Ancient Out-of-Africa Mitochondrial DNA Variants Associate with Distinct Mitochondrial Gene Expression Patterns

PLoS Genet. 2016 Nov 3;12(11):e1006407. doi: 10.1371/journal.pgen.1006407. eCollection 2016 Nov.


Mitochondrial DNA (mtDNA) variants have been traditionally used as markers to trace ancient population migrations. Although experiments relying on model organisms and cytoplasmic hybrids, as well as disease association studies, have served to underline the functionality of certain mtDNA SNPs, only little is known of the regulatory impact of ancient mtDNA variants, especially in terms of gene expression. By analyzing RNA-seq data of 454 lymphoblast cell lines from the 1000 Genomes Project, we found that mtDNA variants defining the most common African genetic background, the L haplogroup, exhibit a distinct overall mtDNA gene expression pattern, which was independent of mtDNA copy numbers. Secondly, intra-population analysis revealed subtle, yet significant, expression differences in four tRNA genes. Strikingly, the more prominent African mtDNA gene expression pattern best correlated with the expression of nuclear DNA-encoded RNA-binding proteins, and with SNPs within the mitochondrial RNA-binding proteins PTCD1 and MRPS7. Our results thus support the concept of an ancient regulatory transition of mtDNA-encoded genes as humans left Africa to populate the rest of the world.

MeSH terms

  • African Continental Ancestry Group
  • Base Sequence / genetics
  • DNA Copy Number Variations / genetics
  • DNA, Mitochondrial / biosynthesis*
  • DNA, Mitochondrial / genetics
  • Evolution, Molecular*
  • Gene Expression Profiling
  • Haplotypes
  • Human Genome Project
  • Humans
  • Mitochondria / genetics*
  • Mitochondrial Proteins / biosynthesis*
  • Mitochondrial Proteins / genetics
  • Polymorphism, Single Nucleotide
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics
  • Ribosomal Proteins / biosynthesis
  • Ribosomal Proteins / genetics


  • DNA, Mitochondrial
  • MRPS7 protein, human
  • Mitochondrial Proteins
  • PTCD1 protein, human
  • RNA-Binding Proteins
  • Ribosomal Proteins

Grant support

This study was funded by research grants from the Israeli Science Foundation (ISF 610/12), from the Binational Science Foundation (BSF) 2013060, and from the US Army Life Science division grant 67993LS awarded to DM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.