Ultra-conserved element

An ultra-conserved element is a region of human DNA of length 200 nucleotides or greater, which is entirely conserved (identical nucleic acid sequence) in both rats and mice.[1] Despite often being noncoding DNA,[2] some ultra-conserved elements have been found to be transcriptionally active, giving non-coding RNA molecules.[3]

Contents

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.[1][2][4] 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.[1]

Functions

481 ultra-conserved elements have been identified in the human genome.[1] A small number of those which are transcribed have been connected with human carcinomas and leukemias.[3] For example, TUC338 is strongly upregulated in human hepatocellular carcinoma cells.[5] A study comparing ultra-conserved elements between humans and Fugu rubripes proposed an importance in vertebrate development.[6] Several ultra-conserved elements are located near transcriptional regulators or developmental genes.[1][7]

See also

References

  1. ^ a b c d e 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. 
  2. ^ a b 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. 
  3. ^ a b 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 (2007 Sep). "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. 
  4. ^ Sathirapongsasuti, JF; Sathira, N, Suzuki, Y, Huttenhower, C, Sugano, S (2011 Mar). "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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3064809. Retrieved 17 August 2011. 
  5. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3021052. Retrieved 18 August 2011. 
  6. ^ 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 (2005 Jan). "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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=526512. Retrieved 18 August 2011. 
  7. ^ "Unexpressed but Indispensable—The DNA Sequences That Control Development". PLoS Biology 3 (1): e19. Jan 2005. doi:10.1371/journal.pbio.0030019.