title: Evolution of duplicated beta-globin genes and the structural basis of hemoglobin isoform differentiation in Mus.
abstract: The functional diversification of multigene families may be strongly influenced by mechanisms of concerted evolution such as interparalog gene conversion. The beta-globin gene family of house mice (genus Mus) represents an especially promising system for evaluating the effects of gene conversion on the functional divergence of duplicated genes. Whereas the majority of mammalian species possess tandemly duplicated copies of the adult beta-globin gene that are identical in sequence, natural populations of house mice are often polymorphic for distinct two-locus haplotypes that differ in levels of functional divergence between duplicated beta-globin genes, HBB-T1 and HBB-T2. Here, we use a phylogenetic approach to unravel the complex evolutionary history of the HBB-T1 and HBB-T2 paralogs in a taxonomically diverse set of species in the genus Mus. The main objectives of this study were 1) to reconstruct the evolutionary history of the different HBB haplotypes of house mice, 2) to assess the role of recombinational exchange between HBB-T1 and HBB-T2 in promoting concerted evolution, 3) to assess the role of recombinational exchange between HBB-T1 and HBB-T2 in creating chimeric genes, and 4) to assess the structural basis of hemoglobin isoform differentiation in species that possess distinct HBB paralogs. Results of our phylogenetic survey revealed that the HBB-T1 and HBB-T2 genes in different species of Mus exhibit the full range of evolutionary outcomes with respect to levels of interparalog divergence. At one end of the spectrum, the two identical HBB paralogs on the Hbb(s) haplotype (shared by Mus domesticus, Mus musculus, and Mus spretus) represent a classic example of concerted evolution. At the other end of the spectrum, the two distinct HBB paralogs on the Hbb(d), Hbb(p), Hbb(w1), and Hbb(w2) haplotypes (shared by multiple species in the subgenus Mus) show no trace of gene conversion and are distinguished by a number of functionally important amino acid substitutions. Because the possession of distinct HBB paralogs expands the repertoire of functionally distinct hemoglobin isoforms that can be synthesized during fetal development and postnatal life, variation in the level of functional divergence between HBB-T1 and HBB-T2 may underlie important physiological variation within and among species.
authors.affiliation: School of Biological Sciences, University of Nebraska, NE, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Runck
authors.forename: Hideaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Jay F
authors.initials: JF
authors.lastname: Storz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D020131:Genes, Duplicate / Q000235:genetics*; D006454:Hemoglobins / Q000737:chemistry / Q000145:classification* / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D055544:beta-Globins / Q000737:chemistry / Q000145:classification / Q000235:genetics*
chemical_list: D006454:Hemoglobins; D020033:Protein Isoforms; D055544:beta-Globins
references.citation: Mamm Genome. 1999 Sep;10(9):879-82
references.pmid: 10441738
references.citation: Science. 1980 Sep 19;209(4463):1336-42
references.pmid: 7414319
references.citation: J Mol Evol. 1985;22(2):160-74
references.pmid: 3934395
references.citation: Mol Biol Evol. 1985 Jul;2(4):304-20
references.pmid: 3870864
references.citation: Mol Biol Evol. 1993 Jan;10(1):73-102
references.pmid: 8383794
references.citation: Mol Biol Evol. 1993 May;10(3):512-26
references.pmid: 8336541
references.citation: J Mol Biol. 1989 Jan 5;205(1):41-62
references.pmid: 2926808
references.citation: Genome Res. 2008 Jan;18(1):67-76
references.pmid: 18025268
references.citation: Mol Ecol. 2008 Dec;17(24):5349-63
references.pmid: 19121002
references.citation: Heredity (Edinb). 1989 Dec;63 ( Pt 3):299-308
references.pmid: 2613534
references.citation: Genetics. 2008 Mar;178(3):1623-38
references.pmid: 18245844
references.citation: Evolution. 2004 Sep;58(9):2064-78
references.pmid: 15521462
references.citation: J Biol Chem. 1984 Mar 25;259(6):3748-56
references.pmid: 6706976
references.citation: Biochem Genet. 1984 Apr;22(3-4):275-303
references.pmid: 6375655
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14450-5
references.pmid: 19667207
references.citation: Cell. 1977 Dec;12(4):863-71
references.pmid: 597861
references.citation: Hum Genet. 1999 Feb;104(2):117-25
references.pmid: 10190321
references.citation: Nat Rev Genet. 2007 Oct;8(10):762-75
references.pmid: 17846636
references.citation: Mol Biol Evol. 2008 Dec;25(12):2589-600
references.pmid: 18780876
references.citation: Genetics. 2007 Dec;177(4):2277-91
references.pmid: 18073432
references.citation: High Alt Med Biol. 2008 Summer;9(2):148-57
references.pmid: 18578646
references.citation: Am Sci. 1978 Jan-Feb;66(1):52-60
references.pmid: 623400
references.citation: BMC Evol Biol. 2004 Jun 28;4:18
references.pmid: 15222900
references.citation: Mamm Genome. 2008 Mar;19(3):155-62
references.pmid: 18299925
references.citation: Immunogenetics. 2007 Apr;59(4):261-71
references.pmid: 17345114
references.citation: Mol Biol Evol. 2008 Mar;25(3):591-602
references.pmid: 18178968
references.citation: Genetics. 1969 Nov;63(3):653-67
references.pmid: 5399253
references.citation: Mol Biol Evol. 1988 Jan;5(1):63-78
references.pmid: 2833677
references.citation: Genetics. 2001 Dec;159(4):1789-804
references.pmid: 11779815
references.citation: J Mol Evol. 1979 Jun 8;13(1):1-14
references.pmid: 458868
references.citation: J Mol Biol. 1982 May 5;157(1):105-32
references.pmid: 7108955
references.citation: Mol Biol Evol. 2007 Aug;24(8):1586-91
references.pmid: 17483113
references.citation: Science. 1972 Nov 24;178(4063):873-4
references.pmid: 5085986
references.citation: Genetics. 2008 Sep;180(1):493-505
references.pmid: 18757936
references.citation: Trends Genet. 2004 Nov;20(11):544-9
references.pmid: 15475113
references.citation: Heredity (Edinb). 1989 Dec;63 ( Pt 3):289-97
references.pmid: 2575606
references.citation: Genes Genet Syst. 2006 Jun;81(3):201-9
references.pmid: 16905874
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3784-8
references.pmid: 12824418
references.citation: J Biol Chem. 1984 Mar 25;259(6):3739-47
references.pmid: 6323438
references.citation: Proc Natl Acad Sci U S A. 1990 Oct;87(19):7693-7
references.pmid: 2217202
references.citation: PLoS Genet. 2007 Mar 30;3(3):e45
references.pmid: 17397259
references.citation: Annu Rev Genet. 2005;39:121-52
references.pmid: 16285855
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12950-5
references.pmid: 18755893
references.citation: Proteins. 2002 Aug 1;48(2):227-41
references.pmid: 12112692
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1590-5
references.pmid: 18216242
references.citation: Genetics. 1995 Dec;141(4):1641-50
references.pmid: 8601501
references.citation: Genetics. 2007 Sep;177(1):481-500
references.pmid: 17660536
references.citation: Mol Biol Evol. 2009 Jul;26(7):1469-78
references.pmid: 19332641
references.citation: Bioinformatics. 2006 Jan 15;22(2):195-201
references.pmid: 16301204
references.citation: Mol Biol Evol. 1986 May;3(3):243-61
references.pmid: 3444401
references.citation: Proc Natl Acad Sci U S A. 1962 Oct 15;48:1718-24
references.pmid: 13955956
references.citation: Can J Genet Cytol. 1983 Apr;25(2):190-201
references.pmid: 6850418
references.citation: Am Zool. 1970 Feb;10(1):53-66
references.pmid: 5437297
references.citation: Genetics. 2008 Mar;178(3):1385-98
references.pmid: 18245342
references.citation: Syst Biol. 2002 Jun;51(3):410-31
references.pmid: 12079642
references.citation: Nat Genet. 1995 Aug;10(4):407-14
references.pmid: 7670490
references.citation: J Clin Invest. 1974 Jan;53(1):329-33
references.pmid: 4808645
references.citation: Proc R Soc Lond B Biol Sci. 1977 Jul 20;197(1129):485-503
references.pmid: 18741
references.citation: Ann N Y Acad Sci. 1974 Nov 29;241(0):416-33
references.pmid: 4215357
references.citation: J Mol Evol. 1996 Feb;42(2):313-20
references.pmid: 8919883
references.citation: Genetics. 2008 Sep;180(1):367-79
references.pmid: 18716337
references.citation: Proc Natl Acad Sci U S A. 1983 Apr;80(8):2290-4
references.pmid: 6300907
references.citation: C R Biol. 2002 Feb;325(2):89-97
references.pmid: 11980180
references.citation: Genetics. 2004 Mar;166(3):1553-60
references.pmid: 15082568
references.citation: J Immunogenet. 1979 Apr;6(2):99-113
references.pmid: 489997
references.citation: Nucleic Acids Res. 1997 Dec 15;25(24):4876-82
references.pmid: 9396791
references.citation: Biochemistry. 2001 Dec 25;40(51):15669-75
references.pmid: 11747442
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8793-8
references.pmid: 12857961
references.citation: Biochem Genet. 1985 Dec;23(11-12):975-86
references.pmid: 4084209
references.citation: Trends Genet. 2006 Dec;22(12):642-4
references.pmid: 17045359
references.citation: J Clin Invest. 1974 Jan;53(1):320-8
references.pmid: 4808644