Organelle bottlenecks facilitate evolvability by traversing heteroplasmic fitness valleys

Bioenergetic organelles – mitochondria and plastids – retain their own genomes, and these organelle DNA (oDNA) molecules are vital for eukaryotic life. Like all genomes, oDNA must be able to evolve to suit new environmental challenges. However, mixed oDNA populations can challenge cellular bioenergetics, providing a penalty to the appearance and adaptation of new mutations. Here we show that organelle ‘bottlenecks’, mechanisms increasing cell-to-cell oDNA variability during development, can overcome this mixture penalty and facilitate the adaptation of beneficial mutations. We show that oDNA heteroplasmy and bottlenecks naturally emerge in evolutionary simulations subjected to fluctuating environments, demonstrating that this evolvability is itself evolvable. Usually thought of as a mechanism to clear damaging mutations, organelle bottlenecks therefore also resolve the tension between intracellular selection for pure oDNA populations and the ‘bet-hedging’ need for evolvability and adaptation to new environments. This general theory suggests a reason for the maintenance of organelle heteroplasmy in cells, and may explain some of the observed diversity in organelle maintenance and inheritance across taxa.