Insights from Comparative Genomics: From Genome Organization to Regulatory Complexity

Speaker: Jeff Chuang , Boston College
Date: October 3 2005
Time: 11:30AM to 1:00PM
Location: TOC Lab 32-G575
Host: P Clote, BC & B Berger. MIT
Contact: Kathleen Dickey, 617 253 3037, kvdickey@mit.edu
Relevant URL: http://www-math.mit.edu/compbiosem/The neutral mutation rate is known to vary widely along human chromosomes,
leading to mutational hot and cold regions. We provide evidence that categories
of functionally related genes reside preferentially in mutationally hot or cold
regions, the size of which we have measured. Our results show that genes are
located nonrandomly with respect to hot and cold regions, offering the possibility
that selection acts at the level of gene location in the human genome. In contrast
to the heterogeneity of mammals, we find that neutral mutation rates in yeast are
uniform genome-wide. We develop an approach that uses this uniform rate to
estimate the amount of promoter sequence under purifying selection. This
amount is ~30%, corresponding to roughly 90 bp for a typical promoter.
Furthermore, using a hidden Markov model, we are able to separate each
promoter into distinct high and low conservation regions. The separation of
functionally conserved sequence from the neutral background allows us to
estimate the complexity of yeast cis-regulation on a genomic scale.
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