Lessons from Evolution for the Fight Against Cancer

Shuffling the Deck: Pevzner and Tesler analysis of genetic rearrangements in human-mouse evolution from a common mammalian ancestor, work that could aid in understanding gene rearrangements that occur in individuals with cancer.

Bioinformatics work by computer science professor Pavel Pevzner and mathematics professor Glenn Tesler is yielding major insights into human evolution - and cancer. Pevzner studies evolutionary genomic rearrangements that play out over millions of years, and chromosomal rearrangements implicated in certain types of cancer. In June, Pevzner and Tesler predicted the existence of evolutionary faults - hotspots where gene rearrangements are more likely to occur and change the architecture of the genome. Such faults may be limited to approximately 400 'fragile' regions that account for only 5% of the human genome. That paper, in Proceedings of the National Academy of Sciences, departed from the widely-held 'random breakage' theory of evolution, but quickly gained acceptance. Indeed, in September, a team lead by Jim Kent and David Haussler at UC Santa Cruz (who are largely credited with assembling the human genome) were able to pinpoint some of these genomic fault zones. Using similar computational tools, Pevzner and his postdoc Ben Raphael are working with biologists at the UCSF Cancer Center to analyze chromosomal rearrangements in tumors. Their September publication in Bioinformatics includes an analysis that yields a complete picture of the genomic architecture of a complex tumor genome. As soon as the reconstructions of other tumor genomes are completed, Pevzner will investigate whether breakpoints implicated in cancers correlate with the breakpoints evident in human-mouse evolution from a common ancestor 75 million years ago.