RNA-DNA differences in human mitochondria restore ancestral form of 16S ribosomal RNA

Dan Bar-Yaacov, Gal Avital, Liron Levin, Allison L. Richards, Naomi Hachen, Boris Rebolledo Jaramillo, Anton Nekrutenko, Raz Zarivach, Dan Mishmar

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 (>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. By using traditional Sanger sequencing, we identified the A-to-U RDD in six different cell lines and representative primates (Gorilla gorilla, Pongo pigmaeus, and Macaca 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.

Original languageEnglish (US)
Pages (from-to)1789-1796
Number of pages8
JournalGenome research
Volume23
Issue number11
DOIs
StatePublished - Nov 1 2013

Fingerprint

16S Ribosomal RNA
Mitochondria
RNA
DNA
Mitochondrial DNA
Primates
Large Ribosome Subunits
Pongo
Gorilla gorilla
High-Throughput Nucleotide Sequencing
Thymine
Human Genome
Macaca mulatta
Vertebrates
Alleles

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Bar-Yaacov, D., Avital, G., Levin, L., Richards, A. L., Hachen, N., Rebolledo Jaramillo, B., ... Mishmar, D. (2013). RNA-DNA differences in human mitochondria restore ancestral form of 16S ribosomal RNA. Genome research, 23(11), 1789-1796. https://doi.org/10.1101/gr.161265.113
Bar-Yaacov, Dan ; Avital, Gal ; Levin, Liron ; Richards, Allison L. ; Hachen, Naomi ; Rebolledo Jaramillo, Boris ; Nekrutenko, Anton ; Zarivach, Raz ; Mishmar, Dan. / RNA-DNA differences in human mitochondria restore ancestral form of 16S ribosomal RNA. In: Genome research. 2013 ; Vol. 23, No. 11. pp. 1789-1796.
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Bar-Yaacov, D, Avital, G, Levin, L, Richards, AL, Hachen, N, Rebolledo Jaramillo, B, Nekrutenko, A, Zarivach, R & Mishmar, D 2013, 'RNA-DNA differences in human mitochondria restore ancestral form of 16S ribosomal RNA', Genome research, vol. 23, no. 11, pp. 1789-1796. https://doi.org/10.1101/gr.161265.113

RNA-DNA differences in human mitochondria restore ancestral form of 16S ribosomal RNA. / Bar-Yaacov, Dan; Avital, Gal; Levin, Liron; Richards, Allison L.; Hachen, Naomi; Rebolledo Jaramillo, Boris; Nekrutenko, Anton; Zarivach, Raz; Mishmar, Dan.

In: Genome research, Vol. 23, No. 11, 01.11.2013, p. 1789-1796.

Research output: Contribution to journalArticle

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AU - Bar-Yaacov, Dan

AU - Avital, Gal

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N2 - 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 (>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. By using traditional Sanger sequencing, we identified the A-to-U RDD in six different cell lines and representative primates (Gorilla gorilla, Pongo pigmaeus, and Macaca 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.

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Bar-Yaacov D, Avital G, Levin L, Richards AL, Hachen N, Rebolledo Jaramillo B et al. RNA-DNA differences in human mitochondria restore ancestral form of 16S ribosomal RNA. Genome research. 2013 Nov 1;23(11):1789-1796. https://doi.org/10.1101/gr.161265.113