The Red Queen in mitochondria: cyto-nuclear co-evolution, hybrid breakdown and human disease.

Jui-Yu Chou,Jun-Yi Leu

doi:10.3389/fgene.2015.00187

Abstract

Cyto-nuclear incompatibility, a specific form of Dobzhansky-Muller incompatibility caused by incompatible alleles between mitochondrial and nuclear genomes, has been suggested to play a critical role during speciation. Several features of the mitochondrial genome (mtDNA), including high mutation rate, dynamic genomic structure, and uniparental inheritance, make mtDNA more likely to accumulate mutations in the population. Once mtDNA has changed, the nuclear genome needs to play catch-up due to the intimate interactions between these two genomes. In two populations, if cyto-nuclear co-evolution is driven in different directions, it may eventually lead to hybrid incompatibility. Although cyto-nuclear incompatibility has been observed in a wide range of organisms, it remains unclear what type of mutations drives the co-evolution. Currently, evidence supporting adaptive mutations in mtDNA remains limited. On the other hand, it has been known that some mutations allow mtDNA to propagate more efficiently but compromise the host fitness (described as selfish mtDNA). Arms races between such selfish mtDNA and host nuclear genomes can accelerate cyto-nuclear co-evolution and lead to a phenomenon called the Red Queen Effect. Here, we discuss how the Red Queen Effect may contribute to the frequent observation of cyto-nuclear incompatibility and be the underlying driving force of some human mitochondrial diseases.

Highlights

Mitochondria are the major energy source of the cell and are involved in many important cellular functions (McBride et al, 2006)
Cyto-nuclear incompatibility is a specific form of DobzhanskyMuller incompatibility, which is caused by improper interactions between genetic loci that have functionally diverged in two different species (Figure 2; Dobzhansky, 1937; Muller, 1942)
A possible explanation for why cyto-nuclear incompatibility is so common among currently identified incompatible genes could be the arms race and co-evolution between mitochondrial and nuclear genomes

Summary

Introduction

Mitochondria are the major energy source of the cell and are involved in many important cellular functions (McBride et al, 2006) Mitochondria harbor their own genome (mtDNA), mitochondrial genomes are severely degenerated and comprise a few to dozens of protein-coding genes, while the majority have been transferred to the host nuclear genome (Burger et al, 2003). Hundreds of nucleus-encoded proteins are required (Meisinger et al, 2008) This close relationship between mitochondria and the host cell guarantees tight co-evolution between their genomes, which implies that any mismatch may result in severe defects in cellular fitness. At least three types of driving forces have been speculated to cause cyto-nuclear incompatibility: (a) adaptive divergence, (b) compensatory coadaptation, and (c) intergenomic conflict. We will discuss the possibility that the internal evolutionary arms race between mitochondrial and nuclear genomes accelerates co-evolution and causes hybrid incompatibilities, as well as the implication of cytonuclear incompatibility in human disease

Adaptive Divergence in Mitochondrial DNA

Selfish Mitochondrial DNA

The Red Queen and Hybrid Breakdown

Red Queen in Mitochondria and Human Disease

Conclusion