Bioinformatics Preprint 06-001
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Titel:
Genome-Wide Analysis of Single Nucleotide Polymorphisms in
Evolutionary Conserved DNA
Author(s):
Claudia Fried,
Peter F. Stadler,
Peter Ahnert
Submitted
Genome Research
Abstract:
Variation databases promise to enable the assessment of recent selection
pressure on genomic sequence elements. Evidence of recent selection would
suggest recent functional relevance of elements potentially important for
understanding the organization of the human genome and resulting complex
phenotypes and diseases. In contrast, comparative sequence analysis can be
employed to focus on those regions that have have been under long-term
stabilizing selection. Previously observed biases in variation databases
appear to have been reduced to the point that their data can now be used to
for investigate the relationships of long-term sequence preservation and
recent selective pressures.
In a genome-wide study, we identified phylogenetic footprints (PFs) in the
vicinity of human genes. In agreement with the distribution of known
regulatory sites, the density of these PFs was highest within two thousand
base pairs upstream and downstream of genes. Stabilizing selection acting
on these PFs was most strongly indicated by significantly reduced single
nucleotide polymorphism (SNP) density. Weak correlation between SNP
densities of PFs and coding sequences suggests that gene regulation and
function often evolve independently. Decreasing diversity in human genes
with increasing time of conservation suggests that most old genes have not
ceased to be functionally important today. On average, intergenic sequences
are under the least selection pressure in the vicinity of genes and may
serve as a preferred model for estimating neutral evolution.
Intriguingly, we observed increased SNP densities in coding sequences and
introns as compared to non-coding sequences of genes conserved only among
primates. These genes appear to be mainly involved in the regulation of
gene expression and raise the question about mechanisms for adaptive
evolution and their role in primate development.
Keywords: Sequence Homology, Nucleic Acid, Evolution, Phylogeny, Single Nucleotide Polymorphism, Genome, Transcription Factors, Gene Expression Regulation
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