Mitochondrial-nuclear co-evolution leads to hybrid incompatibility through pentatricopeptide repeat proteins
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Updated: Mar 10, 2026

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
Han-Ying Jhuang1,2, Hsin-Yi Lee1,3, Jun-Yi Leu4,2
1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Abstract:
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.
Insights
Mitochondrial-nuclear incompatibility, a cause of reproductive isolation, is driven by fast co-evolution between PPR proteins and mitochondrial RNA. This study identifies Ccm1 and 15S rRNA as key players in yeast hybrid incompatibility.
Area of Science:
- Evolutionary Biology
- Genetics
- Molecular Biology
Background:
- Mitochondrial-nuclear incompatibility significantly contributes to reproductive isolation between species.
- The precise mechanisms and evolutionary drivers of this incompatibility are not fully understood.
Purpose of the Study:
- To investigate the molecular basis of hybrid incompatibility between Saccharomyces cerevisiae and Saccharomyces bayanus.
- To identify specific proteins and RNA molecules involved in this interspecies reproductive barrier.
Main Methods:
- Identified a pentatricopeptide repeat-containing (PPR) protein, Ccm1, and its interaction with 15S rRNA.
- Assessed binding affinity between S. bayanus-Ccm1 and S. cerevisiae-15S rRNA.
- Analyzed the impact of mutations on PPR protein function and compatibility within Saccharomyces sensu stricto yeasts.
Main Results:
- S. bayanus-Ccm1 exhibits reduced binding affinity to S. cerevisiae-15S rRNA, causing respiratory defects in hybrid yeast.
- Single mutations in PPR motifs can rescue this incompatibility, highlighting the adaptability of PPR proteins.
- Approximately two-thirds of examined PPR proteins in related Saccharomyces species showed detectable incompatibility.
Conclusions:
- Fast co-evolution between flexible PPR proteins and mitochondrial RNA substrates is a likely common driver of mitochondrial-nuclear hybrid incompatibility.
- PPR proteins and their RNA targets are crucial in the speciation process through reproductive isolation.
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