Speaker: Dr. Gill Bejerano

Affiliation: University of California, Santa Cruz

Title: Ultra-Conservation in the Human Genome

The sequence of functional DNA is often observed to be under selective

pressure to maintain its function. Indeed, sequence conservation

between diverged species is a hallmark of functional importance.

However, nearly all types of functional sequences acquire some changes

between diverged species, without harming their function. For example,

homologous genes in the human and mouse genomes, thought to have

diverged over 80 million years ago, are only 85% identical in

sequence, on average.

And yet, in a systematic evaluation of the complete human, mouse and

rat genomes, we find hundreds of syntenic regions that are perfectly

conserved between all three. These unexpected, so called

ultra-conserved regions, challenge our current understanding of the

human genome. Moreover, the majority of these regions do not overlap

protein-coding exons.

Initial analysis has shown these regions to be preferentially located

overlapping exons of genes involved in RNA processing, or in introns

or nearby genes involved in the regulation of transcription and

development. And while nearly all of these regions are found in

chicken, and most are also found in frog and jawed fish, virtually

none could be traced using direct sequence similarity beyond the

vertebrates.

Deciphering the functions, evolutionary origins and molecular

mechanisms that maintain these regions pose exciting computational

and experimental challenges. I will present the work which has led to

this discovery, and that of a broader collection of human putative

functional elements, and discuss our current computational and

experimental efforts to better understand this phenomenon.

Joint work with David Haussler, Mathieu Blanchette and Sofie Salama.

see http://www.soe.ucsc.edu/~jill/ for additional information.