Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants

Nature Genetics volume 38, pages 1216–1220 (2006)Cite this article

Abstract

An earlier search in the human, mouse and rat genomes for sequences that are 100% conserved in orthologous segments and ≥200 bp in length identified 481 distinct sequences1. These human-mouse-rat sequences, which represent ultraconserved elements (UCEs), are believed to be important for functions involving DNA binding, RNA processing and the regulation of transcription and development. In vivo and additional computational studies of UCEs and other highly conserved sequences are consistent with these functional associations, with some observations indicating enhancer-like activity for these elements1,2,3,4,5,6,7,8,9. Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants. Notably, of the UCEs that are found in segmental duplications or copy number variants, the majority overlap exons, indicating, along with other findings presented, that UCEs overlapping exons represent a distinct subset.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: UCEs, segmental duplications (SD) and CNVs.
Figure 2: Genomic features on chromosome 17.
Figure 3: Mammalian UCEs are depleted among segmental duplications.

Similar content being viewed by others

References

  1. Bejerano, G. et al. Ultraconserved elements in the human genome. Science 304, 1321–1325 (2004).

    Article  CAS  Google Scholar 

  2. Boffelli, D. et al. Phylogenetic shadowing of primate sequences to find functional regions of the human genome. Science 299, 1391–1394 (2003).

    Article  CAS  Google Scholar 

  3. Nobrega, M.A., Ovcharenko, I., Afzal, V. & Rubin, E.M. Scanning human gene deserts for long-range enhancers. Science 302, 413 (2003).

    Article  CAS  Google Scholar 

  4. Sandelin, A. et al. Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes. BMC Genomics 5, 99 (2004).

    Article  Google Scholar 

  5. Woolfe, A. et al. Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol. 3, e7 (2005).

    Article  Google Scholar 

  6. Poulin, F. et al. In vivo characterization of a vertebrate ultraconserved enhancer. Genomics 85, 774–781 (2005).

    Article  CAS  Google Scholar 

  7. de la Calle-Mustienes, E. et al. A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts. Genome Res. 15, 1061–1072 (2005).

    Article  CAS  Google Scholar 

  8. Goode, D.K., Snell, P., Smith, S.F., Cooke, J.E. & Elgar, G. Highly conserved regulatory elements around the SHH gene may contribute to the maintenance of conserved synteny across human chromosome 7q36.3. Genomics 86, 172–181 (2005).

    Article  CAS  Google Scholar 

  9. Bejerano, G. et al. A distal enhancer and an ultraconserved exon are derived from a novel retroposon. Nature 441, 87–90 (2006).

    Article  CAS  Google Scholar 

  10. Bailey, J.A. et al. Recent segmental duplications in the human genome. Science 297, 1003–1007 (2002).

    Article  CAS  Google Scholar 

  11. Bailey, J.A., Liu, G. & Eichler, E.E. An Alu transposition model for the origin and expansion of human segmental duplications. Am. J. Hum. Genet. 73, 823–834 (2003).

    Article  CAS  Google Scholar 

  12. Cheung, J. et al. Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence. Genome Biol. 4, R25 (2003).

    Article  Google Scholar 

  13. Cheung, J. et al. Recent segmental and gene duplications in the mouse genome. Genome Biol. 4, R47 (2003).

    Article  Google Scholar 

  14. She, X. et al. Shotgun sequence assembly and recent segmental duplications within the human genome. Nature 431, 927–930 (2004).

    Article  CAS  Google Scholar 

  15. Tuzun, E. et al. Fine-scale structural variation of the human genome. Nat. Genet. 37, 727–732 (2005).

    Article  CAS  Google Scholar 

  16. Sebat, J. et al. Large-scale copy number polymorphism in the human genome. Science 305, 525–528 (2004).

    Article  CAS  Google Scholar 

  17. Iafrate, A.J. et al. Detection of large-scale variation in the human genome. Nat. Genet. 36, 949–951 (2004).

    Article  CAS  Google Scholar 

  18. Sharp, A.J. et al. Segmental duplications and copy-number variation in the human genome. Am. J. Hum. Genet. 77, 78–88 (2005).

    Article  CAS  Google Scholar 

  19. Hinds, D.A., Kloek, A.P., Jen, M., Chen, X. & Frazer, K.A. Common deletions and SNPs are in linkage disequilibrium in the human genome. Nat. Genet. 38, 82–85 (2006).

    Article  CAS  Google Scholar 

  20. Conrad, D.F., Andrews, T.D., Carter, N.P., Hurles, M.E. & Pritchard, J.K. A high-resolution survey of deletion polymorphism in the human genome. Nat. Genet. 38, 75–81 (2006).

    Article  CAS  Google Scholar 

  21. McCarroll, S.A. et al. Common deletion polymorphisms in the human genome. Nat. Genet. 38, 86–92 (2006).

    Article  CAS  Google Scholar 

  22. Feuk, L., Carson, A.R. & Scherer, S.W. Structural variation in the human genome. Nat. Rev. Genet. 7, 85–97 (2006).

    Article  CAS  Google Scholar 

  23. Eichler, E.E. Widening the spectrum of human genetic variation. Nat. Genet. 38, 9–11 (2006).

    Article  CAS  Google Scholar 

  24. ICGSC. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432, 695–716 (2004).

  25. Siepel, A. et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034–1050 (2005).

    Article  CAS  Google Scholar 

  26. Dermitzakis, E.T. et al. Comparison of human chromosome 21 conserved nongenic sequences (CNGs) with the mouse and dog genomes shows that their selective constraint is independent of their genic environment. Genome Res. 14, 852–859 (2004).

    Article  CAS  Google Scholar 

  27. Duncan, I.W. Transvection effects in Drosophila. Annu. Rev. Genet. 36, 521–556 (2002).

    Article  CAS  Google Scholar 

  28. Kennison, J.A. & Southworth, J.W. Transvection in Drosophila. Adv. Genet. 46, 399–420 (2002).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank D. Haussler, G. Bejerano and M. Nobrega for valuable discussions; P. Green for introducing C.-t.W. to UCEs and suggesting they may pair; J. Aach, A. Dudley, H. Malik, S. Otto, J. Seidman, I. Yanai, members of the Church, Roth and Wu laboratories and attendees of the 2005 Epigenetics GRC for comments and ideas and D. Gurgul, Partners Research Computing at Massachusetts General Hospital, and the West Quad Computing Group and Research Information Technology Group at Harvard Medical School for computational resources. This work was supported by the Keck Foundation and by US National Institutes of Health (NIH) grants HG0017115 and HG003224 (F.P.R. and A.D.), by the NIH Centers of Excellence in Genomic Science (G.M.C. and A.D.) and by NIH grant GM61936 and HMS (C.-t.W. and A.D.).

Author information

Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Adnan Derti & Frederick P Roth

  2. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Adnan Derti & George M Church

  3. Lipper Center for Computational Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Adnan Derti & George M Church

  4. Bioinformatics Program, Boston University, Boston, 02215, Massachusetts, USA

    Adnan Derti

  5. Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USA

    Frederick P Roth

  6. Divisions of Genetics and Molecular Medicine, Harvard Medical School, Boston, 02115, Massachusetts, USA

    C-ting Wu

Authors
  1. Adnan Derti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frederick P Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George M Church
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C-ting Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C-ting Wu.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Human genome map of UCEs and other features. (PDF 123 kb)

Supplementary Fig. 2

Overlaps of exon types for exonic UCEs. (PDF 111 kb)

Supplementary Fig. 3

Best matches to the intronic and intergenictr UCEs exhibit lower overall percentage identity as compared to matches to the exonic UCEs. (PDF 163 kb)

Supplementary Table 1

Intronic and intergenictr (but not exonic) UCEs are depleted among SDs and CNVs. (PDF 97 kb)

Supplementary Table 2

Overlap of combined UCEs with exons. (PDF 105 kb)

Supplementary Table 3

UCE sequences and genomic coordinates of all sequence elements. (XLS 2533 kb)

Supplementary Methods (PDF 121 kb)

Supplementary Note (PDF 260 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Derti, A., Roth, F., Church, G. et al. Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants. Nat Genet 38, 1216–1220 (2006). https://doi.org/10.1038/ng1888

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1888

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing