Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans.
Level 3 - non-randomized controlled study
Large observational genomic cohort study evaluating pedigree transmission
PubMed 32269217 · doi:10.1038/s41467-020-15336-3
What was done
The authors screened nuclear whole-genome sequencing data from 11,035 family trios to identify instances of apparent biparental or paternal mitochondrial DNA (mtDNA) transmission (apparent heteroplasmic haplotypes). When detected, they analyzed nuclear whole-genome sequence structures to determine whether the observed mtDNA-like sequences were located in the mitochondrial genome or integrated into the nuclear genome as large nuclear-mitochondrial DNA segments (mega-NUMTs).
What was found
A signature resembling biparental mtDNA inheritance was initially detected in 7 of 11,035 trios (0.06% of offspring), with apparent heteroplasmic allelic fractions of 5% to 25%. Nuclear whole-genome analysis showed that all 7 families possessed large, rare or unique mega-NUMTs that were transmitted autosomally from the father. Mega-NUMTs were independently detected in 0.13% of fathers. The allelic fractions were accounted for by complex concatenated mtDNA-derived sequence rearrangements integrated into the nuclear genome, yielding no evidence of true paternal mtDNA transmission.
Why it matters
This study clarifies a major controversy in genetics by demonstrating that reports of paternal mitochondrial DNA inheritance are sequencing artifacts caused by rare, large nuclear insertions of mitochondrial DNA. It reaffirms the standard model of strict maternal mtDNA inheritance in humans.
Limits
The abstract lacks specific phenotypic or health-related data regarding the individuals carrying mega-NUMTs. It does not provide the precise base-pair sizes or chromosomal locations of the identified mega-NUMTs. Findings rely on genomic sequencing datasets without functional cellular localization assays described in the abstract.
Cited by
- supports All mitochondria in the human body are derived exclusively from the maternal egg.