Eukaryotic origins are heavily debated. The author as well as others have proposed that they are inextricably linked with the arrival of a pre‐mitochondrion of alphaproteobacterial‐like ancestry, in a so‐called symbiogenic scenario. The ensuing mutual adaptation of archaeal host and endosymbiont seems to have been a defining influence during the processes leading to the last eukaryotic common ancestor. An unresolved question in this scenario deals with the means by which the bacterium ends up inside. Older hypotheses revolve around the application (...) of known antagonistic interactions, the bacterium being prey or parasite. Here, in reviewing the field, the author argues that such models share flaws, hence making them less likely, and that a “pre‐symbiotic stage” would have eased ongoing metabolic integration. Based on this the author will speculate about the nature of the (endo) symbiosis that started eukaryotic evolution–in the context of bacterial entry being a relatively “early” event–and stress the differences between this uptake and subsequent ones. He will also briefly discuss how the mutual adaptation following the merger progressed and how many eukaryotic hallmarks can be understood in light of coadaptation. Also see the video abstract here https://youtu.be/ekqtNleVJpU. (shrink)

The fitness of a eukaryote hinges on the coordinated function of the products of its nuclear and mitochondrial genomes in achieving oxidative phosphorylation. I propose that sexual selection plays a key role in the maintenance of mitonuclear coadaptation across generations because it enables pre-zygotic sorting for coadapted mitonuclear genotypes. At each new generation, sexual reproduction creates new combinations of nuclear and mitochondrial genes, and the potential arises for mitonuclear incompatibilities and reduced fitness. In reviewing the literature, I hypothesize that individuals (...) engaged in mate choice select partners with correct species-typical mitochondrial and nuclear genotypes as well as individuals with highly functional cellular respiration. The implication is that mate choice for compatible nuclear and mitochondrial genes can play a significant role in generating the patterns of ornamentation and preferences observed in animals. A number of testable predictions emerge from this mitonuclear compatibility hypothesis of sexual selection. Products of mitochondrial and nuclear genes co-function to enable cellular respiration, so it is critical that compatible mitochondrial and nuclear genes be matched each generation. I propose that a core function of mate choice is selection for mitochondrial and nuclear genes that create compatible and functional combinations in offspring. (shrink)

The evolution of sex in eukaryotes represents a paradox, given the “twofold” fitness cost it incurs. We hypothesize that the mutational dynamics of the mitochondrial genome would have favored the evolution of sexual reproduction. Mitochondrial DNA (mtDNA) exhibits a high‐mutation rate across most eukaryote taxa, and several lines of evidence suggest that this high rate is an ancestral character. This seems inexplicable given that mtDNA‐encoded genes underlie the expression of life's most salient functions, including energy conversion. We propose that negative (...) metabolic effects linked to mitochondrial mutation accumulation would have invoked selection for sexual recombination between divergent host nuclear genomes in early eukaryote lineages. This would provide a mechanism by which recombinant host genotypes could be rapidly shuffled and screened for the presence of compensatory modifiers that offset mtDNA‐induced harm. Under this hypothesis, recombination provides the genetic variation necessary for compensatory nuclear coadaptation to keep pace with mitochondrial mutation accumulation. (shrink)

Mitochondria exist in large numbers per cell. Therefore, the strength of natural selection on individual mtDNAs for their contribution to cellular fitness is weak whereas the strength of selection in favor of mtDNAs that increase their own replication without regard for cellular functions is strong. This problem has been solved for most mitochondrial genes by their transfer to the nucleus but a few critical genes remain encoded by mtDNA. Organisms manage the evolution of mtDNA to prevent mutational decay of essential (...) services mitochondria provide to their hosts. Bottlenecks of mitochondrial numbers in female germlines increase the homogeneity of mtDNAs within cells and allow intraorganismal selection to eliminate cells with low quality mitochondria. Mechanisms of intracellular “quality control” allow direct selection on the competence of individual mtDNAs. These processes maintain the integrity of mtDNAs within the germline but are inadequate to indefinitely maintain mitochondrial function in somatic cells. (shrink)

Why the DNA‐containing organelles, chloroplasts, and mitochondria, are inherited maternally is a long standing and unsolved question. However, recent years have seen a paradigm shift, in that the absoluteness of uniparental inheritance is increasingly questioned. Here, we review the field and propose a unifying model for organelle inheritance. We argue that the predominance of the maternal mode is a result of higher mutational load in the paternal gamete. Uniparental inheritance evolved from relaxed organelle inheritance patterns because it avoids the spread (...) of selfish cytoplasmic elements. However, on evolutionary timescales, uniparentally inherited organelles are susceptible to mutational meltdown (Muller's ratchet). To prevent this, fall‐back to relaxed inheritance patterns occurs, allowing low levels of sexual organelle recombination. Since sexual organelle recombination is insufficient to mitigate the effects of selfish cytoplasmic elements, various mechanisms for uniparental inheritance then evolve again independently. Organelle inheritance must therefore be seen as an evolutionary unstable trait, with a strong general bias to the uniparental, maternal, mode. (shrink)

No overarching hypotheses tie the basic mechanisms of mitochondrial reactive oxygen species (ROS) production to activity dependent synapse pruning—a fundamental biological process in health and disease. Neuronal activity divergently regulates mitochondrial ROS: activity decreases whereas inactivity increases their production, respectively. Placing mitochondrial ROS as innate synaptic activity sentinels informs the novel hypothesis that: (1) at an inactive synapse, increased mitochondrial ROS production initiates intrinsic apoptosis dependent pruning; and (2) at an active synapse, decreased mitochondrial ROS production masks intrinsic apoptosis dependent (...) pruning. Immature antioxidant defense may enable the developing brain to harness mitochondrial ROS to prune weak synapses. Beyond development, endogenous antioxidant defense constrains mitochondrial (ROS) to mask pruning. Unwanted age‐related synapse loss may arise when mitochondrial ROS aberrantly recapitulate developmental pruning. Placing mitochondrial ROS with their hands on the shears is beneficial in early but deleterious in later life. (shrink)

Mitochondria are increasingly being recognized as information hubs that sense cellular changes and transmit messages to other cellular components, such as the nucleus, the endoplasmic reticulum (ER), the Golgi apparatus, and lysosomes. Nonetheless, the interaction between mitochondria and the nucleus is of special interest because they both host part of the cellular genome. Thus, the communication between genome‐bearing organelles would likely include gene expression regulation. Multiple nuclear‐encoded proteins have been known to regulate mitochondrial gene expression. On the contrary, no mitochondrial‐encoded (...) factors are known to actively regulate nuclear gene expression. MOTS‐c (mitochondrial open reading frame of the 12S ribosomal RNA type‐c) is a recently identified peptide encoded within the mitochondrial 12S ribosomal RNA gene that has metabolic functions. Notably, MOTS‐c can translocate to the nucleus upon metabolic stress (e.g., glucose restriction and oxidative stress) and directly regulate adaptive nuclear gene expression to promote cellular homeostasis. It is hypothesized that cellular fitness requires the coevolved mitonuclear genomes to coordinate adaptive responses using gene‐encoded factors that cross‐regulate the opposite genome. This suggests that cellular gene expression requires the bipartite split genomes to operate as a unified system, rather than the nucleus being the sole master regulator. (shrink)