The functional importance of mitochondrial sequences with dual functions: overlapping protein–protein and protein–RNA gene sequences as test cases

Abstract Human mitochondrial DNA (mtDNA) contains 13 protein-coding subunits of the oxidative phosphorylation pathway, 22 tRNA and two rRNA genes. However, accumulating evidence suggests that mtDNA encodes additional overlapping genetic elements, including mitochondrial-derived peptides (MDPs) and alternative reading frames. Here, we assessed signatures of selection across 66 328 human mtDNAs and studied the potential impact of disease-causing mutation within these mtDNA overlapping sequences. B