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Tug-of-war between driver and passenger mutations in cancer and other adaptive processes.


ABSTRACT: Cancer progression is an example of a rapid adaptive process where evolving new traits is essential for survival and requires a high mutation rate. Precancerous cells acquire a few key mutations that drive rapid population growth and carcinogenesis. Cancer genomics demonstrates that these few driver mutations occur alongside thousands of random passenger mutations--a natural consequence of cancer's elevated mutation rate. Some passengers are deleterious to cancer cells, yet have been largely ignored in cancer research. In population genetics, however, the accumulation of mildly deleterious mutations has been shown to cause population meltdown. Here we develop a stochastic population model where beneficial drivers engage in a tug-of-war with frequent mildly deleterious passengers. These pas

SUBMITTER: McFarland CD 

PROVIDER: S-EPMC4210325 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature