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Colloquium - Haussler

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.

Department of Computer Science
University of Colorado Boulder
Boulder, CO 80309-0430 USA
May 5, 2012 (14:13)