Mitochondrial-nuclear co-evolution leads to hybrid incompatibility through pentatricopeptide repeat proteins.

Mitochondrial-nuclear incompatibility has a major role in reproductive isolation between species. However, the underlying mechanism and driving force of mitochondrial-nuclear incompatibility remain elusive. Here, we report a pentatricopeptide repeat-containing (PPR) protein, Ccm1, and its interacting partner, 15S rRNA, to be involved in hybrid incompatibility between two yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus S. bayanus-Ccm1 has reduced binding affinity for S. cerevisiae-15S rRNA, leading to respiratory defects in hybrid cells. This incompatibility can be rescued by single mutations on several individual PPR motifs, demonstrating the highly evolvable nature of PPR proteins. When we examined other PPR proteins in the closely related Saccharomyces sensu stricto yeasts, about two-thirds of them showed detectable incompatibility. Our results suggest that fast co-evolution between flexible PPR proteins and their mitochondrial RNA substrates may be a common driving force in the development of mitochondrial-nuclear hybrid incompatibility.