Mitochondria single nucleotide variation across six blood cell types

Abstract

It has been shown that heteroplasmic mitochondrial DNA variants can be tissue specific. However, whether mitochondrial DNA variants are specific by blood cell types has not been investigated. Motivated by this question and using mitochondria sequences extracted from RNAseq data from six distinct blood cell types (neutrophil, monocyte, myeloid dendritic, natural killer, T and B), we thoroughly compared SNPs and heteroplasmies among these cell types. Each cell type from each subject was sequenced at four time points used as biological replicates. We found that mitochondria content is low in neutrophil compared to the other five blood cell types. Subsequent analysis on the other five blood cell types showed that at the SNP level, there was no discrepancy. At the heteroplasmy level, we observed good concordances among all blood cell types. However, the allele frequencies of the heteroplasmy differed between blood cell types for certain heteroplasmic sites. Furthermore, we identified five tri-allelic sites (1610, 2617, 8303, 12146, 13710) that are likely caused by RNA editing. Three out of these five sites are located at the ninth position of tRNA genes, and are likely resulting from post-transcriptional methylation.