Abstract
In sheep as in man and most other mammals, there are two α-globin genes (Iα and IIα), which are expressed at different levels, the upstream gene being the most efficient. In α-globin gene triplication and quadruplication, this trend is confirmed, i.e., the α-chain output of the downstream genes progressively decreases. In this study, we have determined the complete sequence of the cDNAs and of both the introns in a triple-α haplotype in which each gene could be recognized for the presence of distinct alleles. The sequence analysis reveals that the bodies of the three α-globin genes are essentially identical (99.9% homology) and moreover indicates that the down-regulation of additional α-globin genes in sheep is not the effect of sequence variation from the Cap to the Poly(A) addition sites. This striking similarity among α-genes is higher than that seen in other mammals and is probably sustained by particularly efficient mechanisms of gene conversion and cross-over fixation.
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Flint J, Hill AVS, Dowden DK, Oppenheimer SJ, Sill PR, Serjeantson SW, Bana-Koiri J, Bhatia K, Alpers MJ, Boyce AJ, Wetherall DJ, Clegg JB (1986) High frequencies of a thalassemia are the result of natural selection by malaria. Nature 321:744–750
Frohman MA (1990) RACE: rapid amplification of cDNA ends. In: Innis MA, Gelfand DH, Sninsky JJ, White JJ (eds) PCR Protocols. pp 28–38
Hardison R, Cheng JF, Demers GW, Margot JB (1987) Rabbit α like and β like globin gene clusters: comparisons among mammalian globin gene clusters. In: Developmental control of globin gene expression. Alan R Liss, New York, pp 91–105
Higgs DR, Wood WG, Jarman AP, Sharpe J, Lida J, Pretorius IM, Ayyud H (1990). A major positive regulatory region located far upstream of the human α-globin gene locus. Genes Dev 4:1588–1601
Huisman THJ, Dozy AM, Wilson JB, Efremov GD, Vaskov B (1968) Sheep hemoglobin D, an α-chain variant with one apparent amino acid substitution (α15Gly-Asp). Biochim Biophys Acta 160:467–469
Kadesh T, Berg P (1986) Effect of the position of the simian virus 40 enhancer on expression of multiple transcription units in a single plasmid. Mol Cell Biol 6:2593–2601
Liebhaber SA, Gossens MJ, Kan YW (1981) Homology and concerted evolution of the α1 and α2 loci of the human α-globin. Nature 290:26–29
Liebhaber SA, Kan YW (1981) Differentiation of mRNA transcripts originating from the α1 and α2-genes in normals and α-thalassemics. J Clin Invest 68:439–448
Liebhaber SA, Cash FE, Ballas SK (1986) Human alfa globin gene expression. J Biol Chem 261:15327–15333
Michelson AM, Orkin SH (1983) Boundaries of gene conversion within the duplicated human α-globin genes. J Biol Chem 258: 15245–15253
Modiano G, Morpurgo G, Terrenato L, Novelletto A, Di Rienzo A, Colombo B, Purpura M, Mariani M, Santachiara-Benerecetti S, Brega A, Dixit KA, Shrestha SL, Lania A, Wanachiwanawin W, Luzzato L (1991) Protection against malaria morbidity: nearfixation of the α thalassemia gene in a Nepalese population. Am J Hum Genet 48:390–397
Pondel MD, George M, Proudfoot NJ (1992) The LCR-like α-globin positive regulatory element functions as an enhancer in transiently transfected cells during erythroid differentiation. Nucleic Acid Res 20:237–243
Proudfoot NJ (1986) Transcriptional interference and termination between duplicated α-globin gene constructs suggests a novel mechanism of gene regulation. Nature 322:562–565
Rando A, Ramunno L, Masina P (1986) Variation of the number of α globin loci in sheep. Mol Biol Evol 3:168–176
Sambrook J, Fritsh EF, Maniatis T (1989) Molecular cloning-⊕ laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
Schon EA, Wernke SM, Lingrel JB (1982) Gene conversion of two functional goat α-globin genes preserves only minimal flanking sequences. J Biol Chem 257:6825–6835
Vestri R, Giordano PC, Bernini LF (1983) Different quantitative Expression of the hemoglobin α-chain genes in sheep. Biochem Genet 21:1089–1099
Vestri R, Pieragostini E, Yang F, Di Gregorio P, Rando A, Masina P (1991) Expression of triplicated and quadruplicated α globin genes in sheep. Br J Haematol 77:110–116
Vestri R, Pieragostini E, Ristaldi MS (1994) Expression popgradient in sheep αα and ααα globin gene haplotypes: mRNA levels. Blood 83:2317–2322
Wilson JB, Brandt G, Hisman THJ (1968) The structure of sheep hemoglobins. III. Structural studies of the a chain of hemoglobin A. J Biol Chem 243:3687–3692
Wood WI, Gitschier J, Lasky LA, Lawn RM (1985) Base composition independent hybridization in tetramethylammonium chloride: a method for oligonucleotide screening of high complex gene libraries. Proc Natl Acad Sci USA 82:1585–1588
Zimmer EA, Martin SL, Beverly SM, Kan YW, Wilson AC (1980) Rapid duplication and loss of genes coding for the α chains of the hemoglobin. Proc Natl Acad Sci USA 77:2158–2162
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Correspondence to: Dr. M.S. Ristaldi
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Ristaldi, M.S., Casula, S., Rando, A. et al. Sheep α-globin gene sequences: Implications for their concerted evolution and for the down-regulation of the 3′ genes. J Mol Evol 40, 349–353 (1995). https://doi.org/10.1007/BF00164020
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DOI: https://doi.org/10.1007/BF00164020