Clonal dynamics: experimental evolution, clonal hematopoiesis and cancer risk
The dynamics of genetic diversity in large clonally-evolving cell populations are poorly understood, despite having implications for the detection and treatment of cancers. I will describe work where we combine barcode lineage tracking, sequencing of adaptive clones, and mathematical modelling of mutational dynamics to understand how genetic diversity changes in an experimental system. We find that, despite differences in beneficial mutational mechanisms and fitness effects between environments, early adaptive genetic diversity increases predictably, driven by the expansion of many single-mutant lineages.
However, a crash in diversity follows, caused by highly-fit double-mutants fed from exponentially growing single-mutants, a process closely related to the classic Luria-Delbruck experiment. The diversity crash is likely to be a general feature of clonal evolution, however its timing and magnitude is stochastic. I will go onto describe more recent work applying some of these insights to quantitatively understand the clonal evolution that drives clonal hematopoiesis and their implications for predicting subsequent hematologic cancers.
Department of Oncology at CRUK Cambridge Center
Director of research