Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans

Nat Commun. 2020 Apr 8;11(1):1740. doi: 10.1038/s41467-020-15336-3.

Abstract

Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5-25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / genetics*
  • DNA, Mitochondrial / genetics*
  • Family
  • Female
  • Haplotypes / genetics
  • Humans
  • Male
  • Models, Genetic
  • Paternal Inheritance / genetics*
  • Pedigree
  • Reproducibility of Results

Substances

  • DNA, Mitochondrial