4/22/2005
1:00pm-2:00pm
LIBR M549
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Using Evolution to Explore the Human Genome
University of California, Santa Cruz
The reference sequence of the human genome was recently produced, along with
drafts of the chimp, mouse, rat, dog, cow, chicken and other genomes.
Data and analysis of these is available on the
UCSC Genome Bioinformatics
genome browser,
a site that now averages more than 5,000 different users per day. The site
currently features an interactive "microscope" on the human genome and its
evolution, via cross-species comparative genomics.
Sequence comparison reveals that at least 5% of the human genome is under
negative selection. Negative selection occurs in important functional segments
of the genome where random (mostly deleterious) mutations are rejected by
natural selection, leaving the orthologous segments in different species more
similar than would be expected under a neutral substitution model. Protein
coding regions account for only about 1/3 of the segments that are under
negative selection. In fact, the most conserved segments of the human genome do
not appear to code for protein. These "ultraconserved" elements, of length from
200-800bp, are totally unchanged between human mouse and rat, and are on
average 96% identical in chicken. The function of most is currently unknown,
but there is evidence that many may be distal enhancers controlling the
expression of genes involved in embryonic development.
We are also investigating genetic innovations that are specific to primates or
specific to humans. These occur through positive selection of advantageous
changes. Via simulation, we estimate that most of the DNA sequence of the
common ancestor of all placental mammals, which lived in the last part
Cretaceous period about 80 million years ago, can be predicted with 98%
accuracy. Given this as a base, and enough well-placed primate genomes to
reconstruct intermediate states, we should eventually be able to document most
of the genomic changes that occurred in the evolution of the human lineage from
the mammalian ancestor over the last 80 million years, including innovations
that arose by positive selection.
This talk will be held in the Norlin Library British and Irish Studies Room.
Haussler will also present a Mervyn Young Memorial Lecture later in the day.
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