Convergent pathways of reductive mitochondrial evolution characterised with hypercubic inference

For a striking example of mitochondrial behaviour beyond ATP generation, consider mitochondrion-related organelles (MROs). Hydrogenosomes, mitosomes, and other reduced mitochondrial forms have evolved through the loss of physical and functional features, from individual electron transport chain (ETC) complexes to oxidative phosphorylaytion and the very ability to produce ATP (and further). Reduction of mitochondria is a dramatic example of convergent evolution, occuring in every eukaryotic kingdom and many parallel times. Here, we use hypercubic inference, a class of methods from evolutionary accumulation modelling (EvAM), to explore the pathways of convergent mitochondrial reduction across eukaryotes. We find that most MRO diversity can be explained by small variations on two distinct pathways, starting with either the loss of Complex I or the loss of Complexes III/IV or TCA cycle steps, which tend to proceed over different characteristic timescales. We show that different clades, including ciliates and apicomplexans, reflect particular instances of these pathways. Using metabolic modelling, we connect the structure of these evolutionary pathways to the metabolic impact of the changes involved, suggesting a plausible explanation for the dramatically convergent nature of reductive evolution. We discuss this approach in connection with related theory on the genetic and functional reduction of mitochondria across organisms.