DNAseq sequencing of 5 unrelated individuals to study RNA-DNA Differences in Human Mitochondria Restore Ancestral Form of 16S Ribosomal RNA

RNA sequences are generally identical to the underlying DNA sequences but there are known exceptions. These RNA-DNA differences (RDDs) have been found in the nuclear genomes of human cells and in the mitochondria of plants and animals but not in human mitochondria. Here by deep sequencing of DNA and RNA of human mitochondria, we identified 3 RDD sites including an A-to-U and an A-to-G RDD at position 2617. Examination of the precursor polycistronic mitochondrial transcripts shows that the RDD formation occurs post-transcriptionally. Phylogenetic analysis shows that the ancestral allele at position 2617 was a thymine or a guanine. Thus the RDD formation recapitulates the ancestral form of 16S rRNA. Our findings show that RDD formation like other RNA processing steps is conserved across species and likely has functional significance.