RT Journal
A1 Bar-Yaacov, Dan
A1 Avital, Gal
A1 Levin, Liron
A1 Richards, Allison
A1 Hachen, Naomi
A1 Rebolledo Jaramillo, Boris
A1 Nekrutenko, Anton
A1 Zarivach, Raz
A1 Mishmar, Dan
T1 RNA-DNA differences in human mitochondria restore ancestral form of 16S ribosomal RNA
JF Genome Research 
JO Genome Research 
YR 2013 
FD August 02 
DO 10.1101/gr.161265.113 
SP gr.161265.113 
UL http://genome.cshlp.org/content/early/2013/08/02/gr.161265.113.abstract 
AB 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.