Age dependent accumulation of mitochondrial DNA (mtDNA) mutations is generally accepted as one of the factors involved in the mechanisms of aging. Therefore, allotopic expression of mitochondrial genes (the transfer of mitochondrial genes to nucleus) is proposed to rescue the cells from the deleterious effects of mtDNA mutations. In this study we analysed the possibility of the usage of Reclinomonas americana (R. americana) mtDNA as an evolutionary protected template for allotopic expression of human mtDNA encoded OXPHOS subunits. MtDNA of R. americana is one of the biggest mitochondrial genomes and represents very early stages of mtDNA evolution. R. americana mtDNA uses standard genetic code. In this study we compared 1) R. americana and human mtDNAs, 2) 25 subunits of OXPHOS complexes encoded by R. americana mtDNA and their both nuclear and 13 mitochondrial human orthologs. The DNA similarity was only found in one short region which is a part of COX3 gene. The protein similarity was more conserved than DNA. The similarity of human nuclear orthologs of R. americana mtDNA genes was higher than mitochondrial orthologs. Our results suggest that mtDNA has a higher mutation rate than nuclear DNA, and the evolutionary change of human mitochondrial genetic code usage had mutational consequences that created one of the barriers in the transfer of mitochondrial genome to nucleus. Therefore R. americana mtDNA can be used as a source or template for allotopic expression in humans. For example, it can provide important insights during the design of the new subunit DNAs to functionally replace the existing ones.