Usually each of these copies is identical as they originate from the 200 copies present in each primordial germ cell laid down just after gastrulation and are then clonally expanded. Interestingly though, the process that eliminates sperm mtDNA in intraspecific crosses does not mediate its loss in interspecific crosses. In SCNT embryos, the mtDNA accompanying the somatic cell is either eliminated during preimplantation development, resulting in homoplasmic transmission of recipient oocyte mtDNA, or persists resulting in heteroplasmy, a combination of donor cell and recipient oocyte mtDNA. Transmission of donor cell mtDNA ranges from 0 to 63% in preimplantation embryos and 0 to 59% in live offspring. This tends to be independent of whether intra- or inter-specific SCNT is performed. For Niraparib example, donor cell mtDNA has been detected in bovine embryos derived by both intra- and inter-specific NT, though not in all cases, and in caprine embryos and porcine offspring derived by interspecific SCNT. However, as there are sequence variations in the mtDNA coding genes for breeds within the same species, this can result in different combinations of amino acid synthesis and the degree of heteroplasmy could considerably reduce the ability of any resultant stem cells to generate sufficient ATP through OXPHOS. Following iSCNT, donor cell mtDNA has been detected at the 16- cell stage in human-bovine embryos, the blastocyst stage in macaque-rabbit embryos and in a small minority of MLN4924 caprineovine embryos. However, the tendency is for donor cell mtDNA in more genetically diverse fusions to be eliminated during development, perhaps reflecting the difference in size of the mitochondrial genome between species. In porcine cells, it is approximately 16.7 kb whilst the human and murine mtDNA genomes are 16.6 kb and 16.2 kb, respectively. Furthermore, the increased genetic distance between the donor cell and the recipient oocyte could also affect nucleomitochondrial compatibility. To this extent, interspecies cybrid studies, where somatic cell karyoplasts were fused to enucleated cytoplasts, demonstrated that increased genetic distance between the two fusion partners resulted in decreased ATP output most likely due to the nuclear-encoded polypeptides of the ETC failing to interact with the mtDNA-encoded subunits. Furthermore, nucleomitochondrial incompatibility could impact on mtDNA replication, which is mediated through nuclear-encoded factors. These include themtDNA-specific DNA polymerase, Polymerase Gamma, its catalytic and accessory subunits; mitochondrial transcription factor A which generates the primer for replication; and Twinkle, the mtDNA-specific helicase.