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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Jan;79(2):550–554. doi: 10.1073/pnas.79.2.550

Genetic variation in natural populations: problem of electrophoretically cryptic alleles.

F J Ayala
PMCID: PMC345782  PMID: 6804943

Abstract

Electrophoretic studies have shown that the average frequency of heterozygous loci per individual is about 12% in Drosophila and other invertebrates and about 6% in vertebrates. It is estimated that only about two-thirds of all amino acid substitutions change net electric charge; hence, a large fraction of all genetic variation may be undetected by electrophoresis. Peptide mapping of 11 independent alleles coding for alcohol dehydrogenase in Drosophila melanogaster has uncovered one cryptic variant; thus, the frequency of electrophoretically cryptic variation is apparently low, about 9% in this sample. Nevertheless, with a simple model it is shown that this degree of cryptic variation, if it is typical of other loci, would substantially change our current estimates of genetic variation: the average heterozygosity would increase from about 12% to about 25% for invertebrates and from about 6% to 21% for vertebrates. A variety of techniques--including sequential electrophoresis and heat or urea denaturation--have been used by various investigators to detect electrophoretically cryptic variation. These techniques appear to be less effective than peptide mapping for detecting cryptic variation, but, like peptide mapping, they suggest that standard electrophoresis may detect most of the protein variation present in natural populations. The charge-state model of protein variation proposes that the "alleles" detected by electrophoresis are extremely diverse classes consisting of many electrophoretically cryptic alleles. The alcohol dehydrogenase peptide-mapping results are inconsistent with the charge-state model.

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Selected References

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

  1. Beckenbach A. T., Prakash S. Examination of Allelic Variation at the Hexokinase Loci of DROSOPHILA PSEUDOOBSCURA and D. PERSIMILIS by Different Methods. Genetics. 1977 Dec;87(4):743–761. doi: 10.1093/genetics/87.4.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Britten R. J., Cetta A., Davidson E. H. The single-copy DNA sequence polymorphism of the sea urchin Strongylocentrotus purpuratus. Cell. 1978 Dec;15(4):1175–1186. doi: 10.1016/0092-8674(78)90044-2. [DOI] [PubMed] [Google Scholar]
  3. Cochrane B. J., Richmond R. C. Studies of esterase-6 in Drosophila melanogaster. II. The genetics and frequency distributions of naturally occurring variants studied by electrophoretic and heat stability criteria. Genetics. 1979 Oct;93(2):461–478. doi: 10.1093/genetics/93.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coyne J. A., Felton A. A. Genic Heterogeneity at Two Alcohol Dehydrogenase Loci in DROSOPHILA PSEUDOOBSCURA and DROSOPHILA PERSIMILIS. Genetics. 1977 Oct;87(2):285–304. doi: 10.1093/genetics/87.2.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coyne J. A., Felton A. A., Lewontin R. C. Extent of genetic variation at a highly polymorphic esterase locus in Drosophila pseudoobscura. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5090–5093. doi: 10.1073/pnas.75.10.5090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fletcher T. S., Ayala F. J., Thatcher D. R., Chambers G. K. Structural analysis of the ADHS electromorph of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5609–5612. doi: 10.1073/pnas.75.11.5609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kimura M., Ohta T. Protein polymorphism as a phase of molecular evolution. Nature. 1971 Feb 12;229(5285):467–469. doi: 10.1038/229467a0. [DOI] [PubMed] [Google Scholar]
  8. King J. L. Isoallele frequencies in very large populations. Genetics. 1974 Mar;76(3):607–613. doi: 10.1093/genetics/76.3.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. King J. L. The probability of electrophoretic idendity of proteins as a function of amino acid divergence. J Mol Evol. 1973 Nov 27;2(4):317–322. doi: 10.1007/BF01654099. [DOI] [PubMed] [Google Scholar]
  10. Kreitman M. Assessment of variability within electromorphs of alcohol dehydrogenase in Drosophila melanogaster. Genetics. 1980 Jun;95(2):467–475. doi: 10.1093/genetics/95.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Loukas M., Vergini Y., Krimbas C. B. The genetics of Drosophila subobscura populations. XVII. Further genic heterogeneity within electromorphs by urea denaturation and the effect of the increased genic variability on linkage disequilibrium studies. Genetics. 1981 Feb;97(2):429–441. doi: 10.1093/genetics/97.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Marshall D. R., Brown A. H. The charge-state model of protein polymorphism in natural populations. J Mol Evol. 1975 Nov 4;6(3):149–163. doi: 10.1007/BF01732353. [DOI] [PubMed] [Google Scholar]
  13. Ohta T., Kimura M. A model of mutation appropriate to estimate the number of electrophoretically detectable alleles in a finite population. Genet Res. 1973 Oct;22(2):201–204. doi: 10.1017/s0016672300012994. [DOI] [PubMed] [Google Scholar]
  14. Ramshaw J. A., Coyne J. A., Lewontin R. C. The sensitivity of gel electrophoresis as a detector of genetic variation. Genetics. 1979 Dec;93(4):1019–1037. doi: 10.1093/genetics/93.4.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sampsell B. Isolation and genetic characterization of alcohol dehydrogenase thermostability variants occurring in natural populations of Drosophila melanogaster. Biochem Genet. 1977 Oct;15(9-10):971–988. doi: 10.1007/BF00483992. [DOI] [PubMed] [Google Scholar]
  16. Satoh C., Mohrenweiser H. W. Genetic heterogeneity within an electrophoretic phenotype of phosphoglucose isomerase in a Japanese population. Ann Hum Genet. 1979 Jan;42(3):283–292. doi: 10.1111/j.1469-1809.1979.tb00662.x. [DOI] [PubMed] [Google Scholar]
  17. Schwartz M. F., Jörnvall H. Structural analyses of mutant and wild-type alcohol dehydrogenases from drosophila melanogaster. Eur J Biochem. 1976 Sep;68(1):159–168. doi: 10.1111/j.1432-1033.1976.tb10774.x. [DOI] [PubMed] [Google Scholar]
  18. Singh R. S. Genic heterogeneity within electrophoretic "alleles" and the pattern of variation among loci in Drosophila pseudoobscura. Genetics. 1979 Dec;93(4):997–1018. doi: 10.1093/genetics/93.4.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Slightom J. L., Blechl A. E., Smithies O. Human fetal G gamma- and A gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell. 1980 Oct;21(3):627–638. doi: 10.1016/0092-8674(80)90426-2. [DOI] [PubMed] [Google Scholar]
  20. Thatcher D. R. The complete amino acid sequence of three alcohol dehydrogenase alleloenzymes (AdhN-11, AdhS and AdhUF) from the fruitfly Drosophila melanogaster. Biochem J. 1980 Jun 1;187(3):875–883. doi: 10.1042/bj1870875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Trippa G., Loverre A., Catamo A. Thermostability studies for investigating non-electrophoretic polymorphic alleles in Drosophila melanogaster. Nature. 1976 Mar 4;260(5546):42–44. doi: 10.1038/260042a0. [DOI] [PubMed] [Google Scholar]
  22. Wehrhahn C. F. The evolution of selectively similar electrophoretically detectable alleles in finite natural populations. Genetics. 1975 Jun;80(2):375–394. doi: 10.1093/genetics/80.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]

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