Mitochondrial heteroplasmy in vertebrates using ChIP-sequencing data

Abstract

BackgroundMitochondrial 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.ResultsWe 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.ConclusionIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-0996-y) contains supplementary material, which is available to authorized users.

The global diversity of the major parasitic nematodeHaemonchus contortusis shaped by human intervention and climate

“…Realignment around indels was applied with GATK 70 and SNP were subsequently called using samtools 71 mpileup using only reads that achieved a mapping quality of 30 and base quality of 30. The occurrence of heterozygous sites in mtDNA, known as heteroplasmy, has been described across vertebrate species 72 and in other nematode species, including C. briggsae 73 and C. elegans 74 . However, heterozygous sites may also occur as technical artefacts as a result of genetically similar sequences shared between the nuclear and mitochondrial genomes, i.e ., numts 75 .…”

Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing

“…Protein coding genes encode essential subunits of the electron transport chain (ETC) complexes, while the tRNA and rRNA genes encode components of the mitochondrial translation machinery. The mitogenome is maternally inherited, is non-recombining and has a higher mutation rate than the nuclear genome 1 , 2 . These properties have made it an attractive study locus for phylogenetics, population genetics and forensics.…”

“…Recently, Rensch et al . 1 used publicly available ChIP-Seq data from 16 species to evaluate patterns of heteroplasmy across the vertebrate phylogeny and concluded that divergent species show similar patterns in frequency and location of heteroplasmy. This study discovered relatively few heteroplasmies, likely due to the high frequency cut off used, and few individuals available for some species.…”

Population level mitogenomics of the long-lived Greater Mouse-eared bat,Myotis myotis, reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing

“…Protein coding genes encode essential subunits of the electron transport 50 chain (ETC) complexes, while the tRNA and rRNA genes encode components of the 51 mitochondrial translation machinery. The mitogenome is maternally inherited, is non- 52 recombining and has a higher mutation rate than the nuclear genome [1,2]. These 53 properties have made it an attractive study locus for phylogenetics, population genetics and 54 forensics.…”