Ultra-conserved element

An ultra-conserved element (UCE) is a region of DNA that is identical in at least two different species.[1] One of the first studies of UCEs showed that human DNA sequences of length 200 nucleotides or greater were entirely conserved (identical nucleic acid sequence) in both rats and mice.[2] Despite often being noncoding DNA,[3] some ultra-conserved elements have been found to be transcriptionally active, giving non-coding RNA molecules.[4]

Evolution

Perfect conservation of these long stretches of DNA is thought to imply evolutionary importance as these regions appear to have experienced strong negative selection for 300-400 million years.[2][3][5] The probability of finding ultra-conserved elements by chance (under neutral evolution) has been estimated at less than 10−22 in 2.9 billion bases.[2]

Functions

481 ultra-conserved elements have been identified in the human genome.[1][2] A database collecting genomic information about ultra-conserved elements (UCbase) that share 100% identity among human, mouse and rat is available at http://ucbase.unimore.it.[6] A small number of those which are transcribed have been connected with human carcinomas and leukemias.[4] For example, TUC338 is strongly upregulated in human hepatocellular carcinoma cells.[7] A study comparing ultra-conserved elements between humans and Takifugu rubripes proposed an importance in vertebrate development.[8] Several ultra-conserved elements are located near transcriptional regulators or developmental genes.[2][9] Other functions include enhancing and splicing regulation.[1]

See also

References

  1. ↑ 1.0 1.1 1.2 Reneker, Jeff; Eric Lyons, Gavin C. Conant, J. Chris Pires, Michael Freeling, Chi-Ren Shyu and Dmitry Korkin (2012-05-08). "Long identical multispecies elements in plant and animal genomes". PNAS 109 (19): 1183–1191. doi:10.1073/pnas.1121356109.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Bejerano, G; Pheasant, M; Makunin, I; Stephen, S; Kent, WJ; Mattick, JS; Haussler, D (2004-05-28). "Ultraconserved elements in the human genome.". Science 304 (5675): 1321–5. doi:10.1126/science.1098119. PMID 15131266.
  3. ↑ 3.0 3.1 Katzman, S; Kern, AD, Bejerano, G, Fewell, G, Fulton, L, Wilson, RK, Salama, SR, Haussler, D (2007-08-17). "Human genome ultraconserved elements are ultraselected.". Science 317 (5840): 915. doi:10.1126/science.1142430. PMID 17702936.
  4. ↑ 4.0 4.1 Calin, GA; Liu, CG, Ferracin, M, Hyslop, T, Spizzo, R, Sevignani, C, Fabbri, M, Cimmino, A, Lee, EJ, Wojcik, SE, Shimizu, M, Tili, E, Rossi, S, Taccioli, C, Pichiorri, F, Liu, X, Zupo, S, Herlea, V, Gramantieri, L, Lanza, G, Alder, H, Rassenti, L, Volinia, S, Schmittgen, TD, Kipps, TJ, Negrini, M, Croce, CM (Sep 2007). "Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas.". Cancer Cell 12 (3): 215–29. doi:10.1016/j.ccr.2007.07.027. PMID 17785203.
  5. ↑ Sathirapongsasuti, JF; Sathira, N; Suzuki, Y; Huttenhower, C; Sugano, S (Mar 2011). "Ultraconserved cDNA segments in the human transcriptome exhibit resistance to folding and implicate function in translation and alternative splicing.". Nucleic Acids Research 39 (6): 1967–79. doi:10.1093/nar/gkq949. PMC 3064809. PMID 21062826. Retrieved 17 August 2011.
  6. ↑ Taccioli, Cristian; Fabbri Enrica, Visone Rosa, Volinia Stefano, Calin George A, Fong Louise Y, Gambari Roberto, Bottoni Arianna, Acunzo Mario, Hagan John, Iorio Marilena V, Piovan Claudia, Romano Giulia, Croce Carlo Maria (Jan 2009). "UCbase & miRfunc: a database of ultraconserved sequences and microRNA function". Nucleic Acids Res. 37 (Database issue): D41–8. doi:10.1093/nar/gkn702. PMC 2686429. PMID 18945703.
  7. ↑ Braconi, C; Valeri, N; Kogure, T; Gasparini, P; Huang, N; Nuovo, GJ; Terracciano, L; Croce, CM; Patel, T (2011-01-11). "Expression and functional role of a transcribed noncoding RNA with an ultraconserved element in hepatocellular carcinoma.". Proceedings of the National Academy of Sciences of the United States of America 108 (2): 786–91. doi:10.1073/pnas.1011098108. PMC 3021052. PMID 21187392. Retrieved 18 August 2011.
  8. ↑ Woolfe, A; Goodson, M, Goode, DK, Snell, P, McEwen, GK, Vavouri, T, Smith, SF, North, P, Callaway, H, Kelly, K, Walter, K, Abnizova, I, Gilks, W, Edwards, YJ, Cooke, JE, Elgar, G (Jan 2005). "Highly conserved non-coding sequences are associated with vertebrate development.". PLoS Biology 3 (1): e7. doi:10.1371/journal.pbio.0030007. PMC 526512. PMID 15630479. Retrieved 18 August 2011.
  9. ↑ "Unexpressed but Indispensable—The DNA Sequences That Control Development". PLoS Biology 3 (1): e19. Jan 2005. doi:10.1371/journal.pbio.0030019.

Ryu et al. BMC Evolutionary Biology 2012 http://www.biomedcentral.com/1471-2148/12/236