Cytonuclear integration and co-evolution

Abstract

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.

Figure 1.

Variation in mitochondrial gene content across eukaryotic lineages. Filled squares indicate the presence of the gene in the mitogenome of the corresponding species. Gene ordering reflects analysis of gene retention rates by Johnston and Williams (with the exception of the four left-most genes, which were not included in that analysis). Genes are colour-coded by functional category. Gene content is based on summary by Roger et al., incorporating additional sampling and reannotations by Janouškovec et al.. In all known eukaryotes, the large complement of proteincoding genes ancestrally found in the mitochondrial progenitor has been reduced to some subset of these 69 genes, reflecting massive gene loss early in the evolution of eukaryotes. The extent of the reduction in gene content varies considerably across eukaryotic lineages, but genes encoding certain key subunits of OXPHOS complexes are almost always retained in the mitogenome. Taxonomic abbreviations are as follows. Am, Amoebozoa; Crypt, Cryptophyta; Gla, Glaucophyta; Hap, Haptophyta; Ma, Malawimonas; Rhiz, Rhizaria; Rho, Rhodophyta; Stramen, Stramenopiles. OXPHOS, oxidative phosphorylation.

Figure 2.

Opposite trends in the cytonuclear movement of genes versus gene products. a | Schematic summary of the asymmetrical and opposite movement of genes versus gene products between cytoplasmic organelles and the nucleus during the history of cytonuclear integration. As described in the main text, non-adaptive ratchet-like processes related to functional gene-transfer and protein-import may contribute to these two asymmetries. b | Categorization of functional gene classes in the nucleus, highlighting the fact that not all cytoplasmically derived genes are targeted back to the mitochondria and plastids, and that not all nuclear genes with mitochondrial or plastid function originated from cytoplasmic genomes. Representative examples are provided for each category. OXPHOS, oxidative phosphorylation.

Figure 3.

Acquisition of supernumerary subunits in chimeric cytonuclear enzyme complexes. Subunits drawn with grey spheres are eukaryotic-specific (i.e., nuclear-encoded supernumerary subunits). Structures drawn with ribbons are ‘core’ subunits that were ancestrally present in bacteria. Red subunits correspond to genes that are still retained in cytoplasmic genomes, whereas yellow subunits correspond to genes that have been transferred to the nucleus. The same coloration is applied to homologous subunits in bacteria for the sake of comparison, even though there is no division into genomic compartments in bacteria. Subunits drawn with black ribbons in the cyanobacterial structure (PsaM and PsaX) have been lost from the eukaryotic structure. Complexes from both mitochondria and plastids were selected to illustrate the much more extensive recruitment of supernumerary subunits in mitochondria. Structures are based on the following Protein Data Bank (PDB) accessions. OXPHOS Complex I: Ovis aries (5LNK) and Thermus thermophilus (4HEA); Photosystem 1: Pisum sativum (4XK8) and Synechococcus elongatus (1JB0).