Can the product of the theta gene be a real globin?
Abstract: A new member (theta 1, or psi alpha) of the alpha-globin gene family has recently been identified in a number of species. In higher primates the theta 1 gene has all the structural features apparently necessary for expression, and it appears to have long been under strong selective constraints which suggests that it could still be, or recently have been, a functional gene. No corresponding 'globin' has yet been identified, however. In some other species, galago and rabbit for example, the theta 1 and psi alpha genes have accumulated enough inactivating mutations for them to be considered genuine pseudogenes. Horses also have an alpha-like gene (psi alpha), in a 3' position identical to the other species in relation to the functional alpha genes, and this also appears to have the elements required for a functional gene. The predicted amino-acid sequence, however, suggests that any 'globin' product is likely to be non-viable because it has a number of seriously deleterious amino-acid replacements. Some of these amino-acid changes are shared with the rabbit and primate sequences, indicating that they predate the mammalian radiation, and that if indeed any of these genes are still functional, they are unlikely to be making haemoglobin.
Publication Date: 1987-10-01 PubMed ID: 3657962DOI: 10.1038/329465a0Google Scholar: Lookup
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- Comparative Study
- Journal Article
Summary
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The article explores the potential for the product of the theta gene to be a real globin. It indicates that while some species show signs of the possibility, the predicted amino acid sequence suggests a non-viable ‘globin’ product.
Research Context
- The study delves into a newly discovered member of the alpha-globin gene family identified in several species, known as the theta 1 or psi alpha gene.
- In higher primates, this gene appears to possess all necessary structural features for expression and has seemingly been under significant selective constraints, suggesting that the gene might be functional or could recently have been functional. However, no corresponding ‘globin’ has yet been recognized.
Study Findings on Different Species
- In galagos and rabbits, the theta 1 and psi alpha genes have accumulated enough inactivating mutations to classify them as pseudogenes, which means they’re genomic DNA sequences similar to normal genes but are non-functional.
- Horses also possess an alpha-like gene (psi alpha) positioned similarly to other species in relation to functional alpha genes, indicating possible functionality. However, the predicted amino-acid sequences hint at a non-viable ‘globin’ product due to severe deleterious amino-acid replacements.
Evolutionary Insights
- Some of these amino-acid changes are seen across rabbit and primate sequences, signifying they predate the mammalian radiation – the rapid diversification of mammals that occurred around 66 million years ago in the Cenozoic Era.
- This widespread presence suggests that if any of these genes are still functional, they likely do not produce haemoglobin – a protein in red blood cells that carries oxygen.
Conclusion
- The research raises doubts about the functionality of the theta gene in producing viable globin, suggesting further investigation and comparative analysis across different species is needed to fully understand the patterns of these genetic sequences.
Cite This Article
APA
Clegg JB.
(1987).
Can the product of the theta gene be a real globin?
Nature, 329(6138), 465-466.
https://doi.org/10.1038/329465a0 Publication
Researcher Affiliations
- MRC Molecular Haematology Unit, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, UK.
MeSH Terms
- Amino Acid Sequence
- Animals
- Base Sequence
- Codon
- Genes
- Globins / genetics
- Horses
- Humans
- Molecular Sequence Data
- Pongo pygmaeus
- Rabbits
Citations
This article has been cited 8 times.- Zittersteijn HA, Harteveld CL, Klaver-Flores S, Lankester AC, Hoeben RC, Staal FJT, Gonçalves MAFV. A Small Key for a Heavy Door: Genetic Therapies for the Treatment of Hemoglobinopathies.. Front Genome Ed 2020;2:617780.
- Hardison RC. Evolution of hemoglobin and its genes.. Cold Spring Harb Perspect Med 2012 Dec 1;2(12):a011627.
- Cooper SJ, Wheeler D, Hope RM, Dolman G, Saint KM, Gooley AA, Holland RA. The alpha-globin gene family of an Australian marsupial, Macropus eugenii: the long evolutionary history of the theta-globin gene and its functional status in mammals.. J Mol Evol 2005 May;60(5):653-64.
- Goh SH, Lee YT, Bhanu NV, Cam MC, Desper R, Martin BM, Moharram R, Gherman RB, Miller JL. A newly discovered human alpha-globin gene.. Blood 2005 Aug 15;106(4):1466-72.
- Gonzalez-Redondo JM, Han IS, Gu YC, Huisman TH. Nucleotide sequence of the human theta 1-globin gene.. Biochem Genet 1988 Apr;26(3-4):207-11.
- Ley TJ, Maloney KA, Gordon JI, Schwartz AL. Globin gene expression in erythroid human fetal liver cells.. J Clin Invest 1989 Mar;83(3):1032-8.
- Leung SO, Whitelaw E, Proudfoot NJ. Transcriptional and translational analysis of the human theta globin gene.. Nucleic Acids Res 1989 Oct 25;17(20):8283-300.
- Kim JH, Yu CY, Bailey A, Hardison R, Shen CK. Unique sequence organization and erythroid cell-specific nuclear factor-binding of mammalian theta 1 globin promoters.. Nucleic Acids Res 1989 Jul 25;17(14):5687-700.
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