Research
Comparative genomics using Fugu reveals insights into regulatory subfunctionalization
Adam Woolfe1 ,2 and Greg Elgar1
1School of Biological Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
2Genomic Functional Analysis Section, National Human Genome Research Institute, National Institutes of Health, Rockville, MD 20870, USA
Background
A major mechanism for the preservation of gene duplicates in the genome is thought to be mediated via loss or modification of cis-regulatory subfunctions between paralogs following duplication (a process known as regulatory subfunctionalization). Despite a number of gene expression studies that support this mechanism, no comprehensive analysis of regulatory subfunctionalization has been undertaken at the level of the distal cis-regulatory modules involved. We have exploited fish-mammal genomic alignments to identify and compare more than 800 conserved non-coding elements (CNEs) that associate with genes that have undergone fish-specific duplication and retention.
Results
Using the abundance of duplicated genes within the Fugu genome, we selected seven pairs of teleost-specific paralogs involved in early vertebrate development, each containing clusters of CNEs in their vicinity. CNEs present around each Fugu duplicated gene were identified using multiple alignments of orthologous regions between single-copy mammalian orthologs (representing the ancestral locus) and each fish duplicated region in turn. Comparative analysis reveals a pattern of element retention and loss between paralogs indicative of subfunctionalization, the extent of which differs between duplicate pairs. In addition to complete loss of specific regulatory elements, a number of CNEs have been retained in both regions but may be responsible for more subtle levels of subfunctionalization through sequence divergence.
Conclusion
Comparative analysis of conserved elements between duplicated genes provides a powerful approach for studying regulatory subfunctionalization at the level of the regulatory elements involved.
Subject areas: Evolution, Genome studies
Genome Biology 2007, 8:R53. This is an open access article distributed under the terms of the Creative Commons Attribution License.
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