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Comparing the human, mouse and rat genomes: Prof. David Haussler
The reference sequence of the human genome was recently produced, along with drafts of
the mouse and rat genomes. Data and bioinformatic analysis of these is available on the
genome browser at
http://genome.ucsc.edu,
a site that is now receiving more than
140,000 page requests per day. We'll tell a bit of the history of this site, which was where
the first publicly accessible working draft of the human genome was posted. Then we'll
discuss comparative genomic methods to predict functional elements in these genomes,
used in some of the analysis presented at that site. A statistical estimate based on a simple
measure of conservation between short orthologous segments in the human and mouse
genomes suggests (very roughly) that about 5% of the human genome shows signs of
being under Darwinian selection (in particular, purifying selection), but does not
definitively tell us which segments are under selection. We are using new models of
molecular evolution to address this question. These models include context dependencies
between substitutions at adjacent bases and allow for different rates of evolution in
different parts of the chromosomes, as has been confirmed in recent analysis. These are
being used to find regions of the human genome that are evolving like coding exons in
genes, and occasionally lead to the prediction of a new human gene. Deeper analysis
using genome data from 12 vertebrates in the region of the human cystic fibrosis gene has
also allowed us to pinpoint a host of previously unexplored non-coding conserved
elements in the human genome. Determining the function of these elements poses an
intriguing problem. Finally, we'll look at the large scale rearrangements that have
happened in the evolution of the human and mouse genomes, in an analysis that reveals
chromosomal rearrangement "hotspots".
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