Mito-nuclear Incompatibilities and Mitochondrial Replacement Therapy

Mitochondrial replacement therapy (MRT) is a human reproductive technology by which the mitochondria of a recipient’s eggs are effectively replaced by those of a donor, potentially eliminating harmful mitochondrial mutations carried by the recipient. However, concerns have been raised that MRT may lead to problems due to incompatibilities between the nuclear genome of the recipient and mitochondrial genome of the donor. Whether this is likely to be a problem is investigated using 226 estimates, taken from the literature, of the effect of replacing the “native” by a “foreign” mitochondrial DNA (mtDNA) from the same species in a variety of animals. In approximately half of the cases (45%), strains with the foreign mtDNA have higher fitness than those with the native mtDNA, and on average the native strains are only 3% fitter. Based on these results it is argued that incompatibilities between the mitochondrial and nuclear genomes are not likely to be a problem for MRT. Main text It has been suggested that incompatibilities between the mitochondrial and nuclear genomes could be a risk factor in mitochondrial replacement therapy (MRT) (REINHARDT et al. 2013; GEMMELL AND WOLFF 2015; HAMILTON 2015; MORROW et al. 2015). Incompatibilities between the mitochondrial and nuclear genomes can arise because the vast majority of genes that contribute products to the mitochondrion are located in the nuclear genome (CALVO et al. . CC-BY-NC-ND 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/078329 doi: bioRxiv preprint first posted online Sep. 30, 2016;