Admixture Effects on Coevolved Metabolic Systems.

Roxanne R Zascavage,John V Planz

doi:10.3389/fgene.2018.00634

Abstract

Oxidative phosphorylation (OXPHOS) is the primary energy generating system in eukaryotic organisms. The complexes within the OXPHOS pathway are of mixed genomic origin. Although most subunit-coding genes are located within the nuclear genome, several genes are coded for in the mitochondrial genome. There is strong evidence to support coadaptation between the two genomes in these OXPHOS gene regions in order to create tight protein interactions necessary for a functional energetics system. In this study, we begin to assess the physiological impact of separating coevolved protein motifs that make up the highly conserved energy production pathway, as we hypothesize that divergent matings will significantly diminish the protein interactions and therefore hinder efficient OXPHOS activity We measured mitochondrial activity in high energy-demanding tissues from six strains of Mus musculus with varying degrees of mixed ancestral background. Mice with divergent mitochondrial and nuclear backgrounds consistently yielded lower mitochondrial activity. Bioinformatic analysis of common single nucleotide variants across the nuclear and mitochondrial genomes failed to identify any non-synonymous variants that could account for the energetic differences, suggesting that interpopulational mating between ancestrally distinct groups influences energy production efficiency.

Highlights

Based on the results presented here, as well as the literature discussed within surrounding such variances, we theorize that the decrease in oxidative phosphorylation (OXPHOS) efficiency is likely due to incompatibilities between the nuclear and mitochondrial protein isoforms or regulatory regions that have become disjunct as a result of admixture
The ANOVA results determined there was no statistical difference between the oxygen consumption rate (OCR) in the mildadmixture groups and the no-admixture groups in either the hepatic or the cardiac tissues (p > 0.05)
If this study had identified a single SNP or a combination of SNPs that accounted for the shift in energetic levels in the highly admixed mice, the discussion on cytonuclear incompatibility would be void because a mutation would explain these results

Summary

Introduction

In humans and other bilateral mammals, these complexes consist of ∼90 subunits, of which 13 are encoded in the mitochondrial genome and the remaining 77 from the nuclear genome. This bi-genomic formation makes the OXPHOS pathway unique in that it requires the interaction of proteins of differing origins to collectively function (Table 1). More than thirty years of scientific research has provided strong evidence for coadaptation of the two genomes in the gene regions coding for OXPHOS subunits (Goodman, 1982; Rand et al, 2004; Bar-Yaacov et al, 2012; Osada and Akashi, 2012; Sloan et al, 2018). Experimental approaches that combined nuclear and mitochondrial backgrounds from closely related species have demonstrated this decrease in energy

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