Parallel Structural Evolution of Mitochondrial Ribosomes and OXPHOS Complexes

Abstract

The five macromolecular complexes that jointly mediate oxidative phosphorylation (OXPHOS) in mitochondria consist of many more subunits than those of bacteria, yet, it remains unclear by which evolutionary mechanism(s) these novel subunits were recruited. Even less well understood is the structural evolution of mitochondrial ribosomes (mitoribosomes): while it was long thought that their exceptionally high protein content would physically compensate for their uniquely low amount of ribosomal RNA (rRNA), this hypothesis has been refuted by structural studies. Here, we present a cryo-electron microscopy structure of the 73S mitoribosome from Neurospora crassa, together with genomic and proteomic analyses of mitoribosome composition across the eukaryotic domain. Surprisingly, our findings reveal that both structurally and compositionally, mitoribosomes have evolved very similarly to mitochondrial OXPHOS complexes via two distinct phases: A constructive phase that mainly acted early in eukaryote evolution, resulting in the recruitment of altogether approximately 75 novel subunits, and a reductive phase that acted during metazoan evolution, resulting in gradual length-reduction of mitochondrially encoded rRNAs and OXPHOS proteins. Both phases can be well explained by the accumulation of (slightly) deleterious mutations and deletions, respectively, in mitochondrially encoded rRNAs and OXPHOS proteins. We argue that the main role of the newly recruited (nuclear encoded) ribosomal- and OXPHOS proteins is to provide structural compensation to the mutationally destabilized mitochondrially encoded components. While the newly recruited proteins probably provide a selective advantage owing to their compensatory nature, and while their presence may have opened evolutionary pathways toward novel mitochondrion-specific functions, we emphasize that the initial events that resulted in their recruitment was nonadaptive in nature. Our framework is supported by population genetic studies, and it can explain the complete structural evolution of mitochondrial ribosomes and OXPHOS complexes, as well as many observed functions of individual proteins.

Mitonuclear coevolution as the genesis of speciation and the mitochondrial DNA barcode gap

“…2015; van der Sluis et al. 2015). mt genes can also potentially compensate for changes in deleterious changes in N‐mt genes.…”

“…As a consequence, slightly deleterious mutations perpetually accumulate in the mitochondrial genome (Lynch and Blanchard 1998;Neiman and Taylor 2009), and because all mitochondrial genes code for OXPHOS function, an accumulation of deleterious mutations in the mitochondrial genome erodes OXPHOS function resulting in loss of fitness (Wallace 2010). Growing evidence suggests that N-mt genes can evolve so as to compensate for the deleterious effects of mutations in mt genes, thereby reversing deterioration of OXPHOS (Mishmar et al 2006;Barreto and Burton 2013;Havird et al 2015;van der Sluis et al 2015). mt genes can also potentially compensate for changes in deleterious changes in N-mt genes.…”

Conservative and compensatory evolution in oxidative phosphorylation complexes of angiosperms with highly divergent rates of mitochondrial genome evolution

“…It has also been proposed that the recruitment of novel nuclear‐encoded OXPHOS subunits in eukaryotes may have been a form of structural compensation for the unstable mitochondrial‐encoded subunits (van der Sluis et al. ).…”

Mitonuclear Mate Choice: A Missing Component of Sexual Selection Theory?

“…Species‐specificity of mitonuclear coadaptation results primarily from the need to maintain coadaptation in the face of accumulation of deleterious mutations in the mitochondrial genome . Evidence suggests that N‐mt genes can evolve so as to compensate for the deleterious effects of mutations in mt genes, thereby preventing deterioration of OXPHOS . Such compensatory coevolution appears to occur not only in the protein‐protein interactions of the ETS, but also in the protein‐DNA interactions during replication of the mt genome, in protein‐RNA interactions in mitochondrial ribosomes, and between mt‐tRNAs and aminoacyl tRNA synthetase .…”

“…Evidence suggests that N‐mt genes can evolve so as to compensate for the deleterious effects of mutations in mt genes, thereby preventing deterioration of OXPHOS . Such compensatory coevolution appears to occur not only in the protein‐protein interactions of the ETS, but also in the protein‐DNA interactions during replication of the mt genome, in protein‐RNA interactions in mitochondrial ribosomes, and between mt‐tRNAs and aminoacyl tRNA synthetase . Coevolution between mitochondrial and nuclear genomes – in which N‐mt genes compensate for random deleterious mutations in mt genes – can potentially lead to perpetual and unpredictable divergence in tightly coadapted complexes of mt and N‐mt genes within species .…”