Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2004 Jul;167(3):1199–1212. doi: 10.1534/genetics.104.026252

Nucleotide variation in the Egfr locus of Drosophila melanogaster.

Arnar Palsson 1, Ann Rouse 1, Rebecca Riley-Berger 1, Ian Dworkin 1, Greg Gibson 1
PMCID: PMC1470963  PMID: 15280235

Abstract

The Epidermal growth factor receptor is an essential gene with diverse pleiotropic roles in development throughout the animal kingdom. Analysis of sequence diversity in 10.9 kb covering the complete coding region and 6.4 kb of potential regulatory regions in a sample of 250 alleles from three populations of Drosophila melanogaster suggests that the intensity of different population genetic forces varies along the locus. A total of 238 independent common SNPs and 20 indel polymorphisms were detected, with just six common replacements affecting >1475 amino acids, four of which are in the short alternate first exon. Sequence diversity is lowest in a 2-kb portion of intron 2, which is also highly conserved in comparison with D. simulans and D. pseudoobscura. Linkage disequilibrium decays to background levels within 500 bp of most sites, so haplotypes are generally restricted to up to 5 polymorphisms. The two North American samples from North Carolina and California have diverged in allele frequency at a handful of individual SNPs, but a Kenyan sample is both more divergent and more polymorphic. The effect of sample size on inference of the roles of population structure, uneven recombination, and weak selection in patterning nucleotide variation in the locus is discussed.

Full Text

The Full Text of this article is available as a PDF (362.5 KB).

Selected References

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

  1. Andolfatto P., Przeworski M. A genome-wide departure from the standard neutral model in natural populations of Drosophila. Genetics. 2000 Sep;156(1):257–268. doi: 10.1093/genetics/156.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andolfatto Peter, Wall Jeffrey D. Linkage disequilibrium patterns across a recombination gradient in African Drosophila melanogaster. Genetics. 2003 Nov;165(3):1289–1305. doi: 10.1093/genetics/165.3.1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aquadro C. F., Bauer DuMont V., Reed F. A. Genome-wide variation in the human and fruitfly: a comparison. Curr Opin Genet Dev. 2001 Dec;11(6):627–634. doi: 10.1016/s0959-437x(00)00245-8. [DOI] [PubMed] [Google Scholar]
  4. Ardlie Kristin G., Kruglyak Leonid, Seielstad Mark. Patterns of linkage disequilibrium in the human genome. Nat Rev Genet. 2002 Apr;3(4):299–309. doi: 10.1038/nrg777. [DOI] [PubMed] [Google Scholar]
  5. Berry A., Kreitman M. Molecular analysis of an allozyme cline: alcohol dehydrogenase in Drosophila melanogaster on the east coast of North America. Genetics. 1993 Jul;134(3):869–893. doi: 10.1093/genetics/134.3.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bustamante Carlos D., Nielsen Rasmus, Sawyer Stanley A., Olsen Kenneth M., Purugganan Michael D., Hartl Daniel L. The cost of inbreeding in Arabidopsis. Nature. 2002 Apr 4;416(6880):531–534. doi: 10.1038/416531a. [DOI] [PubMed] [Google Scholar]
  7. Caracristi G., Schlötterer C. Genetic differentiation between American and European Drosophila melanogaster populations could be attributed to admixture of African alleles. Mol Biol Evol. 2003 Apr 2;20(5):792–799. doi: 10.1093/molbev/msg091. [DOI] [PubMed] [Google Scholar]
  8. Clifford R., Schüpbach T. Molecular analysis of the Drosophila EGF receptor homolog reveals that several genetically defined classes of alleles cluster in subdomains of the receptor protein. Genetics. 1994 Jun;137(2):531–550. doi: 10.1093/genetics/137.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Duchek P., Rørth P. Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis. Science. 2001 Jan 5;291(5501):131–133. doi: 10.1126/science.291.5501.131. [DOI] [PubMed] [Google Scholar]
  10. Dworkin Ian, Palsson Arnar, Birdsall Kelli, Gibson Greg. Evidence that Egfr contributes to cryptic genetic variation for photoreceptor determination in natural populations of Drosophila melanogaster. Curr Biol. 2003 Oct 28;13(21):1888–1893. doi: 10.1016/j.cub.2003.10.001. [DOI] [PubMed] [Google Scholar]
  11. Fay J. C., Wu C. I. Hitchhiking under positive Darwinian selection. Genetics. 2000 Jul;155(3):1405–1413. doi: 10.1093/genetics/155.3.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fraser Hunter B., Hirsh Aaron E., Steinmetz Lars M., Scharfe Curt, Feldman Marcus W. Evolutionary rate in the protein interaction network. Science. 2002 Apr 26;296(5568):750–752. doi: 10.1126/science.1068696. [DOI] [PubMed] [Google Scholar]
  13. Freeman M. Complexity of EGF receptor signalling revealed in Drosophila. Curr Opin Genet Dev. 1998 Aug;8(4):407–411. doi: 10.1016/s0959-437x(98)80110-x. [DOI] [PubMed] [Google Scholar]
  14. Frydenberg J., Hoffmann A. A., Loeschcke V. DNA sequence variation and latitudinal associations in hsp23, hsp26 and hsp27 from natural populations of Drosophila melanogaster. Mol Ecol. 2003 Aug;12(8):2025–2032. doi: 10.1046/j.1365-294x.2002.01882.x. [DOI] [PubMed] [Google Scholar]
  15. Fu Y. X., Li W. H. Statistical tests of neutrality of mutations. Genetics. 1993 Mar;133(3):693–709. doi: 10.1093/genetics/133.3.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Galindo M. I., Bishop S. A., Greig S., Couso J. P. Leg patterning driven by proximal-distal interactions and EGFR signaling. Science. 2002 Jul 12;297(5579):256–259. doi: 10.1126/science.1072311. [DOI] [PubMed] [Google Scholar]
  17. Gasperini R., Gibson G. Absence of protein polymorphism in the Ras genes of Drosophila melanogaster. J Mol Evol. 1999 Nov;49(5):583–590. doi: 10.1007/pl00006579. [DOI] [PubMed] [Google Scholar]
  18. Gellon G., McGinnis W. Shaping animal body plans in development and evolution by modulation of Hox expression patterns. Bioessays. 1998 Feb;20(2):116–125. doi: 10.1002/(SICI)1521-1878(199802)20:2<116::AID-BIES4>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  19. Glinka Sascha, Ometto Lino, Mousset Sylvain, Stephan Wolfgang, De Lorenzo David. Demography and natural selection have shaped genetic variation in Drosophila melanogaster: a multi-locus approach. Genetics. 2003 Nov;165(3):1269–1278. doi: 10.1093/genetics/165.3.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hudson R. R., Kreitman M., Aguadé M. A test of neutral molecular evolution based on nucleotide data. Genetics. 1987 May;116(1):153–159. doi: 10.1093/genetics/116.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Johnson Hamlet M. R., Perkins L. A. Analysis of corkscrew signaling in the Drosophila epidermal growth factor receptor pathway during myogenesis. Genetics. 2001 Nov;159(3):1073–1087. doi: 10.1093/genetics/159.3.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kirby D. A., Stephan W. Multi-locus selection and the structure of variation at the white gene of Drosophila melanogaster. Genetics. 1996 Oct;144(2):635–645. doi: 10.1093/genetics/144.2.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Langley C. H., Lazzaro B. P., Phillips W., Heikkinen E., Braverman J. M. Linkage disequilibria and the site frequency spectra in the su(s) and su(w(a)) regions of the Drosophila melanogaster X chromosome. Genetics. 2000 Dec;156(4):1837–1852. doi: 10.1093/genetics/156.4.1837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lesokhin A. M., Yu S. Y., Katz J., Baker N. E. Several levels of EGF receptor signaling during photoreceptor specification in wild-type, Ellipse, and null mutant Drosophila. Dev Biol. 1999 Jan 1;205(1):129–144. doi: 10.1006/dbio.1998.9121. [DOI] [PubMed] [Google Scholar]
  25. Lev Z., Shilo B. Z., Kimchie Z. Developmental changes in expression of the Drosophila melanogaster epidermal growth factor receptor gene. Dev Biol. 1985 Aug;110(2):499–502. doi: 10.1016/0012-1606(85)90107-1. [DOI] [PubMed] [Google Scholar]
  26. Lewontin R C. The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. Genetics. 1964 Jan;49(1):49–67. doi: 10.1093/genetics/49.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lewontin R. C. On measures of gametic disequilibrium. Genetics. 1988 Nov;120(3):849–852. doi: 10.1093/genetics/120.3.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mayor C., Brudno M., Schwartz J. R., Poliakov A., Rubin E. M., Frazer K. A., Pachter L. S., Dubchak I. VISTA : visualizing global DNA sequence alignments of arbitrary length. Bioinformatics. 2000 Nov;16(11):1046–1047. doi: 10.1093/bioinformatics/16.11.1046. [DOI] [PubMed] [Google Scholar]
  29. McDonald J. H., Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature. 1991 Jun 20;351(6328):652–654. doi: 10.1038/351652a0. [DOI] [PubMed] [Google Scholar]
  30. Moriyama E. N., Powell J. R. Intraspecific nuclear DNA variation in Drosophila. Mol Biol Evol. 1996 Jan;13(1):261–277. doi: 10.1093/oxfordjournals.molbev.a025563. [DOI] [PubMed] [Google Scholar]
  31. Nijhout H. F. The nature of robustness in development. Bioessays. 2002 Jun;24(6):553–563. doi: 10.1002/bies.10093. [DOI] [PubMed] [Google Scholar]
  32. Olsen Kenneth M., Womack Andrew, Garrett Ashley R., Suddith Jane I., Purugganan Michael D. Contrasting evolutionary forces in the Arabidopsis thaliana floral developmental pathway. Genetics. 2002 Apr;160(4):1641–1650. doi: 10.1093/genetics/160.4.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Petrov D. A., Hartl D. L. High rate of DNA loss in the Drosophila melanogaster and Drosophila virilis species groups. Mol Biol Evol. 1998 Mar;15(3):293–302. doi: 10.1093/oxfordjournals.molbev.a025926. [DOI] [PubMed] [Google Scholar]
  34. Pritchard J. K., Stephens M., Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000 Jun;155(2):945–959. doi: 10.1093/genetics/155.2.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Reich D. E., Cargill M., Bolk S., Ireland J., Sabeti P. C., Richter D. J., Lavery T., Kouyoumjian R., Farhadian S. F., Ward R. Linkage disequilibrium in the human genome. Nature. 2001 May 10;411(6834):199–204. doi: 10.1038/35075590. [DOI] [PubMed] [Google Scholar]
  36. Richter B., Long M., Lewontin R. C., Nitasaka E. Nucleotide variation and conservation at the dpp locus, a gene controlling early development in Drosophila. Genetics. 1997 Feb;145(2):311–323. doi: 10.1093/genetics/145.2.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Riley Rebecca M., Jin Wei, Gibson Greg. Contrasting selection pressures on components of the Ras-mediated signal transduction pathway in Drosophila. Mol Ecol. 2003 May;12(5):1315–1323. doi: 10.1046/j.1365-294x.2003.01741.x. [DOI] [PubMed] [Google Scholar]
  38. Rosenberg Noah A., Pritchard Jonathan K., Weber James L., Cann Howard M., Kidd Kenneth K., Zhivotovsky Lev A., Feldman Marcus W. Genetic structure of human populations. Science. 2002 Dec 20;298(5602):2381–2385. doi: 10.1126/science.1078311. [DOI] [PubMed] [Google Scholar]
  39. Rozas J., Rozas R. DnaSP version 3: an integrated program for molecular population genetics and molecular evolution analysis. Bioinformatics. 1999 Feb;15(2):174–175. doi: 10.1093/bioinformatics/15.2.174. [DOI] [PubMed] [Google Scholar]
  40. Schaeffer S. W., Miller E. L. Estimates of linkage disequilibrium and the recombination parameter determined from segregating nucleotide sites in the alcohol dehydrogenase region of Drosophila pseudoobscura. Genetics. 1993 Oct;135(2):541–552. doi: 10.1093/genetics/135.2.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schejter E. D., Segal D., Glazer L., Shilo B. Z. Alternative 5' exons and tissue-specific expression of the Drosophila EGF receptor homolog transcripts. Cell. 1986 Sep 26;46(7):1091–1101. doi: 10.1016/0092-8674(86)90709-9. [DOI] [PubMed] [Google Scholar]
  42. Schlötterer Christian, Harr Bettina. Single nucleotide polymorphisms derived from ancestral populations show no evidence for biased diversity estimates in Drosophila melanogaster. Mol Ecol. 2002 May;11(5):947–950. doi: 10.1046/j.1365-294x.2002.01491.x. [DOI] [PubMed] [Google Scholar]
  43. Shilo Ben Zion. Signaling by the Drosophila epidermal growth factor receptor pathway during development. Exp Cell Res. 2003 Mar 10;284(1):140–149. doi: 10.1016/s0014-4827(02)00094-0. [DOI] [PubMed] [Google Scholar]
  44. Simonsen K. L., Churchill G. A., Aquadro C. F. Properties of statistical tests of neutrality for DNA polymorphism data. Genetics. 1995 Sep;141(1):413–429. doi: 10.1093/genetics/141.1.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Stein R. A., Staros J. V. Evolutionary analysis of the ErbB receptor and ligand families. J Mol Evol. 2000 May;50(5):397–412. doi: 10.1007/s002390010043. [DOI] [PubMed] [Google Scholar]
  46. Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. doi: 10.1093/genetics/123.3.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Teeter K., Naeemuddin M., Gasperini R., Zimmerman E., White K. P., Hoskins R., Gibson G. Haplotype dimorphism in a SNP collection from Drosophila melanogaster. J Exp Zool. 2000 Apr 15;288(1):63–75. doi: 10.1002/(sici)1097-010x(20000415)288:1<63::aid-jez7>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. Verrelli B. C., Eanes W. F. Clinal variation for amino acid polymorphisms at the Pgm locus in Drosophila melanogaster. Genetics. 2001 Apr;157(4):1649–1663. doi: 10.1093/genetics/157.4.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wall J. D. Insights from linked single nucleotide polymorphisms: what we can learn from linkage disequilibrium. Curr Opin Genet Dev. 2001 Dec;11(6):647–651. doi: 10.1016/s0959-437x(00)00248-3. [DOI] [PubMed] [Google Scholar]
  51. Wall Jeffrey D., Andolfatto Peter, Przeworski Molly. Testing models of selection and demography in Drosophila simulans. Genetics. 2002 Sep;162(1):203–216. doi: 10.1093/genetics/162.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Wang S. H., Simcox A., Campbell G. Dual role for Drosophila epidermal growth factor receptor signaling in early wing disc development. Genes Dev. 2000 Sep 15;14(18):2271–2276. doi: 10.1101/gad.827000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Watterson G. A. On the number of segregating sites in genetical models without recombination. Theor Popul Biol. 1975 Apr;7(2):256–276. doi: 10.1016/0040-5809(75)90020-9. [DOI] [PubMed] [Google Scholar]
  54. Waxman D., Peck J. R. Pleiotropy and the preservation of perfection. Science. 1998 Feb 20;279(5354):1210–1213. [PubMed] [Google Scholar]
  55. Weir B. S., Hill W. G. Estimating F-statistics. Annu Rev Genet. 2002 Jun 11;36:721–750. doi: 10.1146/annurev.genet.36.050802.093940. [DOI] [PubMed] [Google Scholar]
  56. Wu C. I., Hollocher H., Begun D. J., Aquadro C. F., Xu Y., Wu M. L. Sexual isolation in Drosophila melanogaster: a possible case of incipient speciation. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2519–2523. doi: 10.1073/pnas.92.7.2519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Yang Hsiao-Pei, Nuzhdin Sergey V. Fitness costs of Doc expression are insufficient to stabilize its copy number in Drosophila melanogaster. Mol Biol Evol. 2003 Apr 2;20(5):800–804. doi: 10.1093/molbev/msg087. [DOI] [PubMed] [Google Scholar]
  58. Yang Lihui, Baker Nicholas E. Cell cycle withdrawal, progression, and cell survival regulation by EGFR and its effectors in the differentiating Drosophila eye. Dev Cell. 2003 Mar;4(3):359–369. doi: 10.1016/s1534-5807(03)00059-5. [DOI] [PubMed] [Google Scholar]
  59. Zecca Myriam, Struhl Gary. Control of growth and patterning of the Drosophila wing imaginal disc by EGFR-mediated signaling. Development. 2002 Mar;129(6):1369–1376. doi: 10.1242/dev.129.6.1369. [DOI] [PubMed] [Google Scholar]
  60. Zurovcová Martina, Ayala Francisco J. Polymorphism patterns in two tightly linked developmental genes, Idgf1 and Idgf3, of Drosophila melanogaster. Genetics. 2002 Sep;162(1):177–188. doi: 10.1093/genetics/162.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES