Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1986 Feb 25;14(4):1903–1911. doi: 10.1093/nar/14.4.1903

A previously undetected pseudogene in the human alpha globin gene cluster.

R C Hardison, I Sawada, J F Cheng, C K Shen, C W Schmid
PMCID: PMC339581  PMID: 3952001

Abstract

The sequence of the DNA between two pseudogenes in the human alpha-like globin gene cluster has been determined. Comparison of this sequence with sequences from other alpha-like globin gene clusters revealed another pseudogene, psi alpha 2, between the previously recognized pseudogenes zeta 1 and psi alpha 1. Therefore, the human alpha-like globin gene family is organized 5'-zeta 2-zeta 1-psi alpha 2-psi alpha 1-alpha 2-alpha 1-3'. The new pseudogene psi alpha 2 is very close to zeta 1, beginning only 65 base pairs 3' to the polyadenylation site of zeta 1. The first exon and the first intron of psi alpha 2 are interrupted by large inserts which are flanked by short (6 to 8 base pairs) direct repeats. The pseudogene psi alpha 2 lacks a promoter for transcription by RNA polymerase II, the first exon is highly divergent, one splice site is mutated, and five different frameshift mutations have occurred in the coding regions. Thus psi alpha 2 cannot encode a globin polypeptide. This pseudogene was not recognized in previous hybridization analyses of the human alpha-like globin gene cluster, and our discovery of it by sequence analysis suggests that divergent copies of a large number of genes may comprise a substantial fraction of the slowly renaturing DNA of mammalian genomes.

Full text

PDF
1903

Selected References

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

  1. Burr H. E., Schimke R. T. Intragenomic DNA sequence homologies in the chicken and other members of the class Aves: DNA re-association under reduced stringency conditions. J Mol Evol. 1980 Aug;15(4):291–307. doi: 10.1007/BF01733136. [DOI] [PubMed] [Google Scholar]
  2. Collins F. S., Weissman S. M. The molecular genetics of human hemoglobin. Prog Nucleic Acid Res Mol Biol. 1984;31:315–462. doi: 10.1016/s0079-6603(08)60382-7. [DOI] [PubMed] [Google Scholar]
  3. Deininger P. L., Schmid C. W. A study of the evolution of repeated DNA sequences in primates and the existence of a new class of repetitive sequences in primates. J Mol Biol. 1979 Feb 5;127(4):437–460. doi: 10.1016/0022-2836(79)90231-6. [DOI] [PubMed] [Google Scholar]
  4. Fox G. M., Schmid C. W. Related single copy sequences in the human genome. Biochim Biophys Acta. 1980 Oct 17;609(3):349–363. doi: 10.1016/0005-2787(80)90109-4. [DOI] [PubMed] [Google Scholar]
  5. Hess J. F., Fox M., Schmid C., Shen C. K. Molecular evolution of the human adult alpha-globin-like gene region: insertion and deletion of Alu family repeats and non-Alu DNA sequences. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5970–5974. doi: 10.1073/pnas.80.19.5970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hess J. F., Schmid C. W., Shen C. K. A gradient of sequence divergence in the human adult alpha-globin duplication units. Science. 1984 Oct 5;226(4670):67–70. doi: 10.1126/science.6474190. [DOI] [PubMed] [Google Scholar]
  7. Hollis G. F., Hieter P. A., McBride O. W., Swan D., Leder P. Processed genes: a dispersed human immunoglobulin gene bearing evidence of RNA-type processing. Nature. 1982 Mar 25;296(5855):321–325. doi: 10.1038/296321a0. [DOI] [PubMed] [Google Scholar]
  8. Hutchison C. A., 3rd, Hardies S. C., Padgett R. W., Weaver S., Edgell M. H. The mouse globin pseudogene beta h3 is descended from a premammalian delta-globin gene. J Biol Chem. 1984 Oct 25;259(20):12881–12889. [PubMed] [Google Scholar]
  9. Ivanov I. G., Markov G. G. Heterogeneity of mouse unique deoxyribonucleic acid. FEBS Lett. 1974 Oct 15;47(2):323–326. doi: 10.1016/0014-5793(74)81039-2. [DOI] [PubMed] [Google Scholar]
  10. Lauer J., Shen C. K., Maniatis T. The chromosomal arrangement of human alpha-like globin genes: sequence homology and alpha-globin gene deletions. Cell. 1980 May;20(1):119–130. doi: 10.1016/0092-8674(80)90240-8. [DOI] [PubMed] [Google Scholar]
  11. Liebhaber S. A., Goossens M. J., Kan Y. W. Cloning and complete nucleotide sequence of human 5'-alpha-globin gene. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7054–7058. doi: 10.1073/pnas.77.12.7054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Maniatis T., Fritsch E. F., Lauer J., Lawn R. M. The molecular genetics of human hemoglobins. Annu Rev Genet. 1980;14:145–178. doi: 10.1146/annurev.ge.14.120180.001045. [DOI] [PubMed] [Google Scholar]
  13. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  14. Michelson A. M., Orkin S. H. Boundaries of gene conversion within the duplicated human alpha-globin genes. Concerted evolution by segmental recombination. J Biol Chem. 1983 Dec 25;258(24):15245–15254. [PubMed] [Google Scholar]
  15. Michelson A. M., Orkin S. H. The 3' untranslated regions of the duplicated human alpha-globin genes are unexpectedly divergent. Cell. 1980 Nov;22(2 Pt 2):371–377. doi: 10.1016/0092-8674(80)90347-5. [DOI] [PubMed] [Google Scholar]
  16. Paulson K. E., Deka N., Schmid C. W., Misra R., Schindler C. W., Rush M. G., Kadyk L., Leinwand L. A transposon-like element in human DNA. Nature. 1985 Jul 25;316(6026):359–361. doi: 10.1038/316359a0. [DOI] [PubMed] [Google Scholar]
  17. Perler F., Efstratiadis A., Lomedico P., Gilbert W., Kolodner R., Dodgson J. The evolution of genes: the chicken preproinsulin gene. Cell. 1980 Jun;20(2):555–566. doi: 10.1016/0092-8674(80)90641-8. [DOI] [PubMed] [Google Scholar]
  18. Peschle C., Mavilio F., Carè A., Migliaccio G., Migliaccio A. R., Salvo G., Samoggia P., Petti S., Guerriero R., Marinucci M. Haemoglobin switching in human embryos: asynchrony of zeta----alpha and epsilon----gamma-globin switches in primitive and definite erythropoietic lineage. Nature. 1985 Jan 17;313(5999):235–238. doi: 10.1038/313235a0. [DOI] [PubMed] [Google Scholar]
  19. Phillips S. J., Hardies S. C., Jahn C. L., Edgell M. H., Hutchison C. A., 3rd The complete nucleotide sequence of a beta-globin-like structure, beta h2, from the [Hbb]d mouse BALB/c. J Biol Chem. 1984 Jun 25;259(12):7947–7954. [PubMed] [Google Scholar]
  20. Proudfoot N. J., Gil A., Maniatis T. The structure of the human zeta-globin gene and a closely linked, nearly identical pseudogene. Cell. 1982 Dec;31(3 Pt 2):553–563. doi: 10.1016/0092-8674(82)90311-7. [DOI] [PubMed] [Google Scholar]
  21. Proudfoot N. J., Maniatis T. The structure of a human alpha-globin pseudogene and its relationship to alpha-globin gene duplication. Cell. 1980 Sep;21(2):537–544. doi: 10.1016/0092-8674(80)90491-2. [DOI] [PubMed] [Google Scholar]
  22. Romero-Herrera A. E., Lehmann H., Joysey K. A., Friday A. E. Molecular evolution of myoglobin and the fossil record: a phylogenetic synthesis. Nature. 1973 Dec 14;246(5433):389–395. doi: 10.1038/246389a0. [DOI] [PubMed] [Google Scholar]
  23. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sawada I., Beal M. P., Shen C. K., Chapman B., Wilson A. C., Schmid C. Intergenic DNA sequences flanking the pseudo alpha globin genes of human and chimpanzee. Nucleic Acids Res. 1983 Nov 25;11(22):8087–8101. doi: 10.1093/nar/11.22.8087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schmid C. W., Jelinek W. R. The Alu family of dispersed repetitive sequences. Science. 1982 Jun 4;216(4550):1065–1070. doi: 10.1126/science.6281889. [DOI] [PubMed] [Google Scholar]
  26. Whitelaw E., Proudfoot N. J. Transcriptional activity of the human pseudogene psi alpha globin compared with alpha globin, its functional gene counterpart. Nucleic Acids Res. 1983 Nov 25;11(22):7717–7733. doi: 10.1093/nar/11.22.7717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wilbur W. J., Lipman D. J. Rapid similarity searches of nucleic acid and protein data banks. Proc Natl Acad Sci U S A. 1983 Feb;80(3):726–730. doi: 10.1073/pnas.80.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zweig S. E. Analysis of large nucleic acid dot matrices on small computers. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):767–776. doi: 10.1093/nar/12.1part2.767. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES