Summary
A 6.0-kb DNA fragment from Gorilla gorilla including the 5′ part of the β-globin gene and about 4.5 kb of its upstream flanking region was cloned and sequenced. The sequence was compared to the human, chimpanzee, and macaque δ-β intergenic region. This analysis reveals four tandemly repeated sequences (RS), at the same location in the four species, showing a variable number of repeats generating both intraspecific (polymorphism) and interspecific variability. These tandem arrays delimit five regions of unique sequence called IG for intergenic. The divergence for these IG sequences is 1.85 ± 0.22% between human and gorilla, which is not significantly different from the value estimated in the same region between chimpanzee and human (1.62 ± 0.21%). The CpG and TpA dinucleotides are avoided. CpGs evolve faster than other sequence sites but do not confuse phylogenetic inferences by producing parallel mutations in different lineages. About 75% of CpG doublets have become TpG or CpA since the common ancestor, in agreement with the methylation/deamination pattern. Comparison of this intergenic region gives information on branching order within Hominoidea. Parsimony and distance-based methods when applied to the δ-β intergenic region provide evidence (although not statistically significant) that human and chimpanzee are more closely related to each other than to gorilla. CpG sites are indeed rich in information by carrying substitutions along the short internal branch. Combining these results with those on the ψη—δ intergenic region, shows in a statistically significant way that chimpanzee is the closest relative of human.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Berg PE, Williams DM, Qian RL, Cohen RB, Cao SK, Mittelman M, Schechter AN (1989) A common protein binds to two silencers 5′ to the human β globin gene. Nucleic Acids Res 17:8833–8852
Biggin MD, Gibson TJ, Hong GF (1983) Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci USA 80:3963–3965
Bird AP (1980) DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res 8:1499–1504
Bird AP, Taggart MH, Nicholls RD, Higgs DR (1987) Nonmethylated CpG rich islands at the human α-globin locus: implications for evolution of a α-globin pseudogene. EMBO J 6:999–1004
Boudraa M, Perrin P (1987) CpG and TpA frequencies in the plant system. Nucleic Acids Res 15:5729–5737
Brewer AC, Enver T, Greaves DR, Allan J, Patient RK (1988) 5′ structural motifs and Xenopus β-globin gene activation. J Mol Biol 199:575–585
Broderick TP, Schaff DA, Bertino AM, Dush MK, Tischfield JA, Stambrook PJ (1987) Comparative anatomy of the human APRT gene and enzyme: nucleotide sequence divergence and conservation of a nonrandom CpG dinucleotide arrangement. Proc Natl Acad Sci USA 84:3349–3353
Brown WM, Prager EM, Wang A, Wilson AC (1982) Mitochondrial DNA sequences of primates: tempo and mode of evolution. J Mol Evol 18:225–239
Caccone A, Powell JR (1989) DNA divergence among hominoids. Evolution 43:925–942
Chebloune Y, Pagnier J, Trabuchet G, Faure C, Verdier G, Labie D, Nigon V (1988) Structural analysis of the 5'-flanking region of the β-globin gene in African sickle cell anemia patients: further evidence for three origins of the sickle cell mutation in Africa. Proc Natl Acad Sci USA 85:4431–4435
Collins FS, Weissman SM (1984) The molecular genetics of human hemoglobin. Prog Nucleic Acids Res Mol Biol 31: 315–462
Cooper DN, Gerber-Huber S (1985) DNA methylation of CpG suppression. Cell Diff 17:199–205
Cooper DN, Gerber-Huber S, Nardelli D, Schubiger JL, Wahli W (1987) The distribution of the dinucleotide CpG and cytosine methylation in the vitellogenin gene family. J Mol Evol 25:107–115
Coulondre C, Miller JH, Farabaugh PJ, Gilbert W (1978) Molecular basis of base substitution hotspots in Escherichia coli. Nature 274:775–780
Doerfler W (1983) DNA methylation and gene activity. Annu Rev Biochem 52:93–124
Economou EP, Bergen AW, Warren AC, Antonarakis SE (1990) The polydeoxyadenylate tract of Alu repetitive element is polymorphic in the human genome. Proc Natl Acad Sci USA 87:2951–2954
Ellis N, Yen P, Neiswanger K, Shapiro LJ, Goodfellow PN (1990) Evolution of the pseudoautosomal boundary in Old World monkeys and great apes. Cell 63:977–986
Felsenstein J (1988a) Phylogenies from molecular sequences: inference and reliability. Annu Rev Genet 22:521–565
Felsenstein J (1988b) PHYLIP version 3–3 manual. University of Washington, Seattle
Fitch WM (1971) Toward defining the course of evolution: minimum change for a specific tree topology. Syst Zool 20: 406–416
Fitch WM, Mainone C, Slightom JL, Goodman M (1988) The spider monkey ψη-globin gene and surrounding sequences: recent or ancient insertions of LINE'S and SINEs? Genomics 3:237–255
Gautier C, Gouy M, Louail S (1985) Non-parametric statistics for nucleic acid sequence study. Biochimie 67:449–453
Gonzalez IL, Sylvester JE, Smith TF, Stambolian D, Schmickel RD (1990) Ribosomal RNA gene sequences and hominoid phylogeny. Mol Biol Evol 7:203–219
Goodman M, Koop BF, Czelusniak J, Fitch DHA, Tagle DA, Slightom JL (1989) Molecular phylogeny of the family of apes and humans. Genome 31:316–335
Goodman M, Tagle DA, Fitch DHA, Bailey W, Czelusniak J, Koop BF, Benson P, Slightom JL (1990) Primate evolution at the DNA level and a classification of hominoids. J Mol Evol 30:260–266
Gouy M, Milleret F, Mugnier C, Jacobzone M, Gautier C (1984) ACNUC: a nucleic acid sequence data base and analysis system. Nucleic Acids Res 12:121–127
Gouy M, Gautier C, Milleret F (1985) System analysis and nucleic acid sequence banks. Biochimie 67:433–436
Grantham R, Greenland T, Louail S, Mouchiroud D, Prato JL, Gouy M, Gautier C (1985) Molecular evolution of viruses as seen by nucleic acid sequence study. Bull Inst Pasteur 83: 95–148
Grantham R, Perrin P, Mouchiroud D (1986) Patterns in codon usage of different kinds of species. Oxford Surv Evol Biol 3: 48–81
Green PM, Montandon AJ, Bentley DR, Ljung R, Nilsson IM, Giannelli F (1990) The incidence and distribution of CpG-TpG transitions in the coagulation factor IX gene. A fresh look at CpG mutation hotspots. Nucleic Acids Res 18:3227–3231
Hasegawa M, Kishino H, Hayasaka K, Horai S (1990) Mitochondrial DNA evolution in primates: transition rate has been extremely low in the lemur. J Mol Evol 31:113–121
Hasson JF, Mougneau E, Cuzin F, Yaniv M (1984) Simian virus 40 illegitimate recombination occurs near short direct repeats. J Mol Biol 177:53–69
Hayasaka K, Gojobori T, Horai S (1988) Molecular phylogeny and evolution of primate mitochondria DNA. Mol Biol Evol 5:626–644
Holmquist R, Miyamoto MM, Goodman M (1988a) Higherprimate phylogeny-why can't we decide? Mol Biol Evol 5: 201–216
Holmquist R, Miyamoto MM, Goodman M (1988b) Analysis of higher-primate phylogeny from transversion differences in nuclear and mitochondrial DNA by Lake's methods of evolutionary parsimony and operator metrics. Mol Biol Evol 5: 217–236
Jukes TH (1987) Transitions, transversions and the molecular evolutionary clock. J. Mol Evol 26:87–98
Kimura M (1981) Estimation of evolutionary distance between homologous nucleotide sequences. Proc Natl Acad Sci USA 78:454–458
Kolata G (1985) Fitting methylation into development. Science 228:1183–1184
Kolsto AB, Kollias G, Giguere V, Isobe KI, Prydz H, Grosveld F (1986) The maintenance of methylation-free islands in transgenic mice. Nucleic Acids Res 14:9667–9678
Koop BF, Tagle DA, Goodman M, Slightom JL (1989) A molecular view of primate phylogeny and important systematic and evolutionary questions. Mol Biol Evol 6:580–612
Li WH, Wolfe KH, Sourdis J, Sharp PM (1987) Reconstruction of phylogenetic trees and estimation of divergence times under unconstant rates of evolution. Cold Spring Harbor Symp Quant Biol LII:847–856
Li WH (1989) A statistical test of phylogenies estimated from sequence data. Mol Biol Evol 6:424–435
Lindahl T (1981) DNA methylation and control of gene expression. Nature 290:363–364
Maeda N, Bliska JB, Smithies O (1983) Recombination and balanced chromosome polymorphism suggested by DNA sequences 5′ to the human β-globin gene. Proc Natl. Acad Sci USA 80:5012–5016
Maeda N, Wu CI, Bliska J, Reneke J (1988) Molecular evolution of intergenic DNA in higher primates: pattern of DNA changes, molecular clock, and evolution of repetitive sequences. Mol Biol Evol 5:1–20
Margot JB, Demers JW, Hardison RC (1989) Complete nucleotide sequence of the rabbit β-like globin gene cluster. Analysis of intergenic sequences and comparison with the human β-like globin gene cluster. J Mol Biol 205:15–110
McKeon C, Ohkubo H, Pastan I, de Crombrugghe B (1982) Unusual methylation pattern of the α2(I) collagen gene. Cell 29:203–210
Messing J, Vieira J(1982) A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene 19:269–276
Misfield R, Krystal M, Arnheim N (1981) A member of a new repeated segment sequence family which is conserved throughout eucaryotic evolution is found between the human delta and beta-globin genes. Nucleic Acids Res 9:5931–5947
Miyamoto MM, Slightom JL, Goodman M (1987) Phylogenetic relations of humans and African apes from DNA sequences in the ψη-globin region. Science 238:369–373
Nei M (1987) Parsimony methods. In: Molecular evolutionary genetics. Columbia University Press, New York, p 313–320
Perrin P, Bernardi G (1987) Directional fixation of mutations in vertebrate evolution. J Mol Evol 26:301–310
Perutz MF (1990) Frequency of abnormal human hemoglobins caused by C → T transitions in CpG dinucleotides. J Mol Biol 213:203–206
Poncz M, Schwartz E, Ballantine M, Surrey S (1983) Nucleotide sequence analysis of the delta-beta globin gene region in humans. J Biol Chem 258:11599–11609
Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425
Sanger F, Coulson AR, Barrell BG, Smith AJH, Roe BA (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467
Savatier P, Trabuchet G, Faure C, Chebloune Y, Gouy M, Verdier G, Nigon VM (1985) Evolution of the primate betaglobin gene region: high rate of variation in CpG dinucleotides and in short repeated sequences between man and chimpanzee. J Mol Biol 182:21–29
Savatier P, Trabuchet G, Chebloune Y, Faure C, Verdier G, Nigon V (1987a) Nucleotide sequence of the delta-beta globin intergenic segment in the macaque: structure and evolutionary rates in higher primates. J Mol Evol 24:297–308
Savatier P, Trabuchet G, Chebloune Y, Faure C, Verdier G, Nigon VM (1987b) Nucleotide sequence of the beta-globin genes in gorilla and macaque: the origin of nucleotide polymorphisms in man. J Mol Evol 24:309–318
Semenza GL, Malladi P, Surrey S, Delgrosso K, Poncz M, Schwartz E (1984) Detection of a novel DNA polymorphism in the β globin gene cluster. J Biol Chem 259:6045–6048
Shehee WR, Loeb DD, Adey NB, Burton FH, Casavant NC, Cole P, Davies CJ, McGraw RA, Schichman SA, Severynse DM, Voliva CF, Weyter FW, Wisely GB, Edgell MH, Hutchinson CA III (1989) Nucleotide sequence of the BALB/c mouse β-globin complex. J Mol Biol 205:41–62
Sibley CG, Ahlquist JE (1984) The phylogeny of the hominoid primates, as indicated by DNA-DNA hybridization. J Mol Evol 20:2–15
Sibley CG, Ahlquist JE (1987) DNA hybridization evidence of hominoid phylogeny: results from an expanded data set. J Mol Evol 26:99–121
Sibley CG, Comstock JA, Ahlquist JE (1990) DNA hybridization evidence of hominoid phylogeny: a reanalysis of the data. J Mol Evol 30:202–236
Smith TF, Waterman MS (1981) Comparison of biosequences. Adv Appl Math 2:482–489
Smith TF, Ralph WW, Goodman, M, Czelusniak J (1985) Codon usage in the vertebrate hemoglobins and its implications. Mol Biol Evol 2:390–398
Spritz RA (1981) Duplication/deletion polymorphism 5′ to the human β-globin gene. Nucleic Acids Res 9:5037–5047
Tabor S, Richardson C (1987) DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci USA 84:4767–4771
Tautz D (1989) Hypervariability of simple sequences as a general source for polymorphic DNA markers. Nucleic Acids Res 17:6463–6471
Tazi J, Bird A (1990) Alternative chromatin structure at CpG islands. Cell 60:909–920
Trabuchet G, Chebloune Y, Savatier P, Lachuer J, Faure C, Verdier G, Nigon VM (1987) Recent insertion of an Alu sequence in the beta-globin cluster of the gorilla. J Mol Evol 25:288–291
Trabuchet G, Elion J, Baudot G, Pagnier J, Bouhass R, Nigon VM, Labie D, Krishnamoorthy R (1991) On the origin and spread of beta-globin gene mutations in India, Africa and Mediterranea: analysis of the 5'-flanking and intragenic sequences of beta S and beta C genes. Hum Biol 63:241–252
Tykocinski ML, Max EE (1984) CG dinucleotide clusters in MHC genes and in 5′ demethylated genes. Nucleic Acids Res 12:4385–4396
Ueda S, Matsuda F, Honjo T (1988) Multiple recombinational events in primate immunoglobulin-epsilon and alpha genes suggest closer relationship of humans to chimpanzees than to gorillas. J Mol Evol 27:77–83
Ueda S, Watanabe Y, Saitou N, Omoto K, Hayashida H, Miyata T, Hisajima H, Honjo T (1989) Nucleotide sequences of immunoglobulin-epsilon pseudogenes in man and apes and their phylogenetic relationships. J Mol Biol 205:85–90
Williams SA, Goodman G (1989) A statistical test that supports a human/chimpanzee clade based on noncoding DNA sequence data. Mol Biol Evol 6:325–330
Wolf SF, Migeon BR (1985) Clusters of CpG dinucleotides implicated by nuclease hypersensitivity as control for housekeeping genes. Nature 314:467–469
Youssoufian H, Kazazian HH Jr, Phillips DG, Aronis S, Tsiftis G, Brown VA, Antonarakis SE (1986) Recurrent mutations in haemophilia A give evidence for CpG mutation hotspots. Nature 324:380–382
Author information
Authors and Affiliations
Additional information
Offprint requests to: P. Perrin-Pecontal
Rights and permissions
About this article
Cite this article
Perrin-Pecontal, P., Gouy, M., Nigon, VM. et al. Evolution of the primate β-Globin gene region: Nucleotide sequence of the δ-β-globin Intergenic region of gorilla and phylogenetic relationships between African Apes and Man. J Mol Evol 34, 17–30 (1992). https://doi.org/10.1007/BF00163849
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00163849