Skip to main content
SpringerLink
Log in

Evolution of cis-Regulatory Sequences in Drosophila

  • Protocol
  • First Online:
Computational Biology of Transcription Factor Binding

Part of the book series: Methods in Molecular Biology ((MIMB,volume 674))

  • 3885 Accesses

Abstract

Cross-species comparison is an emerging paradigm for identifying cis-regulatory sequences and understanding their function and evolution. In this chapter, we review probabilistic models of evolution of transcription factor binding sites, which provide the theoretical basis for a number of new bioinformatics tools for comparative sequence analysis. We illustrate how important functional and evolutionary insights on binding site gain and loss can be acquired through sequence comparison. This includes the observation that binding site turnover follows a molecular clock and that its rate correlates with the strength of binding sites and the presence of other sites in the neighborhood. We also comment on emerging trends that go beyond individual binding sites to a more holistic study of regulatory evolution. We point out common technical challenges, such as reliable sequence alignment and binding site prediction, when doing comparative regulatory sequence analysis and note some potential solutions thereof.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Howard, M.L., and Davidson, E.H. (2004) cis-Regulatory control circuits in development. Dev Biol 271, 109–118.

    Article  PubMed  CAS  Google Scholar 

  2. Papatsenko, D., and Levine, M. (2005) Computational identification of regulatory DNAs underlying animal development. Nat Methods 2, 529–534.

    Article  PubMed  CAS  Google Scholar 

  3. GuhaThakurta, D. (2006) Computational identification of transcriptional regulatory elements in DNA sequence. Nucleic Acids Res 34, 3585–3598.

    Article  PubMed  CAS  Google Scholar 

  4. Stark, A., Lin, M.F., Kheradpour, P. et al. (2007) Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures. Nature 450, 219–232.

    Article  PubMed  CAS  Google Scholar 

  5. Wray, G.A., Hahn, M.W., Abouheif, E. et al. (2003) The evolution of transcriptional regulation in eukaryotes. Mol Biol Evol 20, 1377–1419.

    Article  PubMed  CAS  Google Scholar 

  6. Wittkopp, P.J. (2006) Evolution of cis-regulatory sequence and function in Diptera. Heredity 97, 139–147.

    Article  PubMed  CAS  Google Scholar 

  7. Carroll, S., Grenier, J., and Weatherbee, S. (2001) From DNA to diversity: molecular genetics and the evolution of animal design. Blackwell Science, Oxford.

    Google Scholar 

  8. Stormo, G.D. (2000) DNA binding sites: representation and discovery. Bioinformatics 16, 16–23.

    Article  PubMed  CAS  Google Scholar 

  9. Schneider, T.D., and Stephens, R.M. (1990) Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 18, 6097–6100.

    Article  PubMed  CAS  Google Scholar 

  10. Sharon, E., Lubliner, S., and Segal, E. (2008) A feature-based approach to modeling protein-DNA interactions. PLoS Comput Biol 4, e1000154.

    Article  PubMed  Google Scholar 

  11. Loots, G. G., and Ovcharenko, I. (2004) rVISTA 2.0: evolutionary analysis of transcription factor binding sites. Nucleic Acids Res 32, W217–221.

    Article  PubMed  CAS  Google Scholar 

  12. Wasserman, W.W., Palumbo, M., Thompson, W. et al. (2000) Human-mouse genome comparisons to locate regulatory sites. Nat Genet 26, 225–228.

    Article  PubMed  CAS  Google Scholar 

  13. Doniger, S.W., Huh, J., and Fay, J.C. (2005) Identification of functional transcription factor binding sites using closely related Saccharomyces species. Genome Res 15, 701–709.

    Article  PubMed  CAS  Google Scholar 

  14. Dermitzakis, E.T., Bergman, C.M., and Clark, A.G. (2003) Tracing the evolutionary history of Drosophila regulatory regions with models that identify transcription factor binding sites. Mol Biol Evol 20, 703–714.

    Article  PubMed  CAS  Google Scholar 

  15. Ludwig, M.Z., Patel, N.H., and Kreitman, M. (1998) Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change. Development 125, 949–958.

    PubMed  CAS  Google Scholar 

  16. Doniger, S.W., and Fay, J.C. (2007) Frequent gain and loss of functional transcription factor binding sites. PLoS Comput Biol 3, e99.

    Article  PubMed  Google Scholar 

  17. Borneman, A.R., Gianoulis, T.A., Zhang, Z.D. et al. (2007) Divergence of transcription factor binding sites across related yeast species. Science 317, 815–819.

    Article  PubMed  CAS  Google Scholar 

  18. Moses, A.M., Pollard, D.A., Nix, D.A. et al. (2006) Large-scale turnover of functional transcription factor binding sites in Drosophila. PLoS Comput Biol 2, e130.

    Article  PubMed  Google Scholar 

  19. Yang, Z. (2006) Computational Molecular Evolution. Oxford University Press.

    Google Scholar 

  20. Miklos, I., Novak, A., Satija, R., Lingso, R., and Hein, J. (2009) Stochastic models of sequence evolution including insertion-deletion events. Stat Methods Med Res 18(5), 453–485.

    Article  PubMed  Google Scholar 

  21. Felsenstein, J. (1981) Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol 17, 368–376.

    Article  PubMed  CAS  Google Scholar 

  22. Sinha, S., van Nimwegen, E., and Siggia, E.D. (2003) A probabilistic method to detect regulatory modules. Bioinformatics 19(Suppl. 1), i292–i301.

    Article  PubMed  Google Scholar 

  23. Siddharthan, R., Siggia, E.D., and van Nimwegen, E. (2005) PhyloGibbs: a Gibbs sampling motif finder that incorporates phylogeny. PLoS Comput Biol 1, e67.

    Article  PubMed  Google Scholar 

  24. Hasegawa, M., Kishino, H., and Yano, T. (1985) Dating of the human-ape splitting by a molecular clock of mitochondrial DNA. J Mol Evol 22, 160–174.

    Article  PubMed  CAS  Google Scholar 

  25. Halpern, A.L., and Bruno, W.J. (1998) Evolutionary distances for protein-coding sequences: modeling site-specific residue frequencies. Mol Biol Evol 15, 910–917.

    Article  PubMed  CAS  Google Scholar 

  26. Kimura, M. (1983) The neutral theory of molecular evolution, Cambridge University Press, Cambridge, MA.

    Book  Google Scholar 

  27. Crow, J.F., and Kimura, M. (1970) An introduction to population genetics theory. Harper & Row Publishers, New York, NY.

    Google Scholar 

  28. Moses, A.M., Chiang, D.Y., Kellis, M. et al. (2003) Position specific variation in the rate of evolution in transcription factor binding sites. BMC Evol Biol 3, 19.

    Article  PubMed  Google Scholar 

  29. Kim, J., He, X., and Sinha, S. (2009) Evolution of regulatory sequences in 12 Drosophila species. PLoS Genet 5, e1000330.

    Article  PubMed  Google Scholar 

  30. Hartl, D.L., and Clark, A.G. (2006) Principles of poulation genetics. Sinauer Associates, Sunderland, MA.

    Google Scholar 

  31. Berg, J., Willmann, S., and Lassig, M. (2004) Adaptive evolution of transcription factor binding sites. BMC Evol Biol 4, 42.

    Article  PubMed  Google Scholar 

  32. Mustonen, V., and Lässig, M. (2005) Evolutionary population genetics of promoters: predicting binding sites and functional phylogenies. Proc Natl Acad Sci USA 102, 15936–15941.

    Article  PubMed  CAS  Google Scholar 

  33. Mustonen, V., Kinney, J., Callan, C.G., Jr., and Lassig, M. (2008) Energy-dependent fitness: a quantitative model for the evolution of yeast transcription factor binding sites. Proc Natl Acad Sci USA 105, 12376–12381.

    Article  PubMed  CAS  Google Scholar 

  34. Raijman, D., Shamir, R., and Tanay, A. (2008) Evolution and selection in yeast promoters: analyzing the combined effect of diverse transcription factor binding sites. PLoS Comput Biol 4, e7.

    Article  PubMed  Google Scholar 

  35. Stormo, G.D., and Fields, D.S. (1998) Specificity, free energy and information content in protein-DNA interactions. Trends Biochem Sci 23, 109–113.

    Article  PubMed  CAS  Google Scholar 

  36. Ludwig, M.Z. (2002) Functional evolution of noncoding DNA. Curr Opin Genet Dev 12, 634–639.

    Article  PubMed  CAS  Google Scholar 

  37. Papatsenko, D., and Levine, M. (2005) Quantitative analysis of binding motifs mediating diverse spatial readouts of the Dorsal gradient in the Drosophila embryo. Proc Natl Acad Sci USA 102, 4966–4971.

    Article  PubMed  CAS  Google Scholar 

  38. Struhl, K. (2001) Gene regulation. A paradigm for precision. Science 293, 1054–1055.

    Article  PubMed  CAS  Google Scholar 

  39. Gray, S., and Levine, M. (1996) Transcriptional repression in development. Curr Opin Cell Biol 8, 358–364.

    Article  PubMed  CAS  Google Scholar 

  40. Hare, E.E., Peterson, B.K., Iyer, V.N., Meier, R., and Eisen, M.B. (2008) Sepsid even-skipped enhancers are functionally conserved in Drosophila despite lack of sequence conservation. PLoS Genet 4, e1000106.

    Article  PubMed  Google Scholar 

  41. Small, S., Blair, A., and Levine, M. (1992) Regulation of even-skipped stripe 2 in the Drosophila embryo. EMBO J 11, 4047–4057.

    PubMed  CAS  Google Scholar 

  42. Kulkarni, M.M., and Arnosti, D.N. (2005) cis-regulatory logic of short-range transcriptional repression in Drosophila melanogaster. Mol Cell Biol 25, 3411–3420.

    Article  PubMed  CAS  Google Scholar 

  43. Huang, W., Nevins, J.R., and Ohler, U. (2007) Phylogenetic simulation of promoter evolution: estimation and modeling of binding site turnover events and assessment of their impact on alignment tools. Genome Biol 8, R225.

    Article  PubMed  Google Scholar 

  44. MacArthur, S., and Brookfield, J.F. (2004) Expected rates and modes of evolution of enhancer sequences. Mol Biol Evol 21, 1064–1073.

    Article  PubMed  CAS  Google Scholar 

  45. Khatri, B.S., McLeish, T. C., and Sear, R. P. (2009) Statistical mechanics of convergent evolution in spatial patterning. Proc Natl Acad Sci USA 106, 9564–9569.

    Article  PubMed  CAS  Google Scholar 

  46. Wong, K.M., Suchard, M.A., and Huelsenbeck, J.P. (2008) Alignment uncertainty and genomic analysis. Science 319, 473–476.

    Article  PubMed  CAS  Google Scholar 

  47. Berezikov, E., Guryev, V., Plasterk, R.H., and Cuppen, E. (2004) CONREAL: conserved regulatory elements anchored alignment algorithm for identification of transcription factor binding sites by phylogenetic footprinting. Genome Res 14, 170–178.

    Article  PubMed  CAS  Google Scholar 

  48. Hallikas, O., Palin, K., Sinjushina, N. et al. (2006) Genome-wide prediction of mammalian enhancers based on analysis of transcription factor binding affinity. Cell 124, 47–59.

    Article  PubMed  CAS  Google Scholar 

  49. Bais, A.S., Grossmann, S., and Vingron, M. (2007) Simultaneous alignment and annotation of cis-regulatory regions. Bioinformatics 23, e44–e49.

    Article  PubMed  CAS  Google Scholar 

  50. Sinha, S., and He, X. (2007) MORPH: probabilistic alignment combined with hidden Markov models of cis-regulatory modules. PLoS Comput Biol 3, e216.

    Article  PubMed  Google Scholar 

  51. He, X., Ling, X., and Sinha, S. (2009) Alignment and prediction of cis-regulatory modules based on a probabilistic model of evolution. PLoS Comput Biol 5, e1000299.

    Article  PubMed  Google Scholar 

  52. Do, C.B., Mahabhashyam, M.S., Brudno, M., and Batzoglou, S. (2005) ProbCons: probabilistic consistency-based multiple sequence alignment. Genome Res 15, 330–340.

    Article  PubMed  CAS  Google Scholar 

  53. Tanay, A., Regev, A., and Shamir, R. (2005) Conservation and evolvability in regulatory networks: the evolution of ribosomal regulation in yeast. Proc Natl Acad Sci USA 102, 7203–7208.

    Article  PubMed  CAS  Google Scholar 

  54. Sinha, S., Schroeder, M.D., Unnerstall, U. et al. (2004) Cross-species comparison significantly improves genome-wide prediction of cis-regulatory modules in Drosophila. BMC Bioinformatics 5, 129.

    Article  PubMed  Google Scholar 

  55. Bulyk, M.L. (2006) DNA microarray technologies for measuring protein-DNA interactions. Curr Opin Biotechnol 17, 422–430.

    Article  PubMed  CAS  Google Scholar 

  56. Barski, A., and Zhao, K. (2009) Genomic location analysis by ChIP-Seq. J Cell Biochem 107, 11–18.

    Article  PubMed  CAS  Google Scholar 

  57. Moses, A.M., Chiang, D.Y., Pollard, D.A. et al. (2004) MONKEY: identifying conserved transcription-factor binding sites in multiple alignments using a binding site-specific evolutionary model. Genome Biol 5, R98.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    Xin He & Saurabh Sinha

Authors
  1. Xin He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saurabh Sinha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Saurabh Sinha .

Editor information

Editors and Affiliations

  1. , Department of Statistics, University of Nebraska-Lincoln, Vine Street 1901, Lincoln, 68588-0665, Nebraska, USA

    Istvan Ladunga

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

He, X., Sinha, S. (2010). Evolution of cis-Regulatory Sequences in Drosophila . In: Ladunga, I. (eds) Computational Biology of Transcription Factor Binding. Methods in Molecular Biology, vol 674. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-854-6_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-854-6_18

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-853-9

  • Online ISBN: 978-1-60761-854-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation