Mitochondrial to nuclear gene transfer via synthetic evolution

Jean-Paul di RAGO

Institut de Biochimie et Génétique Cellulaires, UMR CNRS 5095, F-33077, Bordeaux, F.


   Mitochondria, the centers of cellular energy production, have transferred the majority of their own genetic material to the nuclear genome during evolution. Yet a handful of genes remain in all mitochondrial genomes, despite their susceptibility to damaging by metabolic byproducts and mutations. The consequences of mtDNA mutations are significant: they are implicated in a range of severe diseases, and the mutations accumulated during a lifetime are believed to lead to neurodegenerative disorders and the ageing process itself. This raises the question of why the mitochondrial genome still exists, despite the potentially severe consequences on fitness in all eukaryotes, and what are the cellular processes that limit or support mitochondrial gene expression from the nucleus? These questions can be answered by synthetic ``allotopic'' expression of these genes from the protected environment of the nucleus. Yeast is uniquely suited to study this problem because it is one of few organisms where mtDNA can be manipulated, and is amenable to genomic and synthetic biology techniques. Using this approach, we found that successful transfer of mtDNA to the nucleus requires adaptations not only in the allotopic protein, but also in several cellular processes to protect it from degradation both outside and inside the organelle.