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Precise Annotation Of Human, Chimpanzee, Rhesus Macaque And Mouse Mitochondrial Genomes Using 5’ And 3’ End Small RNAs

Zhi Cheng, Haishuo Ji, Xiufeng Jin, Bo Wang, Tungon Yau, Ze Chen, Defu Chen, Wenjun Bu, Daqing Sun, Shan Gao

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AbstractUsing 5’ and 3’ end small RNAs, we annotated human, chimpanzee, rhesus macaque and mouse mitochondrial genomes at 1 base-pair (bp) resolution to cover both strands of the mammalian mitochondrial genome entirely without leaving any gaps or overlaps. The precise annotation of all coding and non-coding genes (e.g. ncMT1, MDL2 and MDL1AS) led to the discovery of novel functions and mechanisms of mitochondrion. In this study, we defined the conserved sequence block (CSB) region to span five CSBs (CSB1, CSB2, CSB3, LSP and HSP) and identified the motifs of five CSBs in the mitochondrial displacement loop (D-loop) regions of 52 mammals. The conserved arrangement of these five CSBs in 17 primates inspired us to investigate the function of the mtDNA D-loop, which has been puzzling scientists for more than 50 years. We found that 5’ sRNAs of MDL1AS control the expression levels of mitochondrial genes as a whole by a negative feedback mechanism. Thus, the precise annotations of three CSBs (CSB2, LSP and HSP) in more species will help to understand the function of the mtDNA D-loop. The precision annotation of animal mitochondrial genomes also provides abundant information for studying the molecular phylogenetics and evolution of animals.