| dc.description.abstract | Cooperation facilitates the evolution of complex biological systems by enabling fitness benefits like resource sharing and divisions of labor. Despite these benefits, cooperation is vulnerable to cheating, whereby an entity benefits from cooperative behaviors of others without reciprocating. Cooperation and cheating are widespread evolutionary strategies, occurring across a range of scales, from the molecular to societal. Eukaryotic cells arose from a cooperative endosymbiosis between a bacterium and a host cell. Mitochondrial genomes are descendants of the ancestral bacterial genome; they cooperate with each other and with the host by contributing to energy production. In return, the host supplies resources for replicating mitochondrial DNA (mtDNA). Like other examples of cooperative systems in biology, eukaryotic cells are vulnerable to cheating. Selfish mitochondrial genomes are mutant mtDNA (∆mtDNA) copies that proliferate without contributing to host fitness, constituting a common cause of disease. What mechanisms facilitate ∆mtDNA propagation, and what conditions determine whether the selfish or cooperative genome has the evolutionary upper hand? By developing experiments to quantitatively measure shifts in the relative prevalence of selfish and cooperative mtDNA, across varying conditions and host genotypes, I identified key ways in which ∆mtDNA propagates across generations by cheating within the germline. In particular, a ∆mtDNA variant in the species Caenorhabditis elegans proliferates by taking advantage of physiological mechanisms that are adapted to deal with stress. These include compensatory mtDNA replication, whereby the cell inadvertently makes more copies of the mutant genome in an attempt to maintain normal mitochondrial function. The mitochondrial unfolded protein response and the protein FoxO, both of which regulate important aspects of metabolic homeostasis, further facilitate selfish ∆mtDNA propagation. Remarkably, FoxO promotes propagation of ∆mtDNA while also functioning to mitigate its harmful effects on host fitness; however, each of these functions of FoxO is context-specific, depending on nutrient status. Thus, in addition to elucidating mechanisms by which ∆mtDNA cheats, I identified important ways in which the host genome interfaces with its environment to shape the competition dynamics between mitochondrial genomes. This work clarifies some highly consequential interactions within the cell in light of the evolutionary forces that continue to shape them. | |
