Assessing the fitness consequences of mitonuclear interactions in natural populations

Abstract

Metazoans exist only with a continuous and rich supply of chemical energy from oxidative phosphorylation in mitochondria. The oxidative phosphorylation machinery that mediates energy conservation is encoded by both mitochondrial and nuclear genes, and hence the products of these two genomes must interact closely to achieve coordinated function of core respiratory processes. It follows that selection for efficient respiration will lead to selection for compatible combinations of mitochondrial and nuclear genotypes, and this should facilitate coadaptation between mitochondrial and nuclear genomes (mitonuclear coadaptation). Herein, we outline the modes by which mitochondrial and nuclear genomes may coevolve within natural populations, and we discuss the implications of mitonuclear coadaptation for diverse fields of study in the biological sciences. We identify five themes in the study of mitonuclear interactions that provide a roadmap for both ecological and biomedical studies seeking to measure the contribution of intergenomic coadaptation to the evolution of natural populations. We also explore the wider implications of the fitness consequences of mitonuclear interactions, focusing on central debates within the fields of ecology and biomedicine.

Keywords: coadaptation; coevolution; epistatic interactions; fitness; gene flow; mitochondria; mitochondrial medicine; speciation.

Fig. 1

Predicted organismal fitness, organelle function, and potential for maladapted mitonuclear genotypes during mitochondrial replacement theory. Three possible mitochondrial donors are shown, yielding variable degrees of conceivable mitonuclear incompatibilities. Importantly, deleterious mtDNA mutations (shown in red) have known fitness consequences, while those resulting from mitonuclear incompatibilities are predicted and likely complex.

Fig. 2

Examples of mitonuclear interactions: A) Multisubunit protein complexes of the electron transport chain, B) mitochondrial rRNA and nuclear ribosomal proteins of the mitochondrial ribosome, C) mitochondrial tRNA-Thr and nuclear threonyl-tRNA synthetase, and D) mitochondrial DNA and nuclear DNA polymerase gamma. Non-interacting mitochondrial-encoded components are presented in green, nuclear-encoded components are in yellow, and interacting residues that physically contact residues encoded by the other genome are in red. All models are from mammals, except C) which is from yeast. Interacting residues were identified following Sharbrough et al. 2017. PDB accessions used in structural depictions: 5LNK, 1ZOY, 1BGY, 1V54, 5ARA, 3J9M, 4YYE, and 5C51.

Fig. 3

Predicted organismal fitness and organelle function across generations. Note that in the F1 generation, mitonuclear incompatibilities will generally be masked by retention of a maternal allele. Most mitonuclear incompatibilities are predicted to occur in F2 or later generations. After Burton et al. 2013.