Skip to main content
Genetics logoLink to Genetics
. 1997 Apr;145(4):1003–1013. doi: 10.1093/genetics/145.4.1003

Genomic Organization and Evolution of Alternative Exons in a Drosophila Calcium Channel Gene

A A Peixoto 1, L A Smith 1, J C Hall 1
PMCID: PMC1207871  PMID: 9093853

Abstract

The genomic organization of a gene coding for an α1 subunit of a voltage-gated calcium channel of Drosophila melanogaster (Dmca1A) was determined. Thirty-four exons, distributed over 45 kb of genomic sequence, have been identified and mapped, including exons in three regions involved in alternative splicing and new sites potentially involved in RNA editing. The comparison of the intron/exon boundaries of this channel with a mammalian counterpart shows that the genomic structure of these two genes has remained fairly similar during evolution, with more than half of the Drosophila intron positions being perfectly conserved compared to the human channel. Phylogenetic analysis of the mutually exclusive alternative exons revealed that they have diverged considerably. It is suggested that this divergence, rather than reflecting evolutionary age, is the likely result of accelerated rates of evolution following duplication.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Coleman K. G., Poole S. J., Weir M. P., Soeller W. C., Kornberg T. The invected gene of Drosophila: sequence analysis and expression studies reveal a close kinship to the engrailed gene. Genes Dev. 1987 Mar;1(1):19–28. doi: 10.1101/gad.1.1.19. [DOI] [PubMed] [Google Scholar]
  3. Cowan T. M., Siegel R. W. Drosophila mutations that alter ionic conduction disrupt acquisition and retention of a conditioned odor avoidance response. J Neurogenet. 1986 Jul;3(4):187–201. doi: 10.3109/01677068609106849. [DOI] [PubMed] [Google Scholar]
  4. Coyne J. A. Genetics and speciation. Nature. 1992 Feb 6;355(6360):511–515. doi: 10.1038/355511a0. [DOI] [PubMed] [Google Scholar]
  5. Diebold R. J., Koch W. J., Ellinor P. T., Wang J. J., Muthuchamy M., Wieczorek D. F., Schwartz A. Mutually exclusive exon splicing of the cardiac calcium channel alpha 1 subunit gene generates developmentally regulated isoforms in the rat heart. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1497–1501. doi: 10.1073/pnas.89.4.1497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dunlap K., Luebke J. I., Turner T. J. Exocytotic Ca2+ channels in mammalian central neurons. Trends Neurosci. 1995 Feb;18(2):89–98. [PubMed] [Google Scholar]
  7. Fujita Y., Mynlieff M., Dirksen R. T., Kim M. S., Niidome T., Nakai J., Friedrich T., Iwabe N., Miyata T., Furuichi T. Primary structure and functional expression of the omega-conotoxin-sensitive N-type calcium channel from rabbit brain. Neuron. 1993 Apr;10(4):585–598. doi: 10.1016/0896-6273(93)90162-k. [DOI] [PubMed] [Google Scholar]
  8. George A. L., Jr, Iyer G. S., Kleinfield R., Kallen R. G., Barchi R. L. Genomic organization of the human skeletal muscle sodium channel gene. Genomics. 1993 Mar;15(3):598–606. doi: 10.1006/geno.1993.1113. [DOI] [PubMed] [Google Scholar]
  9. Grabner M., Bachmann A., Rosenthal F., Striessnig J., Schultz C., Tautz D., Glossmann H. Insect calcium channels. Molecular cloning of an alpha 1-subunit from housefly (Musca domestica) muscle. FEBS Lett. 1994 Feb 14;339(1-2):189–194. doi: 10.1016/0014-5793(94)80413-3. [DOI] [PubMed] [Google Scholar]
  10. Hall J. C. The mating of a fly. Science. 1994 Jun 17;264(5166):1702–1714. doi: 10.1126/science.8209251. [DOI] [PubMed] [Google Scholar]
  11. Herb A., Higuchi M., Sprengel R., Seeburg P. H. Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1875–1880. doi: 10.1073/pnas.93.5.1875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Higuchi M., Single F. N., Köhler M., Sommer B., Sprengel R., Seeburg P. H. RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. Cell. 1993 Dec 31;75(7):1361–1370. doi: 10.1016/0092-8674(93)90622-w. [DOI] [PubMed] [Google Scholar]
  13. Hooper J. E., Pérez-Alonso M., Bermingham J. R., Prout M., Rocklein B. A., Wagenbach M., Edstrom J. E., de Frutos R., Scott M. P. Comparative studies of Drosophila Antennapedia genes. Genetics. 1992 Oct;132(2):453–469. doi: 10.1093/genetics/132.2.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Iwabe N., Kuma K., Miyata T. Evolution of gene families and relationship with organismal evolution: rapid divergence of tissue-specific genes in the early evolution of chordates. Mol Biol Evol. 1996 Mar;13(3):483–493. doi: 10.1093/oxfordjournals.molbev.a025609. [DOI] [PubMed] [Google Scholar]
  15. Jan L. Y., Jan Y. N. A superfamily of ion channels. Nature. 1990 Jun 21;345(6277):672–672. doi: 10.1038/345672a0. [DOI] [PubMed] [Google Scholar]
  16. Kamb A., Tseng-Crank J., Tanouye M. A. Multiple products of the Drosophila Shaker gene may contribute to potassium channel diversity. Neuron. 1988 Jul;1(5):421–430. doi: 10.1016/0896-6273(88)90192-4. [DOI] [PubMed] [Google Scholar]
  17. Kyriacou C. P., Hall J. C. Interspecific genetic control of courtship song production and reception in Drosophila. Science. 1986 Apr 25;232(4749):494–497. doi: 10.1126/science.3083506. [DOI] [PubMed] [Google Scholar]
  18. Leicht B. G., Lyckegaard E. M., Benedict C. M., Clark A. G. Conservation of alternative splicing and genomic organization of the myosin alkali light-chain (Mlc1) gene among Drosophila species. Mol Biol Evol. 1993 Jul;10(4):769–790. doi: 10.1093/oxfordjournals.molbev.a040043. [DOI] [PubMed] [Google Scholar]
  19. Lilly M., Kreber R., Ganetzky B., Carlson J. R. Evidence that the Drosophila olfactory mutant smellblind defines a novel class of sodium channel mutation. Genetics. 1994 Mar;136(3):1087–1096. doi: 10.1093/genetics/136.3.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lomeli H., Mosbacher J., Melcher T., Höger T., Geiger J. R., Kuner T., Monyer H., Higuchi M., Bach A., Seeburg P. H. Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science. 1994 Dec 9;266(5191):1709–1713. doi: 10.1126/science.7992055. [DOI] [PubMed] [Google Scholar]
  21. Long M., Rosenberg C., Gilbert W. Intron phase correlations and the evolution of the intron/exon structure of genes. Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12495–12499. doi: 10.1073/pnas.92.26.12495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Loughney K., Kreber R., Ganetzky B. Molecular analysis of the para locus, a sodium channel gene in Drosophila. Cell. 1989 Sep 22;58(6):1143–1154. doi: 10.1016/0092-8674(89)90512-6. [DOI] [PubMed] [Google Scholar]
  23. Melcher T., Maas S., Herb A., Sprengel R., Seeburg P. H., Higuchi M. A mammalian RNA editing enzyme. Nature. 1996 Feb 1;379(6564):460–464. doi: 10.1038/379460a0. [DOI] [PubMed] [Google Scholar]
  24. Mori Y., Friedrich T., Kim M. S., Mikami A., Nakai J., Ruth P., Bosse E., Hofmann F., Flockerzi V., Furuichi T. Primary structure and functional expression from complementary DNA of a brain calcium channel. Nature. 1991 Apr 4;350(6317):398–402. doi: 10.1038/350398a0. [DOI] [PubMed] [Google Scholar]
  25. Mount S. M., Burks C., Hertz G., Stormo G. D., White O., Fields C. Splicing signals in Drosophila: intron size, information content, and consensus sequences. Nucleic Acids Res. 1992 Aug 25;20(16):4255–4262. doi: 10.1093/nar/20.16.4255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nakai J., Adams B. A., Imoto K., Beam K. G. Critical roles of the S3 segment and S3-S4 linker of repeat I in activation of L-type calcium channels. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1014–1018. doi: 10.1073/pnas.91.3.1014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Niidome T., Kim M. S., Friedrich T., Mori Y. Molecular cloning and characterization of a novel calcium channel from rabbit brain. FEBS Lett. 1992 Aug 10;308(1):7–13. doi: 10.1016/0014-5793(92)81038-n. [DOI] [PubMed] [Google Scholar]
  28. Ohta T. Further examples of evolution by gene duplication revealed through DNA sequence comparisons. Genetics. 1994 Dec;138(4):1331–1337. doi: 10.1093/genetics/138.4.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ohta T. Multigene families and the evolution of complexity. J Mol Evol. 1991 Jul;33(1):34–41. doi: 10.1007/BF02100193. [DOI] [PubMed] [Google Scholar]
  30. Reyes A. A., Small S. J., Akeson R. At least 27 alternatively spliced forms of the neural cell adhesion molecule mRNA are expressed during rat heart development. Mol Cell Biol. 1991 Mar;11(3):1654–1661. doi: 10.1128/mcb.11.3.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rueter S. M., Burns C. M., Coode S. A., Mookherjee P., Emeson R. B. Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine. Science. 1995 Mar 10;267(5203):1491–1494. doi: 10.1126/science.7878468. [DOI] [PubMed] [Google Scholar]
  32. Santoni M. J., Barthels D., Vopper G., Boned A., Goridis C., Wille W. Differential exon usage involving an unusual splicing mechanism generates at least eight types of NCAM cDNA in mouse brain. EMBO J. 1989 Feb;8(2):385–392. doi: 10.1002/j.1460-2075.1989.tb03389.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schwarz T. L., Tempel B. L., Papazian D. M., Jan Y. N., Jan L. Y. Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila. Nature. 1988 Jan 14;331(6152):137–142. doi: 10.1038/331137a0. [DOI] [PubMed] [Google Scholar]
  34. Smith L. A., Wang X., Peixoto A. A., Neumann E. K., Hall L. M., Hall J. C. A Drosophila calcium channel alpha1 subunit gene maps to a genetic locus associated with behavioral and visual defects. J Neurosci. 1996 Dec 15;16(24):7868–7879. doi: 10.1523/JNEUROSCI.16-24-07868.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Snutch T. P., Tomlinson W. J., Leonard J. P., Gilbert M. M. Distinct calcium channels are generated by alternative splicing and are differentially expressed in the mammalian CNS. Neuron. 1991 Jul;7(1):45–57. doi: 10.1016/0896-6273(91)90073-9. [DOI] [PubMed] [Google Scholar]
  36. Soldatov N. M. Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4628–4632. doi: 10.1073/pnas.89.10.4628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Stoltzfus A., Spencer D. F., Zuker M., Logsdon J. M., Jr, Doolittle W. F. Testing the exon theory of genes: the evidence from protein structure. Science. 1994 Jul 8;265(5169):202–207. doi: 10.1126/science.8023140. [DOI] [PubMed] [Google Scholar]
  38. Strong M., Chandy K. G., Gutman G. A. Molecular evolution of voltage-sensitive ion channel genes: on the origins of electrical excitability. Mol Biol Evol. 1993 Jan;10(1):221–242. doi: 10.1093/oxfordjournals.molbev.a039986. [DOI] [PubMed] [Google Scholar]
  39. Swimmer C., Fenerjian M. G., Martínez-Cruzado J. C., Kafatos F. C. Evolution of the autosomal chorion cluster in Drosophila. III. Comparison of the s18 gene in evolutionarily distant species and heterospecific control of chorion gene amplification. J Mol Biol. 1990 Sep 20;215(2):225–235. doi: 10.1016/S0022-2836(05)80341-9. [DOI] [PubMed] [Google Scholar]
  40. Tamkun J. W., Deuring R., Scott M. P., Kissinger M., Pattatucci A. M., Kaufman T. C., Kennison J. A. brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell. 1992 Feb 7;68(3):561–572. doi: 10.1016/0092-8674(92)90191-e. [DOI] [PubMed] [Google Scholar]
  41. Thackeray J. R., Ganetzky B. Developmentally regulated alternative splicing generates a complex array of Drosophila para sodium channel isoforms. J Neurosci. 1994 May;14(5 Pt 1):2569–2578. doi: 10.1523/JNEUROSCI.14-05-02569.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wu C. F., Ganetzky B. Neurogenetic studies of ion channels in Drosophila. Ion Channels. 1992;3:261–314. doi: 10.1007/978-1-4615-3328-3_9. [DOI] [PubMed] [Google Scholar]
  44. Zheng W., Feng G., Ren D., Eberl D. F., Hannan F., Dubald M., Hall L. M. Cloning and characterization of a calcium channel alpha 1 subunit from Drosophila melanogaster with similarity to the rat brain type D isoform. J Neurosci. 1995 Feb;15(2):1132–1143. doi: 10.1523/JNEUROSCI.15-02-01132.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES