RNA-DNA differences in human mitochondria restore ancestral form of 16S ribosomal RNA
- Dan Bar-Yaacov1,
- Gal Avital1,
- Liron Levin1,
- Allison Richards2,
- Naomi Hachen2,
- Boris Rebolledo Jaramillo3,
- Anton Nekrutenko3,
- Raz Zarivach1 and
- Dan Mishmar1,4
- ↵* Corresponding author; email: dmishmar{at}bgu.ac.il
Abstract
RNA transcripts are generally identical to the underlying DNA sequences. Nevertheless, RNA-DNA differences (RDDs) were found in the nuclear human genome and in plants and animals but not in human mitochondria. Here by deep sequencing of human mitochondrial DNA (mtDNA) and RNA, we identified three RDD sites at mtDNA positions 295 (C-to-U), 13710 (A-to-U, A-to-G) and 2617 (A-to-U, A-to-G). Position 2617, within the 16S rRNA, harbored the most prevalent RDDs (more than 30% A-to-U and ~15% A-to-G of the reads in all tested samples). The 2617 RDDs appeared already at the precursor polycistrone mitochondrial transcript. Using traditional Sanger sequencing we identified the A-to-U RDD in 6 different cell lines and representative primates (Gorilla gorilla, Pongo pigmaeus and Macca mulatta), suggesting conservation of the mechanism generating such RDD. Phylogenetic analysis of more than 1700 vertebrate mtDNA sequences supported a thymine as the primate ancestral allele at position 2617, suggesting that the 2617 RDD recapitulates the ancestral 16S rRNA. Modeling U or G (the RDDs) at position 2617 stabilized the large ribosomal subunit structure in contrast to destabilization by an A (the pre-RDDs). Hence, these mitochondrial RDDs are likely functional.
- Received May 30, 2013.
- Accepted July 30, 2013.
- © 2013, Published by Cold Spring Harbor Laboratory Press
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