Abstract:

Eukaryotic cells contain numerous copies of mitochondrial DNA (mtDNA), allowing for the
coexistence of mutant and wild-type mtDNA in individual cells. The fate of mutant mtDNA
depends on their relative replicative fitness within cells and the resulting cellular fitness within
populations of cells. Yet the dynamics of the generation of fragmented mutant mtDNA and the features that
inform their fitness remain unaddressed. Here we utilize long read single-molecule sequencing
to track mtDNA mutational trajectories in Saccharomyces cerevisiae. We show a previously
unseen pattern that constrains subsequent excision events in mtDNA fragmentation. Our high resolution

analysis confirms the generation of rare and contentious non-periodic mtDNA structures that
lead to persistent diversity within individual cells. Finally, we show that measurements of relative
fitness of mtDNA fit a phenomenological model that highlights important biophysical parameters
governing mtDNA fitness. I will end by providing an outlook where mtDNA dynamics provides

an experimental system to quantitatively study multilevel selection and its implications.

   Sidhartha Goyal received his PhD in Physics at Princeton in 2009 and then moved to KITP, UC Santa Barbara for a postdoc. He got his first degree in Electrical Engineering from IIT Bombay.  Since 2014, he has been an Assistant Professor in the Physics Department at University of Toronto’s downtown (St. George) campus.