Mitochondrial heteroplasmy in vertebrates using ChIP-sequencing data.
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Authors
Rensch, Thomas
Villar, Diego
Horvath, Julie
Odom, Duncan T
Flicek, Paul
Publication Date
2016-06-27Journal Title
Genome Biol
ISSN
1474-7596
Publisher
Springer Science and Business Media LLC
Volume
17
Issue
1
Pages
139
Language
eng
Type
Article
Physical Medium
Electronic
Metadata
Show full item recordCitation
Rensch, T., Villar, D., Horvath, J., Odom, D. T., & Flicek, P. (2016). Mitochondrial heteroplasmy in vertebrates using ChIP-sequencing data.. Genome Biol, 17 (1), 139. https://doi.org/10.1186/s13059-016-0996-y
Abstract
BACKGROUND: Mitochondrial heteroplasmy, the presence of more than one mitochondrial DNA (mtDNA) variant in a cell or individual, is not as uncommon as previously thought. It is mostly due to the high mutation rate of the mtDNA and limited repair mechanisms present in the mitochondrion. Motivated by mitochondrial diseases, much focus has been placed into studying this phenomenon in human samples and in medical contexts. To place these results in an evolutionary context and to explore general principles of heteroplasmy, we describe an integrated cross-species evaluation of heteroplasmy in mammals that exploits previously reported NGS data. Focusing on ChIP-seq experiments, we developed a novel approach to detect heteroplasmy from the concomitant mitochondrial DNA fraction sequenced in these experiments. RESULTS: We first demonstrate that the sequencing coverage of mtDNA in ChIP-seq experiments is sufficient for heteroplasmy detection. We then describe a novel detection method for accurate detection of heteroplasmies, which also accounts for the error rate of NGS technology. Applying this method to 79 individuals from 16 species resulted in 107 heteroplasmic positions present in a total of 45 individuals. Further analysis revealed that the majority of detected heteroplasmies occur in intergenic regions. CONCLUSION: In addition to documenting the prevalence of mtDNA in ChIP-seq data, the results of our mitochondrial heteroplasmy detection method suggest that mitochondrial heteroplasmies identified across vertebrates share similar characteristics as found for human heteroplasmies. Although largely consistent with previous studies in individual vertebrates, our integrated cross-species analysis provides valuable insights into the evolutionary dynamics of mitochondrial heteroplasmy.
Keywords
Mitochondria, Animals, Vertebrates, Humans, Mitochondrial Diseases, DNA, Mitochondrial, Chromatin Immunoprecipitation, Sequence Analysis, DNA, Evolution, Molecular, High-Throughput Nucleotide Sequencing
Identifiers
External DOI: https://doi.org/10.1186/s13059-016-0996-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283036
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