genet Dev. 1996 Dec;6(6):715-22
references.pmid: 8994842
references.citation: Genetics. 2005 Dec;171(4):1455-61
references.pmid: 15965245
references.citation: Hum Reprod Update. 2000 May-Jun;6(3):225-36
references.pmid: 10874567
references.citation: Syst Biol. 2007 Feb;56(1):113-24
references.pmid: 17366141
references.citation: Philos Trans R Soc Lond B Biol Sci. 2002 Apr 29;357(1420):531-44
references.pmid: 12028790
references.citation: Nature. 2006 Nov 2;444(7115):85-8
references.pmid: 17051155
references.citation: Annu Rev Biochem. 2005;74:867-900
references.pmid: 15954844
references.citation: DNA Cell Biol. 2000 Oct;19(10):589-99
references.pmid: 11058961
references.citation: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2950-4
references.pmid: 8159686
references.citation: Science. 2000 Jul 7;289(5476):119-23
references.pmid: 10884226
references.citation: J Endocrinol. 2006 Jul;190(1):17-28
references.pmid: 16837607
references.citation: Proc Natl Acad Sci U S A. 2001 May 8;98(10):5671-6
references.pmid: 11331759
references.citation: Endocrinology. 2007 Aug;148(8):3554-65
references.pmid: 17446181
references.citation: Science. 2000 Nov 10;290(5494):1151-5
references.pmid: 11073452
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8396-401
references.pmid: 15159545
references.citation: Genetica. 2003 Jul;118(2-3):279-94
references.pmid: 12868616
references.citation: Endocrinology. 2003 Oct;144(10):4226-36
references.pmid: 12959971
references.citation: Nature. 2006 Feb 23;439(7079):965-8
references.pmid: 16495997
references.citation: Mol Biol Evol. 2008 May;25(5):809-20
references.pmid: 18296701
references.citation: Genome Res. 2008 Jul;18(7):1100-11
references.pmid: 18562680
references.citation: Biochemistry. 2003 Jun 3;42(21):6427-35
references.pmid: 12767224
references.citation: Nature. 1987 Jan 1-7;325(6099):75-8
references.pmid: 3025750
references.citation: Curr Opin Cell Biol. 1999 Apr;11(2):255-60
references.pmid: 10209153
references.citation: Science. 1988 May 13;240(4854):889-95
references.pmid: 3283939
references.citation: Development. 2003 Dec;130(24):5903-14
references.pmid: 14561632
references.citation: Evolution. 2006 May;60(5):881-92
references.pmid: 16817530
references.citation: Trends Immunol. 2003 Jul;24(7):387-94
references.pmid: 12860530
references.citation: Gene Expr Patterns. 2005 Jun;5(5):655-67
references.pmid: 15939378
references.citation: BMC Evol Biol. 2007 Feb 16;7:24
references.pmid: 17306029
references.citation: Science. 2003 Sep 19;301(5640):1714-7
references.pmid: 14500980
references.citation: Proc Natl Acad Sci U S A. 2007 May 15;104(20):8275-80
references.pmid: 17485680
references.citation: Mol Cell Biol. 1995 Feb;15(2):1005-13
references.pmid: 7823916
references.citation: Nature. 2004 Jun 10;429(6992):661-4
references.pmid: 15190353
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10751-6
references.pmid: 11005855
references.citation: Genome Res. 1999 Jul;9(7):629-38
references.pmid: 10413401
references.citation: Annu Rev Genet. 1997;31:91-111
references.pmid: 9442891
references.citation: Nature. 2006 Nov 9;444(7116):171-8
references.pmid: 17086204
references.citation: Mol Biol Evol. 2004 Oct;21(10):1923-37
references.pmid: 15229292
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9118-23
references.pmid: 16754868
references.citation: Mol Endocrinol. 1997 Sep;11(10):1476-85
references.pmid: 9280063
references.citation: Mol Cell. 1999 Apr;3(4):513-9
references.pmid: 10230404
references.citation: Genetics. 1999 Apr;151(4):1531-45
references.pmid: 10101175
references.citation: Science. 1991 May 24;252(5009):1078-9
references.pmid: 2031181
references.citation: Nature. 1997 Oct 16;389(6652):753-8
references.pmid: 9338790
references.citation: Mol Endocrinol. 1993 Oct;7(10):1244-55
references.pmid: 8264658
references.citation: Science. 2005 Feb 25;307(5713):1279-82
references.pmid: 15653464
references.citation: Nat Genet. 2004 May;36(5):492-6
references.pmid: 15107850
references.citation: Vitam Horm. 2004;68:1-48
references.pmid: 15193450
references.citation: Plant Cell. 2004 Jul;16(7):1679-91
references.pmid: 15208398
references.citation: Plant Physiol. 2007 Jun;144(2):662-72
references.pmid: 17098856
references.citation: Genome Res. 2002 Nov;12(11):1625-41
references.pmid: 12421749
references.citation: Syst Biol. 2003 Oct;52(5):696-704
references.pmid: 14530136
references.citation: J Biol Chem. 2001 Nov 16;276(46):42684-91
references.pmid: 11553641
references.citation: Dev Genes Evol. 2003 Jun;213(5-6):235-44
references.pmid: 12743820
references.citation: Mol Biol Evol. 1993 Nov;10(6):1360-9
references.pmid: 8277859
references.citation: Nat Rev Genet. 2002 Nov;3(11):827-37
references.pmid: 12415313
references.citation: BMC Evol Biol. 2007 Jan 18;7:2
references.pmid: 17233905
references.citation: Bioinformatics. 2003 Aug 12;19(12):1572-4
references.pmid: 12912839
references.citation: J Am Soc Nephrol. 2006 Jul;17(7):1759-1764
references.pmid: 37000978
references.citation: Proc Biol Sci. 2003 Mar 7;270(1514):457-66
references.pmid: 12641899
references.citation: Gen Comp Endocrinol. 2007 Aug-Sep;153(1-3):47-56
references.pmid: 17470371
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):635-40
references.pmid: 18182486
references.citation: Biochem Biophys Res Commun. 1999 Oct 14;264(1):230-4
references.pmid: 10527870
references.citation: Genetics. 2005 Feb;169(2):1157-64
references.pmid: 15654095
references.citation: Cell. 2005 Feb 11;120(3):343-55
references.pmid: 15707893
references.citation: Nature. 1996 Jun 20;381(6584):694-6
references.pmid: 8649513
references.citation: BMC Bioinformatics. 2004 Aug 19;5:113
references.pmid: 15318951
references.citation: Dev Biol. 2006 Dec 1;300(1):90-107
references.pmid: 17054934
references.citation: Nature. 2004 Oct 21;431(7011):980-4
references.pmid: 15496922
references.citation: Hum Reprod. 2007 Jul;22(7):1885-92
references.pmid: 17504822
references.citation: Mol Biol Evol. 2008 Jun;25(6):1054-66
references.pmid: 18319244
references.citation: Gen Comp Endocrinol. 2003 Aug;133(1):38-49
references.pmid: 12899845
references.citation: Trends Biochem Sci. 2008 May;33(5):220-9
references.pmid: 18406148
references.citation: Nat Rev Genet. 2007 Aug;8(8):610-8
references.pmid: 17637733
references.citation: Endocrinology. 2007 Aug;148(8):3551-3
references.pmid: 17639030
references.citation: BMC Evol Biol. 2005 Apr 14;5:28
references.pmid: 15831095
references.citation: Mol Cell Endocrinol. 2002 Dec 30;198(1-2):61-7
references.pmid: 12573815
references.citation: Mech Dev. 2000 Dec;99(1-2):139-42
references.pmid: 11091081
references.citation: Nat Genet. 2002 Apr;30(4):411-5
references.pmid: 11925567
references.citation: Am J Hum Genet. 1999 Jan;64(1):24-30
references.pmid: 9915939
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):950-4
references.pmid: 18199840
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17004-9
references.pmid: 17942681
references.citation: Nat Genet. 2005 Jun;37(6):630-5
references.pmid: 15864308
references.citation: Bioessays. 2003 Apr;25(4):396-400
references.pmid: 12655646
references.citation: Proc Natl Acad Sci U S A. 1974 Jul;71(7):2848-52
references.pmid: 4527913
references.citation: Syst Biol. 2006 Aug;55(4):539-52
references.pmid: 16785212
references.citation: Endocrinology. 2006 Aug;147(8):3861-9
references.pmid: 16690796
references.citation: Mol Biol Evol. 2007 Mar;24(3):784-91
references.pmid: 17182894