Evolutionarily Conserved Noncoding DNA

The availability of increasingly complete and accurate genomic sequence data from evolutionarily separated species – as well as diverse strains and ethnic variants within species – is providing an unprecedented opportunity to identify potentially functional regions within genomic noncoding deoxyribonucleic acid (DNA). A variety of bioinformatics tools enable genome-wide detection, characterization and visualization of highly conserved sequences and the occurrence of potentially functional elements within both the conserved and evolved elements.

Keywords: phylogenetic conservation; Noncoding DNA; regulatory region; cis-elements; promoter; enhancer

 References
    Aerts S, Van Loo P, Thijs G et al. (2005) TOUCAN 2: the all-inclusive open source workbench for regulatory sequence analysis. Nucleic Acids Research 33(Web Server issue): W393–W396.
    Ansari-Lari MA, Oeltjen JC, Schwartz S et al. (1998) Comparative sequence analysis of a gene-rich cluster at human chromosome 12p13 and its syntenic region in mouse chromosome 6. Genome Research 8(1): 29–40.
    Balakirev ES and Ayala FJ (2003) Pseudogenes: are they “junk” or functional DNA? Annual Review of Genetics 37: 123–151.
    Bejerano G, Pheasant M, Makunin I et al. (2004) Ultraconserved elements in the human genome. Science 304(5675): 1321–1325.
    Birney E, Stamatoyannopoulos JA, Dutta A et al. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447(7146): 799–816.
    Blanchette M and Tompa M (2003) FootPrinter: a program designed for phylogenetic footprinting. Nucleic Acids Research 31(13): 3840–3842.
    Brickner AG, Koop BF, Aronow BJ and Wiginton DA (1999) Genomic sequence comparison of the human and mouse adenosine deaminase gene regions. Mammalian Genome 10(2): 95–101.
    book Cooper DN (1999) Human Gene Evolution. Oxford: BIOS Scientific.
    Cunningham JM, Purucker ME, Jane SM et al. (1994) The regulatory element 3¢ to the A gamma-globin gene binds to the nuclear matrix and interacts with special A-T-rich binding protein 1 (SATB1), an SAR/MAR-associating region DNA binding protein. Blood 84(4): 1298–1308.
    van Deursen D, Botma GJ, Jansen H and Verhoeven AJ (2007) Comparative genomics and experimental promoter analysis reveal functional liver-specific elements in mammalian hepatic lipase genes. BMC Genomics 8: 99.
    Duret L, Dorkeld F and Gautier C (1993) Strong conservation of non-coding sequences during vertebrates evolution: potential involvement in post-transcriptional regulation of gene expression. Nucleic Acids Research 21(10): 2315–2322.
    Flint J, Tufarelli C, Peden J et al. (2001) Comparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the alpha globin cluster. Human Molecular Genetics 10(4): 371–382.
    Frith MC, Pheasant M and Mattick JS (2005) The amazing complexity of the human transcriptome. European Journal of Human Genetics 13(8): 894–897.
    Greaves DR, Quinn CM, Seldin MF and Gordon S (1998) Functional comparison of the murine macrosialin and human CD68 promoters in macrophage and nonmacrophage cell lines. Genomics 54(1): 165–168.
    Gumucio DL, Shelton DA, Zhu W et al. (1996) Evolutionary strategies for the elucidation of cis and trans factors that regulate the developmental switching programs of the beta-like globin genes. Molecular Phylogenetics and Evolution 5(1): 18–32.
    Hood L, Rowen L and Koop BF (1995) Human and mouse T-cell receptor loci: genomics, evolution, diversity, and serendipity. Annals of the New York Academy of Sciences 758: 390–412.
    Jareborg N, Birney E and Durbin R (1999) Comparative analysis of noncoding regions of 77 orthologous mouse and human gene pairs. Genome Research 9(9): 815–824.
    Jeffares DC, Mourier T and Penny D (2006) The biology of intron gain and loss. Trends in Genetics 22(1): 16–22.
    Jegga AG, Chen J, Gowrisankar S et al. (2007) GenomeTrafac: a whole genome resource for the detection of transcription factor binding site clusters associated with conventional and microRNA encoding genes conserved between mouse and human gene orthologs. Nucleic Acids Research 35(Database issue): D116–D121.
    Jegga AG, Sherwood SP, Carman JW et al. (2002) Detection and visualization of compositionally similar cis-regulatory element clusters in orthologous and coordinately controlled genes. Genome Research 12(9): 1408–1417.
    Jurka J, Zietkiewicz E and Labuda D (1995) Ubiquitous mammalian-wide interspersed repeats (MIRs) are molecular fossils from the mesozoic era. Nucleic Acids Research 23(1): 170–175.
    Katzman S, Kern AD, Bejerano G et al. (2007) Human genome ultraconserved elements are ultraselected. Science 317(5840): 915.
    Loots GG, Ovcharenko I, Pachter L, Dubchak I and Rubin EM (2002) rVista for comparative sequence-based discovery of functional transcription factor binding sites. Genome Research 12(5): 832–839.
    Makalowski W, Zhang J and Boguski MS (1996) Comparative analysis of 1196 orthologous mouse and human full-length mRNA and protein sequences. Genome Research 6(9): 846–857.
    Marchese A, Cheng R, Lee MC et al. (1994) Mapping studies of two G protein-coupled receptor genes: an amino acid difference may confer a functional variation between a human and rodent receptor. Biochemical and Biophysical Research Communications 205(3): 1952–1958.
    Margarit E, Guillen A, Rebordosa C et al. (1998) Identification of conserved potentially regulatory sequences of the SRY gene from 10 different species of mammals. Biochemical and Biophysical Research Communications 245(2): 370–377.
    Mattick JS and Makunin IV (2006) Non-coding RNA. Human Molecular Genetics 15(Spec No 1): R17–29.
    Mazumder B, Seshadri V and Fox PL (2003) Translational control by the 3¢-UTR: the ends specify the means. Trends in Biochemical Sciences 28(2): 91–98.
    Mikkelsen TS, Wakefield MJ, Aken B et al. (2007) Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. Nature 447(7141): 167–177.
    Nobrega MA, Zhu Y, Plajzer-Frick I, Afzal V and Rubin EM (2004) Megabase deletions of gene deserts result in viable mice. Nature 431(7011): 988–993.
    Oeltjen JC, Malley TM, Muzny DM et al. (1997) Large-scale comparative sequence analysis of the human and murine Bruton's tyrosine kinase loci reveals conserved regulatory domains. Genome Research 7(4): 315–329.
    Olsen PH and Ambros V (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental Biology 216(2): 671–680.
    Pang KC, Frith MC and Mattick JS (2006) Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends in Genetics 22(1): 1–5.
    Plotnikova OV, Kondrashov FA, Vlasov PK et al. (2007) Conversion and compensatory evolution of the gamma-crystallin genes and identification of a cataractogenic mutation that reverses the sequence of the human CRYGD gene to an ancestral state. American Journal of Human Genetics 81(1): 32–43.
    Ponting CP and Lunter G (2006) Signatures of adaptive evolution within human non-coding sequence. Human Molecular Genetics 15(Spec No 2): R170–R175.
    Ravetch JV, Kirsch IR and Leder P (1980) Evolutionary approach to the question of immunoglobulin heavy chain switching: evidence from cloned human and mouse genes. Proceedings of the National Academy of Sciences of the USA 77(11): 6734–6738.
    Sandelin A, Wasserman WW and Lenhard B (2004) ConSite: web-based prediction of regulatory elements using cross-species comparison. Nucleic Acids Research 32(Web Server issue): W249–W252.
    Smit AF and Riggs AD (1995) MIRs are classic, tRNA-derived SINEs that amplified before the mammalian radiation. Nucleic Acids Research 23(1): 98–102.
    Stallings RL (1995) Conservation and evolution of (CT)n/(GA)n microsatellite sequences at orthologous positions in diverse mammalian genomes. Genomics 25(1): 107–113.
    Vargas-Madrazo E, Almagro JC and Lara-Ochoa F (1995) Structural repertoire in VH pseudogenes of immunoglobulins: comparison with human germline genes and human amino acid sequences. Journal of Molecular Biology 246(1): 74–81.
    Ward RD, Davis SW, Cho M et al. (2007) Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene. Mammalian Genome 18(6–7): 521–537.
 Further Reading
    Clark MS (1999) Comparative genomics: the key to understanding the human genome project. BioEssays 21: 121–130.
    Ludwig MZ (2002) Functional evolution of noncoding DNA. Current Opinion in Genetics & Development 12: 634–639.
    Miller W, Makova KD, Nekrutenko A and Hardison RC (2004) Comparative genomics. Annual Review of Genomics and Human Genetics 5: 15–56.
    Stone EA, Cooper GM and Sidow A (2005) Trade-offs in detecting evolutionarily constrained sequence by comparative genomics. Annual Review of Genomics and Human Genetics 6: 143–164.
 Web Links
    ePath glucose phosphate isomerase (GPI); Entrez Gene ID: 2821. Entrez Gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&list_uids=2821.
    ePath glucose phosphate isomerase (GPI); MIM number: 172400. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?172400.
    ePath hemoglobin, A (HBG1); Entrez Gene ID: 3047. Entrez Gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&list_uids=3047.
    ePath hemoglobin, A (HBG1); MIM number: 142200. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?142200.
    ePath RNA, 7SL, cytoplasmic (RN7SL); Entrez Gene ID: 6029. Entrez Gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&list_uids=6029.
    ePath tyrosine hydroxylase (TH); Entrez Gene ID: 7054. Entrez Gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&list_uids=7054.
    ePath tyrosine hydroxylase (TH); MIM number: 191290. OMIM: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191290.
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How to Cite close
Jegga, Anil G, and Aronow, Bruce J(May 2008) Evolutionarily Conserved Noncoding DNA. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006126.pub2]