TBI-Preprint 03-002
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Titel:
Surveying Phylogenetic Footprints in Large Gene Clusters:
Applications to Hox Cluster Duplications
Author(s):
Sonja Prohaska,
Claudia Fried,
Christoph Flamm,
Günter P. Wagner
and Peter F. Stadler
submitted to:
J.Mol.Biol, (2003)
Abstract:
Evolutionarily conserved non-coding genomic sequences represent a
potentially rich source for the discovery of gene regulatory regions. Since
these elements are subject to stabilizing selection they evolve much slower
than adjacent non-functional DNA. These so-called phylogenetic footprints
can be detected by comparison of the sequences surrounding orthologous
genes in different species. In this paper we present a new method and an
efficient software tool for the identification of corresponding footprints
in long sequences from multiple species. This allows the evolutionary study
of the origin and loss of phylogenetic footprints if sufficient number and
appropriately placed species are included. We apply this method to the
published sequences of HoxA clusters of shark, human, and the duplicated
zebrafish and Takifugu clusters as well as the published HoxB cluster
sequences. We find that there is a massive loss of sequence conservation in
the intergenic region of the HoxA clusters, consistent with the finding in
[Chiu et al., PNAS 99, 5492-5497 (2002)]. We further propose a simple model
to estimate the loss of sequence conservation that can be attributed to
gene loss and other structural reasons. We find that the loss of
conservation after cluster duplication is more extensive than expected by
this model. This suggests that binding site turnover and/or adaptive
modification may also contribute to the loss of sequence conservation. We
conclude that this method is suitable for the large scale study of the
evolution of (putative) cis-regulatory elements.
Keywords: Phylogenetic footprints, Hox gene clusters, gene duplication
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