You and the fugu, part 2

My earlier post introduced the conserved noncoding elements shared by vertebrates. Those elements shared by vertebrates seem to be crucial to regulating developmental genes, and are not found in any invertebrates. Now a current paper by Tanya Vavouri and colleagues reports that other conserved noncoding elements have evolved in parallel in worms.

I'm posting it because it gives another good mini-introduction to these conserved seqeunces in vertebrates:

Comparisons of the human genome against the genomes of distantly related vertebrates have revealed an abundance of highly conserved non-coding elements (CNEs) that appear to have been 'frozen' throughout vertebrate evolution [1-7]. The exact number of elements shared between any set of species varies depending on the precise definition of similarity and the divergence of the genomes used. For example, a comparison of the human genome against the mouse and the rat genomes revealed that all three share 256 elements with no evidence of transcription that are 100% identical over at least 200 base-pairs (bp) [2]. Furthermore, the human genome and the genome of the Japanese pufferfish (Fugu rubripes), which diverged from a common ancestor approximately 450 million years ago (MYA), share 1,373 CNEs, with an average length of 199 bp and average identity of 84% [4].
A striking property of human CNEs is that they cluster in genomic regions that contain genes coding for transcription factors and signaling genes involved in the regulation of development ('trans-dev' genes) [2-4,6]. Therefore, CNEs have been proposed to act as cis-regulatory sequences for these trans-dev genes. In support of this, where tested, the majority of assayed CNEs can act as tissue-specific enhancers for a transgene in zebrafish or mice [4,7-10].

So it looks like the first ten references in the paper are an essential group to review in terms of outlining the regulation of vertebrate developmental genes. I've pasted them in below; it's a field that has originated largely within the last three years.


Vavouri T, Walter K, Gilks WR, Lehner B, Elgar G. 2007. Parallel evolution of conserved non-coding elements that target a common set of developmental regulatory genes from worms to humans. Genome Biology 8:R15. doi:10.1186/gb-2007-8-2-r15

1. Boffelli D, Nobrega MA, Rubin EM: Comparative genomics at the vertebrate extremes. Nat Rev Genet 2004, 5:456-465.

2. Bejerano G, Pheasant M, Makunin I, Stephen S, Kent WJ, Mattick JS, Haussler D: Ultraconserved elements in the human genome. Science 2004, 304:1321-1325.

3. Sandelin A, Bailey P, Bruce S, Engstrom PG, Klos JM, Wasserman WW, Ericson J, Lenhard B: Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes. BMC Genomics 2004, 5:99.

4. Woolfe A, Goodson M, Goode DK, Snell P, McEwen GK, Vavouri T, Smith SF, North P, Callaway H, Kelly K, et al.: Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol 2005, 3:e7.

5. Dermitzakis ET, Reymond A, Antonarakis SE: Conserved non-genic sequences - an unexpected feature of mammalian genomes. Nat Rev Genet 2005, 6:151-157.

6. Vavouri T, McEwen GK, Woolfe A, Gilks WR, Elgar G: Defining a genomic radius for long-range enhancer action: duplicated conserved non-coding elements hold the key. Trends Genet 2006, 22:5-10.

7. McEwen GK, Woolfe A, Goode D, Vavouri T, Callaway H, Elgar G: Ancient duplicated conserved noncoding elements in vertebrates: a genomic and functional analysis. Genome Res 2006, 16:451-465.

8. Nobrega MA, Ovcharenko I, Afzal V, Rubin EM: Scanning human gene deserts for long-range enhancers.
Science 2003, 302:413.

9. de la Calle-Mustienes E, Feijoo CG, Manzanares M, Tena JJ, Rodriguez-Seguel E, Letizia A, Allende ML, Gomez-Skarmeta JL: A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts. Genome Res 2005, 15:1061-1072.

10. Goode DK, Snell P, Smith SF, Cooke JE, Elgar G: Highly conserved regulatory elements around the SHH gene may contribute to the maintenance of conserved synteny across human chromosome 7q36.3. Genomics 2005, 86:172-181.