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Point mutations and human hemoglobin variants

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Summary

More than one hundred hemoglobin variants with single amino acid substitutions give information about point mutations in the DNA structure of the hemoglobin cistrons.

Using the available data on the genetic code we concluded:

  1. 1.

    All single amino acid substitutions in human hemoglobin variants are compatible with the hypothesis that only one base is replaced in the DNA codon.

  2. 2.

    On the basis of this hypothesis, a number of possible condons in the \ga-, \gb-, \gg-, and \gd-chains can be excluded. This might be regarded as a first step towards a genetic sequence analysis of the hemoglobin cistrons.

  3. 3.

    Transitions as well as transversions are observed. However, the number of transitions is significantly higher than expected, if base replacement would be random. This result is not caused by the well known bias in ascertainment of human hemoglobins due to the fact that most variants are detected by a deviation in electrophoretic mobility.

    It is mainly, if not exclusively due to the cytosine—thymine transition in the DNA code. A prevalence of the same transition is also observed when amino acid differences between myoglobin and human α-, γ-, and β-chains are compared. Surprisingly, a corresponding increase in the frequency of the guanine—adenine transition was not observed. This seems to point to a relationship between mutating and coding strand within the DNA double helix.

  4. 4.

    As a side result of the comparisons between myoglobin, \ga-, \gg-, and \gb-chains, it turned out, that among the amino acid substitutions between myoglobin and the \ga-chain, those which are compatible and incompatible with a single base replacement within the DNA code are not distributed at random. There are too few (and too long) runs of incompatible substitutions. This could be due to partially incorrect amino acid pairing in the scheme proposed by Braunitzer.

  5. 5.

    Positions in \ga- and \gb-chains for which two, three, or more amino acid replacements were observed are not more frequent than expected, if distributions of replacement would be random.

  6. 6.

    There is no clustering of detected mutations in adjacent codons.

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References

  • Beale, D., and H. Lehmann: Abnormal haemoglobin and the genetic code. Nature (Lond.) 207, 259–261 (1965).

    Google Scholar 

  • Braunitzer, G.: Die Primärstruktur der Eiweißstoffe. Naturwissenschaften 15/16, 407–417 (1967).

    Google Scholar 

  • Cold Spring Harbor Symposia XXXI. Cold Spring Harbor, New York 1966.

  • Dayhoff, M. O., and R. V. Eck: Atlas of protein sequence and structure, 1967–1968. National Biochemical Research Foundation. Silver Spring 1968.

    Google Scholar 

  • Dellweg, B.: Molekularbiologische Betrachtungen zur Hämoglobinsynthese. Dtsch. med. Wschr. 92, 1826–1831 (1967).

    Google Scholar 

  • Fitch, W. M.: Evidence suggesting a non-random character to nukleotide replacements in naturally occurring mutations. J. molec. Biol. 26, 499–507 (1967).

    Google Scholar 

  • Giblett, E.: Genetic markers in human blood. Oxford: Blackwell 1968.

    Google Scholar 

  • Huehns, E. R., and E. M. Shooter: Human haemoglobins. J. med. Genet. 2, 48–90 (1965).

    Google Scholar 

  • Kimura, M.: Evolutionary rate at the molecular level. Nature (Lond.) 217, 624–626 (1968).

    Google Scholar 

  • Lehmann, H., and R. W. Carrell: Variations in the structure of human haemoglobin. Brit. med. Bull. 25, 14–23 (1969).

    Google Scholar 

  • Motulsky, A. G.: Personal communication 1968.

  • Perutz, M. F., and H. Lehmann: Molecular pathology of human haemoglobin. Nature (Lond.) 219, 902 (1968).

    Google Scholar 

  • —, H. Muirhead, J. M. Cox, and L. C. G. Goaman: Threedimensional fourier synthesis of horse oxyhaemoglobin at 2.8A resolution. The atomic model. Nature (Lond.) 219, 131 (1968).

    Google Scholar 

  • Rahmel, U.: Mathematische Analyse eines Code-Problems aus der Molekularbiologie. Göttingen: Unpubl. Saatsexamensarbeit 1968.

    Google Scholar 

  • Siegel, S.: Nonparametric statistics for the behavioural science. New York-Toronto-London: McGraw-Hill Book Company 1956.

    Google Scholar 

  • Vogel, F., and G. Röhrborn: Mutationsvorgänge bei der Entstehung von Hämoglobinvarianten. Humangenetik 1, 635–650 (1965).

    Google Scholar 

  • —: Amino acid substitutions in haemoglobins and the mutation process. Nature (Lond.) 210, 116–117 (1966).

    Google Scholar 

  • Wintrobe, M. M.: Clinical Hematology. Philadelphia: Lea and Febiger 1967.

    Google Scholar 

  • Yanofsky, C., J. Ito, and V. Horn: Amino acid replacements and the genetic code. Cold Spr. Harb. Symp. quant. Biol. 31, 151–162 (1966).

    Google Scholar 

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Authors and Affiliations

  1. Institute of Anthropology and Human Genetics, University of Heidelberg, Germany

    F. Vogel

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  1. F. Vogel
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Vogel, F. Point mutations and human hemoglobin variants. Hum Genet 8, 1–26 (1969). https://doi.org/10.1007/BF00286751

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  • DOI: https://doi.org/10.1007/BF00286751

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