title: New genes originated via multiple recombinational pathways in the beta-globin gene family of rodents.
abstract: Species differences in the size or membership composition of multigene families can be attributed to lineage-specific additions of new genes via duplication, losses of genes via deletion or inactivation, and the creation of chimeric genes via domain shuffling or gene fusion. In principle, it should be possible to infer the recombinational pathways responsible for each of these different types of genomic change by conducting detailed comparative analyses of genomic sequence data. Here, we report an attempt to unravel the complex evolutionary history of the beta-globin gene family in a taxonomically diverse set of rodent species. The main objectives were: 1) to characterize the genomic structure of the beta-globin gene cluster of rodents; 2) to assign orthologous and paralogous relationships among duplicate copies of beta-like globin genes; and 3) to infer the specific recombinational pathways responsible for gene duplications, gene deletions, and the creation of chimeric fusion genes. Results of our comparative genomic analyses revealed that variation in gene family size among rodent species is mainly attributable to the differential gain and loss of later expressed beta-globin genes via unequal crossing-over. However, two distinct recombinational mechanisms were implicated in the creation of chimeric fusion genes. In muroid rodents, a chimeric gamma/epsilon fusion gene was created by unequal crossing-over between the embryonic epsilon- and gamma-globin genes. Interestingly, this gamma/epsilon fusion gene was generated in the same fashion as the "anti-Lepore" 5'-delta-(beta/delta)-beta-3' duplication mutant in humans (the reciprocal exchange product of the pathological hemoglobin Lepore deletion mutant). By contrast, in the house mouse, Mus musculus, a chimeric beta/delta fusion pseudogene was created by a beta-globin --> delta-globin gene conversion event. Although the gamma/epsilon and beta/delta fusion genes share a similar chimeric gene structure, they originated via completely different recombinational pathways.
authors.affiliation: School of Biological Sciences, University of Nebraska, USA.
authors.forename: Federico G
authors.initials: FG
authors.lastname: Hoffmann
authors.forename: Juan C
authors.initials: JC
authors.lastname: Opazo
authors.forename: Jay F
authors.initials: JF
authors.lastname: Storz
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D051379:Mice; D005810:Multigene Family; D051381:Rats; D011995:Recombination, Genetic; D012377:Rodentia / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics*
chemical_list: D055544:beta-Globins
references.citation: FEMS Microbiol Lett. 1999 May 15;174(2):247-50
references.pmid: 10339815
references.citation: Mol Biol Evol. 2008 Mar;25(3):591-602
references.pmid: 18178968
references.citation: J Mol Biol. 1984 Dec 25;180(4):803-23
references.pmid: 6527390
references.citation: Science. 2001 Dec 14;294(5550):2348-51
references.pmid: 11743200
references.citation: Nucleic Acids Res. 1997 Dec 15;25(24):4876-82
references.pmid: 9396791
references.citation: Cell. 1980 Apr;19(4):959-72
references.pmid: 6155216
references.citation: Prog Nucleic Acid Res Mol Biol. 1984;31:315-462
references.pmid: 6397774
references.citation: Gene. 1989 Jun 30;79(1):139-50
references.pmid: 2777087
references.citation: Cell. 1987 Dec 24;51(6):975-85
references.pmid: 3690667
references.citation: Mol Cell Biol. 1992 Mar;12(3):1292-303
references.pmid: 1545810
references.citation: Mol Biol Evol. 1985 Nov;2(6):514-25
references.pmid: 3870874
references.citation: Nat Rev Genet. 2003 Nov;4(11):865-75
references.pmid: 14634634
references.citation: Genetics. 2008 Mar;178(3):1623-38
references.pmid: 18245844
references.citation: J Biol Chem. 1984 Mar 25;259(6):3748-56
references.pmid: 6706976
references.citation: Mol Biol Evol. 1996 Sep;13(7):1012-22
references.pmid: 8752008
references.citation: PLoS Genet. 2007 Nov;3(11):e197
references.pmid: 17997610
references.citation: Gene. 1997 Dec 31;205(1-2):73-94
references.pmid: 9461381
references.citation: Mol Biol Evol. 1984 Jul;1(4):302-16
references.pmid: 6599969
references.citation: Genome Res. 2005 Jan;15(1):184-94
references.pmid: 15590941
references.citation: BMC Evol Biol. 2004 Jun 28;4:18
references.pmid: 15222900
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3518-24
references.pmid: 12824357
references.citation: J Biol Chem. 1991 Apr 25;266(12):7469-80
references.pmid: 2019578
references.citation: Nat Rev Genet. 2006 Feb;7(2):85-97
references.pmid: 16418744
references.citation: PLoS One. 2006 Dec 20;1:e85
references.pmid: 17183716
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):10950-5
references.pmid: 17573529
references.citation: Syst Biol. 2004 Aug;53(4):533-53
references.pmid: 15371245
references.citation: J Theor Biol. 1990 Feb 22;142(4):485-501
references.pmid: 2338834
references.citation: Mol Biol Evol. 2008 Sep;25(9):1795-808
references.pmid: 18453548
references.citation: J Biol Chem. 1984 Mar 25;259(6):3739-47
references.pmid: 6323438
references.citation: Mol Phylogenet Evol. 2005 Apr;35(1):225-34
references.pmid: 15737593
references.citation: Mol Biol Evol. 1985 Jul;2(4):304-20
references.pmid: 3870864
references.citation: Proc Natl Acad Sci U S A. 1990 Oct;87(19):7693-7
references.pmid: 2217202
references.citation: Proc Natl Acad Sci U S A. 1984 Nov;81(21):6589-93
references.pmid: 6593719
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7122-7
references.pmid: 17438280
references.citation: PLoS Genet. 2007 Mar 30;3(3):e45
references.pmid: 17397259
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14560-5
references.pmid: 11121057
references.citation: Genes Genet Syst. 2006 Oct;81(5):367-71
references.pmid: 17159299
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12950-5
references.pmid: 18755893
references.citation: J Mol Evol. 1989 Mar;28(3):175-84
references.pmid: 2494347
references.citation: Genetics. 2007 Sep;177(1):481-500
references.pmid: 17660536
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1590-5
references.pmid: 18216242
references.citation: Mol Biol Evol. 1984 Sep;1(5):390-410
references.pmid: 6599973
references.citation: Hum Mol Genet. 2006 Apr 1;15(7):1099-111
references.pmid: 16501000
references.citation: Genetics. 2007 Nov;177(3):1941-9
references.pmid: 17947411
references.citation: J Mol Biol. 1989 Jan 5;205(1):15-40
references.pmid: 2486295
references.citation: Mol Biol Evol. 1986 May;3(3):243-61
references.pmid: 3444401
references.citation: J Exp Biol. 1998 Apr;201(Pt 8):1099-117
references.pmid: 9510523
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4701-6
references.pmid: 10758160
references.citation: Mol Biol Evol. 1988 Mar;5(2):134-40
references.pmid: 3367782
references.citation: Bioinformatics. 2003 Aug 12;19(12):1572-4
references.pmid: 12912839
references.citation: Hum Mol Genet. 2002 Feb 1;11(3):207-15
references.pmid: 11823440
references.citation: J Mol Biol. 1982 Apr 15;156(3):487-503
references.pmid: 6214636
references.citation: J Biol Chem. 1989 Jan 5;264(1):68-79
references.pmid: 2491855
references.citation: J Mol Biol. 1997 Apr 25;268(1):78-94
references.pmid: 9149143
references.citation: Mol Biol Evol. 1993 Jan;10(1):73-102
references.pmid: 8383794
references.citation: PLoS Genet. 2005 Dec;1(6):e49
references.pmid: 16444292
references.citation: Genome Res. 2000 Apr;10(4):577-86
references.pmid: 10779500
references.citation: Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R57-64
references.pmid: 14764619
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):8921-7
references.pmid: 16709669
references.citation: Genetics. 1991 May;128(1):143-61
references.pmid: 2060774
references.citation: Mol Biol Evol. 1990 Sep;7(5):407-22
references.pmid: 2263193
references.citation: Cold Spring Harb Symp Quant Biol. 1987;52:875-90
references.pmid: 3454296
references.citation: Proc Natl Acad Sci U S A. 1988 Jun;85(11):3893-7
references.pmid: 3375246
references.citation: J Mol Biol. 1989 Jan 5;205(1):41-62
references.pmid: 2926808