Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Nov;81(21):6589–6593. doi: 10.1073/pnas.81.21.6589

Triplication of a four-gene set during evolution of the goat beta-globin locus produced three genes now expressed differentially during development.

T M Townes, M C Fitzgerald, J B Lingrel
PMCID: PMC391975  PMID: 6593719

Abstract

Distinct hemoglobins are synthesized in goats at different stages of development, similar to humans. Embryonic hemoglobins (zeta 2 epsilon 2 and alpha 2 epsilon 2) are synthesized initially and are followed sequentially by fetal (alpha 2 beta F2), preadult (alpha 2 beta C2), and adult (alpha 2 beta A2) hemoglobins. To help understand the basis of these switches, the genes of the beta-globin locus have been cloned and their linkage arrangement has been determined by the isolation of lambda phage carrying overlapping inserts of genomic goat DNA. The locus extends over 120 kilobase pairs and consists of 12 genes arranged in the following order: epsilon I-epsilon II-psi beta X-beta C-epsilon III-epsilon IV-psi beta Z-beta A-epsilon V-epsilon VI-psi beta Y-beta F. Comparison of the nucleotide sequence of the 12 genes shows that the locus is organized into three homologous four-gene sets that presumably evolved by the triplication of an ancestral set of four genes (epsilon-epsilon-psi beta-beta). Interestingly, the three genes (beta C, beta A, and beta F) located at the ends of the four-gene sets are expressed at different stages of development. Therefore, the goat beta F-, beta C-, and beta A-globin genes appear to have evolved by a mechanism that includes the triplication of 40-50 kilobase pairs of DNA and the recruitment of newly formed genes for expression in fetal, preadult, and adult life.

Full text

PDF
6590

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baralle F. E., Shoulders C. C., Proudfoot N. J. The primary structure of the human epsilon-globin gene. Cell. 1980 Oct;21(3):621–626. doi: 10.1016/0092-8674(80)90425-0. [DOI] [PubMed] [Google Scholar]
  2. Benoist C., O'Hare K., Breathnach R., Chambon P. The ovalbumin gene-sequence of putative control regions. Nucleic Acids Res. 1980 Jan 11;8(1):127–142. doi: 10.1093/nar/8.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  4. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  5. Cleary M. L., Haynes J. R., Schon E. A., Lingrel J. B. Identification by nucleotide sequence analysis of a goat pseudoglobin gene. Nucleic Acids Res. 1980 Oct 24;8(20):4791–4802. doi: 10.1093/nar/8.20.4791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cleary M. L., Schon E. A., Lingrel J. B. Two related pseudogenes are the result of a gene duplication in the goat beta-globin locus. Cell. 1981 Oct;26(2 Pt 2):181–190. doi: 10.1016/0092-8674(81)90301-9. [DOI] [PubMed] [Google Scholar]
  7. Czelusniak J., Goodman M., Hewett-Emmett D., Weiss M. L., Venta P. J., Tashian R. E. Phylogenetic origins and adaptive evolution of avian and mammalian haemoglobin genes. Nature. 1982 Jul 15;298(5871):297–300. doi: 10.1038/298297a0. [DOI] [PubMed] [Google Scholar]
  8. Dierks P., van Ooyen A., Cochran M. D., Dobkin C., Reiser J., Weissmann C. Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit beta-globin gene in mouse 3T6 cells. Cell. 1983 Mar;32(3):695–706. doi: 10.1016/0092-8674(83)90055-7. [DOI] [PubMed] [Google Scholar]
  9. Efstratiadis A., Posakony J. W., Maniatis T., Lawn R. M., O'Connell C., Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M., Slightom J. L. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653–668. doi: 10.1016/0092-8674(80)90429-8. [DOI] [PubMed] [Google Scholar]
  10. Fritsch E. F., Lawn R. M., Maniatis T. Molecular cloning and characterization of the human beta-like globin gene cluster. Cell. 1980 Apr;19(4):959–972. doi: 10.1016/0092-8674(80)90087-2. [DOI] [PubMed] [Google Scholar]
  11. Hansen J. N., Konkel D. A., Leder P. The sequence of a mouse embryonic beta-globin gene. Evolution of the gene and its signal region. J Biol Chem. 1982 Jan 25;257(2):1048–1052. [PubMed] [Google Scholar]
  12. Hardies S. C., Edgell M. H., Hutchison C. A., 3rd Evolution of the mammalian beta-globin gene cluster. J Biol Chem. 1984 Mar 25;259(6):3748–3756. [PubMed] [Google Scholar]
  13. Hardison R. C., Butler E. T., 3rd, Lacy E., Maniatis T., Rosenthal N., Efstratiadis A. The structure and transcription of four linked rabbit beta-like globin genes. Cell. 1979 Dec;18(4):1285–1297. doi: 10.1016/0092-8674(79)90239-3. [DOI] [PubMed] [Google Scholar]
  14. Hardison R. C. The nucleotide sequence of rabbit embryonic globin gene beta 3. J Biol Chem. 1981 Nov 25;256(22):11780–11786. [PubMed] [Google Scholar]
  15. Hardison R. C. The nucleotide sequence of the rabbit embryonic globin gene beta 4. J Biol Chem. 1983 Jul 25;258(14):8739–8744. [PubMed] [Google Scholar]
  16. Haynes J. R., Rosteck P., Jr, Lingrel J. B. Unusual sequence homology at the 5-ends of the developmentally regulated beta A-, beta C-, and gamma-globin genes of the goat. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7127–7131. doi: 10.1073/pnas.77.12.7127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Haynes J. R., Rosteck P., Jr, Schon E. A., Gallagher P. M., Burks D. J., Smith K., Lingrel J. B. The isolation of the beta A-, beta C-, and gamma-globin genes and a presumptive embryonic globin gene from a goat DNA recombinant library. J Biol Chem. 1980 Jul 10;255(13):6355–6367. [PubMed] [Google Scholar]
  18. Huisman T. H., Adams H. R., Dimmock M. O., Edwards W. E., Wilson J. B. The structure of goat hemoglobins. I. Structural studies of the beta chains of the hemoglobins of normal and anemic goats. J Biol Chem. 1967 May 25;242(10):2534–2541. [PubMed] [Google Scholar]
  19. Huisman T. H., Lewis J. P., Blunt M. H., Adams H. R., Miller A., Dozy A. M., Boyd E. M. Hemoglobin C in newborn sheep and goats: a possible explanation for its function and biosynthesis. Pediatr Res. 1969 May;3(3):189–198. doi: 10.1203/00006450-196905000-00001. [DOI] [PubMed] [Google Scholar]
  20. Huisman T. H. The in vivo production of hemoglobin C in ruminants. Ann N Y Acad Sci. 1974 Nov 29;241(0):549–555. doi: 10.1111/j.1749-6632.1974.tb21911.x. [DOI] [PubMed] [Google Scholar]
  21. Jahn C. L., Hutchison C. A., 3rd, Phillips S. J., Weaver S., Haigwood N. L., Voliva C. F., Edgell M. H. DNA sequence organization of the beta-globin complex in the BALB/c mouse. Cell. 1980 Aug;21(1):159–168. doi: 10.1016/0092-8674(80)90123-3. [DOI] [PubMed] [Google Scholar]
  22. Kitchen H., Brett I. Embryonic and fetal hemoglobin in animals. Ann N Y Acad Sci. 1974 Nov 29;241(0):653–671. doi: 10.1111/j.1749-6632.1974.tb21921.x. [DOI] [PubMed] [Google Scholar]
  23. Kretschmer P. J., Coon H. C., Davis A., Harrison M., Nienhuis A. W. Hemoglobin switching in sheep. Isolation of the fetal gamma-globin gene and demonstration that the fetal gamma- and adult beta A-globin genes lie within eight kilobase segments of homologous DNA. J Biol Chem. 1981 Feb 25;256(4):1975–1982. [PubMed] [Google Scholar]
  24. Lacy E., Hardison R. C., Quon D., Maniatis T. The linkage arrangement of four rabbit beta-like globin genes. Cell. 1979 Dec;18(4):1273–1283. doi: 10.1016/0092-8674(79)90238-1. [DOI] [PubMed] [Google Scholar]
  25. Lacy E., Hardison R. C., Quon D., Maniatis T. The linkage arrangement of four rabbit beta-like globin genes. Cell. 1979 Dec;18(4):1273–1283. doi: 10.1016/0092-8674(79)90238-1. [DOI] [PubMed] [Google Scholar]
  26. Lacy E., Maniatis T. The nucleotide sequence of a rabbit beta-globin pseudogene. Cell. 1980 Sep;21(2):545–553. doi: 10.1016/0092-8674(80)90492-4. [DOI] [PubMed] [Google Scholar]
  27. Lingrel J. B., Townes T. M., Shapiro S. G., Spence S. E., Liberator P. A., Wernke S. M. Organization, structure, and expression of the goat globin genes. Prog Clin Biol Res. 1983;134:131–139. [PubMed] [Google Scholar]
  28. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  29. Robbins J., Rosteck P., Jr, Haynes J. R., Freyer G., Cleary M. L., Kalter H. D., Smith K., Lingrel J. B. The isolation and partial characterization of recombinant DNA containing genomic globin sequences from the goat. J Biol Chem. 1979 Jul 10;254(13):6187–6195. [PubMed] [Google Scholar]
  30. Schon E. A., Cleary M. L., Haynes J. R., Lingrel J. B. Structure and evolution of goat gamma-, beta C- and beta A-globin genes: three developmentally regulated genes contain inserted elements. Cell. 1981 Dec;27(2 Pt 1):359–369. doi: 10.1016/0092-8674(81)90419-0. [DOI] [PubMed] [Google Scholar]
  31. Shapiro S. G., Schon E. A., Townes T. M., Lingrel J. B. Sequence and linkage of the goat epsilon I and epsilon II beta-globin genes. J Mol Biol. 1983 Sep 5;169(1):31–52. doi: 10.1016/s0022-2836(83)80174-0. [DOI] [PubMed] [Google Scholar]
  32. Thurmon T. F., Boyer S. H., Crosby E. F., Shepard M. K., Noyes A. N., Stohlman F., Jr Hemoglobin switching in nonanemic sheep. 3. Evidence for presumptive identity between the A--C factor and erythropoietin. Blood. 1970 Nov;36(5):598–606. [PubMed] [Google Scholar]
  33. Townes T. M., Shapiro S. G., Wernke S. M., Lingrel J. B. Duplication of a four-gene set during the evolution of the goat beta-globin locus produced genes now expressed differentially in development. J Biol Chem. 1984 Feb 10;259(3):1896–1900. [PubMed] [Google Scholar]
  34. Tucker E. M. Genetic variation in the sheep red blood cell. Biol Rev Camb Philos Soc. 1971 Aug;46(3):341–386. doi: 10.1111/j.1469-185x.1971.tb01049.x. [DOI] [PubMed] [Google Scholar]
  35. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  36. Weatherall D. J., Clegg J. B. Recent developments in the molecular genetics of human hemoglobin. Cell. 1979 Mar;16(3):467–479. doi: 10.1016/0092-8674(79)90022-9. [DOI] [PubMed] [Google Scholar]
  37. Wilson J. B., Adams H. R., Huisman T. H. The heterogeneity of the fetal hemoglobin of the goat. Biochim Biophys Acta. 1969 Jul 1;181(2):367–372. doi: 10.1016/0005-2795(69)90269-4. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES