Chance and dance with cells’ power plants

Mitochondria and chloroplasts power complex life. They retain genomes from their endosymbiotic origins, encoding vital bioenergetic and metabolic machinery. These essential genomes form dynamic populations in eukaryotic cells, and are subject to damaging mutations. How do these organelles avoid Muller’s ratchet – the buildup of mutations until function is lost?

I’ll talk about our work combining stochastic modelling, physical simulation, bioinformatics, and network modelling with genetic and cell-biological experiments to explore the answers that different eukaryotes have evolved to this question. The case of humans and many animal mitochondria will be familiar to several folks at Imperial – a “germline bottleneck” exploits cellular stochasticity to segregate damage across offspring. But other taxa employ rather different mechanisms, leading to genetic tradeoffs which we argue can be addressed by controlling the physical behaviour of organelles. I’ll try and move towards a general picture coupling genetic and physical behaviours across different eukaryotic developmental plans, and discuss some translational applications of this picture.