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 certain 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 2 3 Reneker J, Lyons E, Conant GC, Pires JC, Freeling M, Shyu CR, Korkin D (2012). "Long identical multispecies elements in plant and animal genomes". Proceedings of the National Academy of Sciences. 109 (19): E1183–E1191. doi:10.1073/pnas.1121356109. ISSN 0027-8424.
  2. 1 2 3 4 5 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. 1 2 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. 1 2 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 (2011). "Ultraconserved cDNA segments in the human transcriptome exhibit resistance to folding and implicate function in translation and alternative splicing". Nucleic Acids Res. 39 (6): 1967–79. doi:10.1093/nar/gkq949. PMC 3064809Freely accessible. PMID 21062826.
  6. ↑ Taccioli C, Fabbri E, Visone R, Volinia S, Calin GA, Fong LY, Gambari R, Bottoni A, Acunzo M, Hagan J, Iorio MV, Piovan C, Romano G, Croce CM (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 2686429Freely accessible. 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 3021052Freely accessible. PMID 21187392.
  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 526512Freely accessible. PMID 15630479.
  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

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