RT Journal Article
SR Electronic
T1 The Dynamics of Adaptive Genetic Diversity During the Early Stages of Clonal Evolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 170589
DO 10.1101/170589
A1 Jamie R. Blundell
A1 Katja Schwartz
A1 Danielle Francois
A1 Daniel S. Fisher
A1 Gavin Sherlock
A1 Sasha F. Levy
YR 2017
UL http://biorxiv.org/content/early/2017/07/31/170589.abstract
AB The dynamics of genetic diversity in large clonally-evolving cell populations are poorly understood, despite having implications for the treatment of cancer and microbial infections. Here, we combine barcode lineage tracking, sequencing of adaptive clones, and mathematical modelling of mutational dynamics to understand diversity changes during experimental evolution. We find that, despite differences in beneficial mutational mechanisms and fitness effects between two 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 and depends on the population size, the distribution of beneficial fitness effects, and patterns of epistasis.