Investigating mitonuclear interactions in human admixed populations

https://www.nature.com/articles/s41559-018-0766-1

Arslan A. Zaidi & Kateryna D. Makova

• The authors explore signatures of mitonuclear incompatibility and coevolution in six admixed human populations from the Americas
• They hypothesize that incompatibility might arise between e.g. mtDNA origins of replication and nuclear-encoded mtDNA replication machinery and therefore, might lead to a decrease in mtDNA replication efficiency. The authors therefore predict that if mito/nuclear discordance is increased in admixed individuals, mtDNA copy number may consequently decrease.
• Given two admixed human populations with different mitochondrial haplotypes, if all females are from population 1, and all males from population 2, inherited autosomal loci will be a mixture of the two populations whereas the mtDNA will be purely from population 1. This may place selection in favour of nuclear-encoded mitochondrial genes from population 1, and such progeny may suffer mito-nuclear mismatch (see Fig 1b). 
• The authors found statistically significant negative correlation between mtDNA copy number and mitonuclear DNA discordance in admixed individuals, although the relationship was rather noisy (Fig 3a, R^2=0.04).
• They find significant enrichment of ancestry at nuclear-encoded mitochondrial genes towards the source populations contributing the most prevalent mtDNA haplogroups, indicating compensatory selective effects.