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. 2001 Oct;159(2):589–598. doi: 10.1093/genetics/159.2.589

The evolutionary analysis of "orphans" from the Drosophila genome identifies rapidly diverging and incorrectly annotated genes.

K J Schmid 1, C F Aquadro 1
PMCID: PMC1461820  PMID: 11606536

Abstract

In genome projects of eukaryotic model organisms, a large number of novel genes of unknown function and evolutionary history ("orphans") are being identified. Since many orphans have no known homologs in distant species, it is unclear whether they are restricted to certain taxa or evolve rapidly, either because of a lack of constraints or positive Darwinian selection. Here we use three criteria for the selection of putatively rapidly evolving genes from a single sequence of Drosophila melanogaster. Thirteen candidate genes were chosen from the Adh region on the second chromosome and 1 from the tip of the X chromosome. We succeeded in obtaining sequence from 6 of these in the closely related species D. simulans and D. yakuba. Only 1 of the 6 genes showed a large number of amino acid replacements and in-frame insertions/deletions. A population survey of this gene suggests that its rapid evolution is due to the fixation of many neutral or nearly neutral mutations. Two other genes showed "normal" levels of divergence between species. Four genes had insertions/deletions that destroy the putative reading frame within exons, suggesting that these exons have been incorrectly annotated. The evolutionary analysis of orphan genes in closely related species is useful for the identification of both rapidly evolving and incorrectly annotated genes.

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Selected References

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  1. Adams M. D., Celniker S. E., Holt R. A., Evans C. A., Gocayne J. D., Amanatides P. G., Scherer S. E., Li P. W., Hoskins R. A., Galle R. F. The genome sequence of Drosophila melanogaster. Science. 2000 Mar 24;287(5461):2185–2195. doi: 10.1126/science.287.5461.2185. [DOI] [PubMed] [Google Scholar]
  2. Akashi H. Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA. Genetics. 1995 Feb;139(2):1067–1076. doi: 10.1093/genetics/139.2.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Akashi H. Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy. Genetics. 1994 Mar;136(3):927–935. doi: 10.1093/genetics/136.3.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Andrews J., Bouffard G. G., Cheadle C., Lü J., Becker K. G., Oliver B. Gene discovery using computational and microarray analysis of transcription in the Drosophila melanogaster testis. Genome Res. 2000 Dec;10(12):2030–2043. doi: 10.1101/gr.10.12.2030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ashburner M., Misra S., Roote J., Lewis S. E., Blazej R., Davis T., Doyle C., Galle R., George R., Harris N. An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. Genetics. 1999 Sep;153(1):179–219. doi: 10.1093/genetics/153.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bauer V. L., Aquadro C. F. Rates of DNA sequence evolution are not sex-biased in Drosophila melanogaster and D. simulans. Mol Biol Evol. 1997 Dec;14(12):1252–1257. doi: 10.1093/oxfordjournals.molbev.a025734. [DOI] [PubMed] [Google Scholar]
  8. Begun D. J., Aquadro C. F. African and North American populations of Drosophila melanogaster are very different at the DNA level. Nature. 1993 Oct 7;365(6446):548–550. doi: 10.1038/365548a0. [DOI] [PubMed] [Google Scholar]
  9. Begun D. J., Whitley P., Todd B. L., Waldrip-Dail H. M., Clark A. G. Molecular population genetics of male accessory gland proteins in Drosophila. Genetics. 2000 Dec;156(4):1879–1888. doi: 10.1093/genetics/156.4.1879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bielawski J. P., Dunn K. A., Yang Z. Rates of nucleotide substitution and mammalian nuclear gene evolution. Approximate and maximum-likelihood methods lead to different conclusions. Genetics. 2000 Nov;156(3):1299–1308. doi: 10.1093/genetics/156.3.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bork P., Dandekar T., Diaz-Lazcoz Y., Eisenhaber F., Huynen M., Yuan Y. Predicting function: from genes to genomes and back. J Mol Biol. 1998 Nov 6;283(4):707–725. doi: 10.1006/jmbi.1998.2144. [DOI] [PubMed] [Google Scholar]
  12. Bork P., Koonin E. V. Predicting functions from protein sequences--where are the bottlenecks? Nat Genet. 1998 Apr;18(4):313–318. doi: 10.1038/ng0498-313. [DOI] [PubMed] [Google Scholar]
  13. Brenner S. E., Chothia C., Hubbard T. J. Population statistics of protein structures: lessons from structural classifications. Curr Opin Struct Biol. 1997 Jun;7(3):369–376. doi: 10.1016/s0959-440x(97)80054-1. [DOI] [PubMed] [Google Scholar]
  14. Brenner S. E. Errors in genome annotation. Trends Genet. 1999 Apr;15(4):132–133. doi: 10.1016/s0168-9525(99)01706-0. [DOI] [PubMed] [Google Scholar]
  15. Burge C., Karlin S. Prediction of complete gene structures in human genomic DNA. J Mol Biol. 1997 Apr 25;268(1):78–94. doi: 10.1006/jmbi.1997.0951. [DOI] [PubMed] [Google Scholar]
  16. Civetta A., Singh R. S. Sex-related genes, directional sexual selection, and speciation. Mol Biol Evol. 1998 Jul;15(7):901–909. doi: 10.1093/oxfordjournals.molbev.a025994. [DOI] [PubMed] [Google Scholar]
  17. Comeron J. M., Kreitman M., Aguadé M. Natural selection on synonymous sites is correlated with gene length and recombination in Drosophila. Genetics. 1999 Jan;151(1):239–249. doi: 10.1093/genetics/151.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Comeron J. M., Kreitman M. The correlation between synonymous and nonsynonymous substitutions in Drosophila: mutation, selection or relaxed constraints? Genetics. 1998 Oct;150(2):767–775. doi: 10.1093/genetics/150.2.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Duda T. F., Jr, Palumbi S. R. Molecular genetics of ecological diversification: duplication and rapid evolution of toxin genes of the venomous gastropod Conus. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6820–6823. doi: 10.1073/pnas.96.12.6820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dunn K. A., Bielawski J. P., Yang Z. Substitution rates in Drosophila nuclear genes: implications for translational selection. Genetics. 2001 Jan;157(1):295–305. doi: 10.1093/genetics/157.1.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Duret L., Mouchiroud D. Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4482–4487. doi: 10.1073/pnas.96.8.4482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Endo T., Ikeo K., Gojobori T. Large-scale search for genes on which positive selection may operate. Mol Biol Evol. 1996 May;13(5):685–690. doi: 10.1093/oxfordjournals.molbev.a025629. [DOI] [PubMed] [Google Scholar]
  23. Ewing B., Hillier L., Wendl M. C., Green P. Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res. 1998 Mar;8(3):175–185. doi: 10.1101/gr.8.3.175. [DOI] [PubMed] [Google Scholar]
  24. Gordon D., Abajian C., Green P. Consed: a graphical tool for sequence finishing. Genome Res. 1998 Mar;8(3):195–202. doi: 10.1101/gr.8.3.195. [DOI] [PubMed] [Google Scholar]
  25. Guigó R., Agarwal P., Abril J. F., Burset M., Fickett J. W. An assessment of gene prediction accuracy in large DNA sequences. Genome Res. 2000 Oct;10(10):1631–1642. doi: 10.1101/gr.122800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hieter P., Boguski M. Functional genomics: it's all how you read it. Science. 1997 Oct 24;278(5338):601–602. doi: 10.1126/science.278.5338.601. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Hurst L. D., Smith N. G. Do essential genes evolve slowly? Curr Biol. 1999 Jul 15;9(14):747–750. doi: 10.1016/s0960-9822(99)80334-0. [DOI] [PubMed] [Google Scholar]
  29. Kliman R. M., Hey J. Reduced natural selection associated with low recombination in Drosophila melanogaster. Mol Biol Evol. 1993 Nov;10(6):1239–1258. doi: 10.1093/oxfordjournals.molbev.a040074. [DOI] [PubMed] [Google Scholar]
  30. Kliman R. M., Hey J. The effects of mutation and natural selection on codon bias in the genes of Drosophila. Genetics. 1994 Aug;137(4):1049–1056. doi: 10.1093/genetics/137.4.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kreitman M., Hudson R. R. Inferring the evolutionary histories of the Adh and Adh-dup loci in Drosophila melanogaster from patterns of polymorphism and divergence. Genetics. 1991 Mar;127(3):565–582. doi: 10.1093/genetics/127.3.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Michelmore R. W., Meyers B. C. Clusters of resistance genes in plants evolve by divergent selection and a birth-and-death process. Genome Res. 1998 Nov;8(11):1113–1130. doi: 10.1101/gr.8.11.1113. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Powell J. R., Moriyama E. N. Evolution of codon usage bias in Drosophila. Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7784–7790. doi: 10.1073/pnas.94.15.7784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Reese M. G., Hartzell G., Harris N. L., Ohler U., Abril J. F., Lewis S. E. Genome annotation assessment in Drosophila melanogaster. Genome Res. 2000 Apr;10(4):483–501. doi: 10.1101/gr.10.4.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. Schmid K. J., Nigro L., Aquadro C. F., Tautz D. Large number of replacement polymorphisms in rapidly evolving genes of Drosophila. Implications for genome-wide surveys of DNA polymorphism. Genetics. 1999 Dec;153(4):1717–1729. doi: 10.1093/genetics/153.4.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schmid K. J., Tautz D. A screen for fast evolving genes from Drosophila. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9746–9750. doi: 10.1073/pnas.94.18.9746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Shields D. C., Sharp P. M., Higgins D. G., Wright F. "Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Mol Biol Evol. 1988 Nov;5(6):704–716. doi: 10.1093/oxfordjournals.molbev.a040525. [DOI] [PubMed] [Google Scholar]
  41. Swanson W. J., Vacquier V. D. Extraordinary divergence and positive Darwinian selection in a fusagenic protein coating the acrosomal process of abalone spermatozoa. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4957–4961. doi: 10.1073/pnas.92.11.4957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. Tautz D., Schmid K. J. From genes to individuals: developmental genes and the generation of the phenotype. Philos Trans R Soc Lond B Biol Sci. 1998 Feb 28;353(1366):231–240. doi: 10.1098/rstb.1998.0205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. 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]
  46. Wright F. The 'effective number of codons' used in a gene. Gene. 1990 Mar 1;87(1):23–29. doi: 10.1016/0378-1119(90)90491-9. [DOI] [PubMed] [Google Scholar]
  47. Wyckoff G. J., Wang W., Wu C. I. Rapid evolution of male reproductive genes in the descent of man. Nature. 2000 Jan 20;403(6767):304–309. doi: 10.1038/35002070. [DOI] [PubMed] [Google Scholar]
  48. Yang Z., Nielsen R., Goldman N., Pedersen A. M. Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics. 2000 May;155(1):431–449. doi: 10.1093/genetics/155.1.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yokoyama S., Zhang H., Radlwimmer F. B., Blow N. S. Adaptive evolution of color vision of the Comoran coelacanth (Latimeria chalumnae). Proc Natl Acad Sci U S A. 1999 May 25;96(11):6279–6284. doi: 10.1073/pnas.96.11.6279. [DOI] [PMC free article] [PubMed] [Google Scholar]

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