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The α-Globin Gene Family of an Australian Marsupial, Macropus eugenii: The Long Evolutionary History of the θ-Globin Gene and Its Functional Status in Mammals

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Abstract

Comparative evolutionary analyses of gene families among divergent lineages can provide information on the order and timing of major gene duplication events and evolution of gene function. Here we investigate the evolutionary history of the α-globin gene family in mammals by isolating and characterizing α-like globin genes from an Australian marsupial, the tammar wallaby, Macropus eugenii. Sequence and phylogenetic analyses indicate that the tammar α-globin family consists of at least four genes including a single adult-expressed gene (α), two embryonic/neonatally expressed genes (ζ and ζ′), and θ-globin, each orthologous to the respective α-, ζ-, and θ-globin genes of eutherian mammals. The results suggest that the θ-globin lineage arose by duplication of an ancestral adult α-globin gene and had already evolved an unusual promoter region, atypical of all known α-globin gene promoters, prior to the divergence of the marsupial and eutherian lineages. Evolutionary analyses, using a maximum likelihood approach, indicate that θ-globin, has evolved under strong selective constraints in both marsupials and the lineage leading to human θ-globin, suggesting a long-term functional status. Overall, our results indicate that at least a four-gene cluster consisting of three α-like and one β-like globin genes linked in the order 5′–ζ–α–θ–ω–3′ existed in the common ancestor of marsupials and eutherians. However, results are inconclusive as to whether the two tammar ζ-globin genes arose by duplication prior to the radiation of the marsupial and eutherian lineages, with maintenance of exon sequences by gene conversion, or more recently within marsupials.

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References

  • M Albitar A Care C Peschle SA Liebhaber (1992) ArticleTitleDevelopmental switching of messenger RNA expression from the human alpha-globin cluster: fetal/adult pattern of theta-globin gene expression Blood 80 1586 Occurrence Handle1:CAS:528:DyaK38XmtlSrtr4%3D Occurrence Handle1520882

    CAS  PubMed  Google Scholar 

  • M Albitar C Peschle SA Liebhaber (1989) ArticleTitleTheta, zeta, and epsilon globin messenger RNAs are expressed in adults Blood 74 629–637 Occurrence Handle1:CAS:528:DyaL1MXlsVOkt7w%3D Occurrence Handle2752137

    CAS  PubMed  Google Scholar 

  • JM Beard EOP Thompson (1971) ArticleTitleStudies on marsupial proteins. V. Amino acid sequence of the α-chain of hemoglobin from the grey kangaroo Macropus giganteus Aust J Biol Sci 24 765–786 Occurrence Handle1:CAS:528:DyaE3MXkvFClsbs%3D Occurrence Handle5119242

    CAS  PubMed  Google Scholar 

  • JF Cheng L Raid RC Hardison (1986) ArticleTitleIsolation and nucleotide sequence of the rabbit globin gene cluster psi zeta-alpha 1-psi alpha. Absence of a pair of alpha-globin genes evolving in concert J Biol Chem 261 839–848 Occurrence Handle1:CAS:528:DyaL28Xht1Cjur8%3D Occurrence Handle3001084

    CAS  PubMed  Google Scholar 

  • JA Chiorini S Miyamoto SJ Harkin B Safer (1999) ArticleTitleGenomic cloning and characterization of the human eukaryotic initiation factor-2beta promoter J Biol Chem 274 4195–4201 Occurrence Handle1:CAS:528:DyaK1MXhslagsr4%3D Occurrence Handle9933616

    CAS  PubMed  Google Scholar 

  • JB Clegg (1987) ArticleTitleCan the product of the theta gene be a real globin? Nature 329 465–466 Occurrence Handle1:CAS:528:DyaL1cXmvF2jsQ%3D%3D Occurrence Handle3657962

    CAS  PubMed  Google Scholar 

  • J Czelusniak M Goodman D Hewett-Emmett ML Weiss PJ Venta RE Tashian (1982) ArticleTitlePhylogenetic origins and adaptive evolution of avian and mammalian hemoglobin genes Nature 298 297–300 Occurrence Handle1:CAS:528:DyaL38XlsFyhs7w%3D Occurrence Handle6178039

    CAS  PubMed  Google Scholar 

  • AA Leo ParticleDe D Wheeler C Lefevre J-F Cheng R Hope J Kuliwaba KR Nicholas M Westerman JAM Graves (2005) ArticleTitleSequencing and mapping hemoglobin gene clusters in the Australian model dasyurid marsupial Sminthopsis macroura Cytogenet Genome Res 108 333–341 Occurrence Handle15627754

    PubMed  Google Scholar 

  • BJ Efiok JA Chiorini B Safer (1994) ArticleTitleA key transcription factor for eukaryotic initiation factor-2 alpha is strongly homologous to developmental transcription factors and may link metabolic genes to cellular growth and development J Biol Chem 269 18921–18930 Occurrence Handle1:CAS:528:DyaK2cXlvFOnur0%3D Occurrence Handle8034649

    CAS  PubMed  Google Scholar 

  • A Efstratiadis JW Posakony T Maniatis RM Lawn C O’Connell RA Spritz JK DeReil BG Forget SM Weissman JL Slightom AE Blechl O Smithies FE Baralle CC Shoulders NJ Proudfoot (1980) ArticleTitleThe structure and evolution of the human β-globin gene family Cell 21 653–668 Occurrence Handle10.1016/0092-8674(80)90429-8 Occurrence Handle1:CAS:528:DyaL3cXmtFylu74%3D Occurrence Handle6985477

    Article  CAS  PubMed  Google Scholar 

  • YJ Fei S Fujita TH Huisman (1988) ArticleTitleTwo different theta globin gene deletions observed among black newborn babies Br J Haematol 68 249–253 Occurrence Handle1:CAS:528:DyaL1cXhs1anur4%3D Occurrence Handle3348979

    CAS  PubMed  Google Scholar 

  • J Felsenstein (1985) ArticleTitleConfidence limits on phylogenies: an approach using the bootstrap Evolution 39 783–791

    Google Scholar 

  • J Flint AM Taylor JB Clegg (1988) ArticleTitleStructure and evolution of the horse zeta globin locus J Mol Biol 199 427–437 Occurrence Handle1:CAS:528:DyaL1cXksV2gtb8%3D Occurrence Handle3351936

    CAS  PubMed  Google Scholar 

  • J Flint C Tufarelli J Peden K Clark RJ Daniels R Hardison W Miller S Philipsen KG Tan-Un T McMorrow J Frampton BP Alter AM Frischauf DR Higgs (2001) ArticleTitleComparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the alpha globin cluster Hum Mol Genet 10 371–382 Occurrence Handle10.1093/hmg/10.4.371 Occurrence Handle1:CAS:528:DC%2BD3MXhsVygtr0%3D Occurrence Handle11157800

    Article  CAS  PubMed  Google Scholar 

  • M Goodman BF Koop J Czelusnia ML Weiss JL Slightom (1984) ArticleTitleThe η-globin gene. Its long evolutionary history in the β-globin gene family of mammals J Mol Biol 180 803–823 Occurrence Handle10.1016/0022-2836(84)90258-4 Occurrence Handle1:CAS:528:DyaL2MXht1Kms7k%3D Occurrence Handle6527390

    Article  CAS  PubMed  Google Scholar 

  • RC Hardison (1998) ArticleTitleHemoglobins from bacteria to man: evolution of different patterns of gene expression J Exp Biol 201 1099–1117 Occurrence Handle1:CAS:528:DyaK1cXjvVOhsbg%3D Occurrence Handle9510523

    CAS  PubMed  Google Scholar 

  • RAB Holland AA Gooley (1997) ArticleTitleCharacterization of the embryonic globin chains of the marsupial tammar wallaby, Macropus eugenii Eur J Biochem 248 864–871 Occurrence Handle10.1111/j.1432-1033.1997.00864.x Occurrence Handle1:CAS:528:DyaK2sXmvFKhtLc%3D Occurrence Handle9342240

    Article  CAS  PubMed  Google Scholar 

  • RAB Holland AF Rimes A Comis CH Tyndale-Biscoe (1988) ArticleTitleOxygen carriage and carbonic anhydrase activity in the blood of a marsupial, the tammar wallaby (Macropus eugenii), during early development Respir Physiol 73 69–86 Occurrence Handle10.1016/0034-5687(88)90128-4 Occurrence Handle1:STN:280:BiaD3Mfms1Q%3D Occurrence Handle3140330

    Article  CAS  PubMed  Google Scholar 

  • RM Hope SJB Cooper BJ Wainwright (1990) ArticleTitleGlobin macromolecular sequences in marsupials and monotremes Aust J Zool 37 289–313 Occurrence Handle1:CAS:528:DyaK3cXksFCgurc%3D

    CAS  Google Scholar 

  • SL Hsu J Marks JP Shaw M Tarn DR Higgs CC Shen CK Shen (1988) ArticleTitleStructure and expression of the human theta 1 globin gene Nature 331 94–96 Occurrence Handle1:CAS:528:DyaL1cXktVWlsrc%3D Occurrence Handle3422341

    CAS  PubMed  Google Scholar 

  • JP Huelsenbeck F Ronquist (2001) ArticleTitleMRBAYES: Bayesian inference of phylogeny Bioinformatics 17 754–755 Occurrence Handle10.1093/bioinformatics/17.8.754 Occurrence Handle1:STN:280:DC%2BD3MvotV2isw%3D%3D Occurrence Handle11524383

    Article  CAS  PubMed  Google Scholar 

  • J Lauer C-KJ Shen T Maniatis (1980) ArticleTitleThe chromosomal arrangement of human α-like globin genes: sequence homology and α-globin gene deletions Cell 267 119–130

    Google Scholar 

  • S Leung E Whitelaw NJ Proudfoot (1989) ArticleTitleTranscriptional and translational analysis of the human θ-globin gene Nucleic Acids Res 17 8283–8300 Occurrence Handle1:CAS:528:DyaK3cXhvVKn Occurrence Handle2813063

    CAS  PubMed  Google Scholar 

  • SA Liebhaber M Goossens YW Kan (1981) ArticleTitleHomology and concerted evolution at the αl and α2 loci of human α-globin Nature 290 26–29 Occurrence Handle1:CAS:528:DyaL3MXkt1ajsro%3D Occurrence Handle7010180

    CAS  PubMed  Google Scholar 

  • O Madsen M Scally CJ Douady DJ Kao RW De Bry R Adkins HM Amrine MJ Stanhope WW de Jong MS Springer (2001) ArticleTitleParallel adaptive radiations in two major clades of placental mammals Nature 409 610–614 Occurrence Handle1:CAS:528:DC%2BD3MXhtVygur4%3D Occurrence Handle11214318

    CAS  PubMed  Google Scholar 

  • J Marks J-P Shaw C-KJ Shen (1986) ArticleTitleSequence organization and genomic complexity of primate θ1 globin gene, a novel α-globin-like gene Nature 321 785–788 Occurrence Handle1:CAS:528:DyaL28XkvFahu7g%3D Occurrence Handle3012370

    CAS  PubMed  Google Scholar 

  • WJ Murphy E Eizirik WE Johnson YP Zhang OA Ryder SJ O’Brien (2001) ArticleTitleMolecular phylogenetics and the origins of placental mammals Nature 409 614–618 Occurrence Handle10.1038/35054550 Occurrence Handle1:CAS:528:DC%2BD3MXhtVylt7Y%3D Occurrence Handle11214319

    Article  CAS  PubMed  Google Scholar 

  • M Nei T Gojobori (1986) ArticleTitleSimple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions Mol Biol Evol 3 418–426 Occurrence Handle1:CAS:528:DyaL28Xmt1aisbs%3D Occurrence Handle3444411

    CAS  PubMed  Google Scholar 

  • SH Orkin (1978) ArticleTitleThe duplicated human α globin genes lie close together in cellular DNA Proc Natl Acad Sci USA 75 5950–5954 Occurrence Handle1:CAS:528:DyaE1MXhtVWjsL0%3D Occurrence Handle282616

    CAS  PubMed  Google Scholar 

  • D Posada KA Crandall (1998) ArticleTitleModeltest: testing the model of DNA substitution Bioinformatics 14 817–818 Occurrence Handle10.1093/bioinformatics/14.9.817 Occurrence Handle1:CAS:528:DyaK1MXktlCltw%3D%3D Occurrence Handle9918953

    Article  CAS  PubMed  Google Scholar 

  • NJ Proudfoot A Gil T Maniatis (1982) ArticleTitleThe structure of the human zeta-globin gene and a closely linked, nearly identical pseudogene Cell 31 553–563 Occurrence Handle1:CAS:528:DyaL3sXosVejtQ%3D%3D Occurrence Handle6297773

    CAS  PubMed  Google Scholar 

  • NJ Proudfoot T Maniatis (1980) ArticleTitleThe structure of a human α-globin pseudogene and its relationship to α-globin gene duplication Cell 21 537–544 Occurrence Handle1:CAS:528:DyaL3cXmtFKku7o%3D Occurrence Handle7407925

    CAS  PubMed  Google Scholar 

  • F Rodríguez JF Oliver A Marin JR Medina (1990) ArticleTitleThe general stochastic model of nucleotide substitutions J Theor Biol 142 485–501 Occurrence Handle2338834

    PubMed  Google Scholar 

  • J Rozas R Rozas (1997) ArticleTitleDnaSP version 2.0: a novel software package for extensive molecular population genetics analysis Comput Appl Biosci 13 307–311 Occurrence Handle1:CAS:528:DyaK2sXksVGntb8%3D Occurrence Handle9183537

    CAS  PubMed  Google Scholar 

  • H Satoh N Inokuchi Y Nagae T Okazaki (1999) ArticleTitleMolecular cloning and characterization of two sets of α-θ genes in the rat α-like globin gene cluster Gene 230 91–99 Occurrence Handle1:CAS:528:DyaK1MXivFyrsLo%3D Occurrence Handle10196478

    CAS  PubMed  Google Scholar 

  • I Sawada CW Schmid (1986) ArticleTitlePrimate evolution of the alpha-globin gene cluster and its Alu-like repeats J Mol Biol 192 693–709 Occurrence Handle1:CAS:528:DyaL2sXhtlaktb8%3D Occurrence Handle3586010

    CAS  PubMed  Google Scholar 

  • JP Shaw J Marks CK Shen (1987) ArticleTitleEvidence that the recently discovered thetal-globin gene is functional in higher primates Nature 326 717–720 Occurrence Handle1:CAS:528:DyaL2sXkslWrurw%3D Occurrence Handle3561513

    CAS  PubMed  Google Scholar 

  • DL Swofford (2002) PAUP*. Phylogenetic analysis using parsimony (*and Other Methods). Version 4.0b10 Sinauert Sunderland, MA

    Google Scholar 

  • B Wainwright RM Hope (1985) ArticleTitleCloning and chromosomal location of the α- and β-globin genes from a marsupial Proc Natl Acad Sci USA 82 8105–8108 Occurrence Handle1:CAS:528:DyaL28Xmtlahsw%3D%3D Occurrence Handle3865220

    CAS  PubMed  Google Scholar 

  • D Wheeler RM Hope SJB Cooper G Dolman GC Webb CD Bottema AA Gooley M Goodman RAB Holland (2001) ArticleTitleAn orphaned mammalian β-globin gene of ancient evolutionary origin Proc Natl Acad Sci USA 98 1101–1106 Occurrence Handle10.1073/pnas.98.3.1101 Occurrence Handle1:CAS:528:DC%2BD3MXht1Smsbg%3D Occurrence Handle11158601

    Article  CAS  PubMed  Google Scholar 

  • D Wheeler RM Hope SJB Cooper AA Gooley RAB Holland (2004) ArticleTitleLinkage of the β-like ω-globin gene to like globin genes in an Australian marsupial supports the chromosome duplication model for separation of globin gene clusters J Mol Evol 58 642–652 Occurrence Handle1:CAS:528:DC%2BD2cXkvVOhsr4%3D Occurrence Handle15461421

    CAS  PubMed  Google Scholar 

  • Z Yang (1996) ArticleTitleAmong-site rate variation and its impact on phylogenetic analyses Trends Ecol Evol 11 367–372 Occurrence Handle10.1016/0169-5347(96)10041-0

    Article  Google Scholar 

  • Z Yang (1997) Phylogenetic analysis by maximum likelihood (PAML). Version 1.3. University of California Berkeley

    Google Scholar 

  • Z Yang (1998) ArticleTitleLikelihood ratio tests for detecting positive selection and application to primate lysozyme evolution Mol Biol Evol 15 568–573 Occurrence Handle1:CAS:528:DyaK1cXislensL4%3D Occurrence Handle9580986

    CAS  PubMed  Google Scholar 

  • Z Zhang SJ Gurr (2000) ArticleTitleWalking into the unknown: a ‘step down’ PCR-based technique leading to the direct sequence analysis of flanking genomic DNA Gene 253 145–150 Occurrence Handle1:CAS:528:DC%2BD3cXlsFSlt7g%3D Occurrence Handle10940551

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank K. Gill for information on unpublished data and J. Armstrong for technical assistance. We thank A. De Leo and J. Graves for providing a copy of their paper on globin genes in S. macroura, recently accepted for publication in Cytogenetic and Genome Research. A grant from the Australian Research Council to R.A.B.H., and R.M.H. supported this research.

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Author notes

  1. David Wheeler

    Present address: Australian and New Zealand Council for the Care of Animals in Teaching and Research, University of Adelaide, South Australia, 5005, Australia

  2. Gaynor Dolman

    Present address: Department of Zoology and Entomology, University of Queensland, St. Lucia, Queensland, 4072, Australia

Authors and Affiliations

  1. Evolutionary Biology Unit, South Australian Museum, Adelaide, South Australia, 5005, Australia

    Steven J.B. Cooper, Gaynor Dolman & Kathleen M. Saint

  2. School of Molecular and Biomedical Science, The University of Adelaide, South Australia, 5005, Australia

    David Wheeler & Rory M. Hope

  3. Centre for Evolutionary Biology and Biodiversity, The University of Adelaide, South Australia, 5005, Australia

    Steven J.B. Cooper, David Wheeler & Rory M. Hope

  4. Proteome Systems Ltd., North Ryde, New South Wales, 1670, Australia

    Andrew A. Gooley

  5. Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, New South Wales, 2052, Australia

    Robert A.B. Holland

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  1. Steven J.B. Cooper
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Correspondence to Steven J.B. Cooper.

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Cooper, S.J., Wheeler, D., Hope, R.M. et al. The α-Globin Gene Family of an Australian Marsupial, Macropus eugenii: The Long Evolutionary History of the θ-Globin Gene and Its Functional Status in Mammals. J Mol Evol 60, 653–664 (2005). https://doi.org/10.1007/s00239-004-0247-9

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