Cytonuclear integration and co-evolution

The partitioning of genetic material between the nucleus and cytoplasmic (mitochondrial and plastid) genomes within eukaryotic cells necessitates coordinated integration between these genomic compartments, with important evolutionary and biomedical implications. Classic questions persist about the pervasive reduction of cytoplasmic genomes via a combination of gene loss, transfer and functional replacement — and yet why they are almost always retained in some minimal form. One striking consequence of cytonuclear integration is the existence of ‘chimeric’ enzyme complexes composed of subunits encoded in two different genomes. Advances in structural biology and comparative genomics are yielding important insights into the evolution of such complexes, including correlated sequence changes and recruitment of novel subunits. Thus, chimeric cytonuclear complexes provide a powerful window into the mechanisms of molecular co-evolution. Eukaryotic cells must regulate not only their nuclear genomes but also the intimate functional interplay with organelle genomes, such as those in mitochondria and plastids. This Review discusses the functional and evolutionary implications of cellular genomes being partitioned between the nucleus and organelles, including the translocation of genes and gene products, chimeric enzyme complexes and insights into molecular co-evolution.