The dynamics of clonal evolution: Dr. Jamie Blundell, Stanford University

Seminar | March 8 | 3:30-4:30 p.m. | 125 Li Ka Shing Center

 Center for Computational Biology

The dynamics of clonal evolution remain poorly understood despite having implications for the treatment of cancer and microbial infections. My work combines high-resolution lineage tracking using DNA barcodes, directed whole-genome-sequencing of adaptive clones, and mathematical models of mutational dynamics to understand clonal evolution at a quantitative level. Using this approach we are able to precisely measure key features of the evolutionary dynamics including the distribution of fitness effects for beneficial mutations. By characterizing the evolutionary dynamics across two environments we find that, despite differences in mutational mechanisms and fitness effects, early adaptive genetic diversity increases predictably, driven by expansion of many single-mutant lineages. However, a stochastic crash in diversity follows, caused by highly-fit double-mutants fed from exponentially growing single-mutants, a process related to the classic Luria-Delbruck experiment. I will highlight that, while some features of clonal evolution depend on details such as the population size, the distribution of fitness effects, and patterns of epistasis. However, others features, such as the presence of a diversity crash, are expected to be general. I will go onto discuss future work to use lineage tracking, longitudinal sequencing studies and mathematical modeling to characterize the clonal evolution taking place inside healthy and transformed tissues.