Fig. 1

Mitochondrial genomic landscape in MDS. A Human mtDNA map showing genes and intergenic regions in the circular plot. Colors of the circular bars represent mtDNA regions. mtDNA encodes 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and 13 proteins for the mitochondrial OXPHOS apparatus. These 13 components include seven (ND1, 2, 3, 4, 4L, 5, 6) of complex I, one (CYB) of the 11 subunits of complex III, three (CO1, 2, 3) of the 13 subunits of complex IV, and two (ATP6, 8) of the 16 subunits of complex V. Dots inside the circular plot represent substitutions of mtDNA identified in 494 MDS patients. Classes of substitutions are presented color-coded. Vertical axes represent the heteroplasmic fraction of each variant. B Number of mtDNA variants at different mtDNA genes. Colors represent the biotype of the variant. C Frequency and distribution of variants within the mitochondrial genome. Variant frequency normalized by dividing the number of variants per locus of each patient by length of the locus (kbp). D Associations between mtDNA variants and MDS clinical factors. The top panel displays the number of mtDNA variants per patient sorted first by the IPSS-R score, then by the number of mtDNA variants. A heatmap showing the location of each variant on the mitochondrial genome (middle), where the color of each bar represents the number of mtDNA variants in each gene. The mitochondrial genes are represented on the left. The bottom panel shows the clinical covariates for all 494 patients: Age, IPSS-R score, KPS, MDS types and present of cytogenetic abnormities and TP53 mutational status