Ultraconserved DNA Sequence Elements in the Human Genome

Alison P Lee, Institute of Molecular and Cell Biology, Biopolis, Singapore
B Venkatesh, Institute of Molecular and Cell Biology, Biopolis, Singapore

Published online: May 2008

DOI: 10.1002/9780470015902.a0020842

Ultraconserved elements are deoxyribonucleic acid (DNA) sequences at least 200 base pairs in length and perfectly conserved in human, mouse and rat genomes. These elements are under extreme purifying selection and are implicated in functions such as transcriptional enhancers, exons of noncoding ribonucleic acid (RNA) transcripts and alternatively spliced ‘poison cassette exons’ that regulate the expression of certain classes of proteins.

Keywords: ultraconserved element; human genome; purifying selection; transcriptional enhancer

Figure 1. Alignment of a representative ultraconserved element (uc.123, bold line above alignment) in human (H), mouse (M), rat (R), dog (D), chicken (C) and fugu (F). This element is located in the intergenic region of FNDC6 and SOX14. Shaded nucleotides indicate the consensus base of each alignment column.
Figure 2. Ultraconserved elements that flank (a) DACH1 and (b) Iroquois genes act as distal transcriptional enhancers. The alignments include sequences from human/mouse/rat (H/M/R), dog (D), chicken (C) and fugu (F). The ultraconserved elements shown are a subregion of the corresponding enhancer that was validated in transgenic mice (DACH1) or Xenopus (IrxB cluster) assays. Not drawn to scale.
Figure 3. Multiplexing of two functions onto a single ultraconserved element. Ultraconserved element uc.221 is an ultraconserved transcriptional enhancer (ei) and also encodes a noncoding RNA that acts as a coactivator of the Dlx2 transcription factor. Enhancers ei and eii are marked by shaded boxes, while exons of noncoding RNA Evf-1 and Evf-2 are shown by unshaded boxes. The two alternative transcripts of Evf are shown in solid and dotted lines.
Figure 4. Unproductive splicing of SR genes SFRS3 and SFRS1. Ultraconserved elements (bold lines above exons) may overlap (a) ‘poison cassette exons’ that contain a premature termination codon (star symbol) or (b) cryptic 3¢ UTR introns. Two different splice variants are shown (solid and dotted lines) that connect the exons of each gene. In (b), the normal stop codon is marked with a circle. Not drawn to scale.
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    Poulin F, Nobrega MA, Plajzer-Frick I et al. (2005) In vivo characterization of a vertebrate ultraconserved enhancer. Genomics 85: 774–781.
    Sandelin A, Bailey P, Bruce S et al. (2004) Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes. BMC Genomics 5: 99.
    Siepel A, Bejerano G, Pedersen JS et al. (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Research 15: 1034–1050.

Related Sub-Topics:

Evolutionary Genomics | Molecular Evolution | Selection and Variation | Human Evolution | Evolution of Coding and Functional Modules
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Article Title: Ultraconserved DNA Sequence Elements in the Human Genome
 
How to Cite close
Lee, Alison P, and Venkatesh, B(May 2008) Ultraconserved DNA Sequence Elements in the Human Genome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020842]