The study of reproductive isolation and species barriers frequently focuses on mitochondrial genomes and has produced two alternative and almost diametrically opposed narratives. On one hand, mtDNA may be at the forefront of speciation events, with co-evolved mitonuclear interactions responsible for some of the earliest genetic incompatibilities arising among isolated populations. On the other hand, there are numerous cases of introgression of mtDNA across species boundaries even when nuclear gene flow is restricted. We argue that these seemingly contradictory patterns can result from a single underlying cause. Specifically, the accumulation of deleterious mutations in mtDNA creates a problem with two alternative evolutionary solutions. In some cases, compensatory or epistatic changes in the nuclear genome may ameliorate the effects of mitochondrial mutations, thereby establishing coadapted mitonuclear genotypes within populations and forming the basis of reproductive incompatibilities between populations. Alternatively, populations with high mitochondrial mutation loads may be rescued by replacement with a more fit, foreign mitochondrial haplotype. Coupled with many nonadaptive mechanisms of introgression that can preferentially affect cytoplasmic genomes, this form of adaptive introgression may contribute to the widespread discordance between mitochondrial and nuclear genealogies. Here, we review recent advances related to mitochondrial introgression and mitonuclear incompatibilities, including the potential for cointrogression of mtDNA and interacting nuclear genes. We also address an emerging controversy over the classic assumption that selection on mitochondrial genomes is inefficient and discuss the mechanisms that lead lineages down alternative evolutionary paths in response to mitochondrial mutation accumulation.

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.

Complex life exists only with a continuous and rich supply of energy from oxidative phosphorylation in mitochondria. The biochemical machinery that enables the majority of energy production in eukaryotes is encoded by both mitochondrial and nuclear genes so the products of these genomes must interact closely to achieve coordinated function of core respiratory processes. It follows that selection for efficient respiration will lead to selection on optimal combinations of mitochondrial and nuclear genotypes, facilitating mitonuclear coadaptation. In this essay, we outline the modes by which mitochondrial and nuclear genomes coevolve within natural populations, and discuss the implications of mitonuclear coadaptation for diverse fields of study in the biological sciences. We identify six themes in the study of mitonuclear interactions, developed through decades of research, which provide a roadmap for both ecological and biomedical studies seeking to elucidate the contribution of intergenomic coevolution to the genetics of natural populations.

Rates of sequence evolution in plastid genomes are generally low, but numerous angiosperm lineages exhibit accelerated evolutionary rates in similar subsets of plastid genes. These genes include clpP1 and accD, which encode components of the caseinolytic protease (CLP) and acetyl-coA carboxylase (ACCase) complexes, respectively. Whether these extreme and repeated accelerations in rates of plastid genome evolution result from adaptive change in proteins (i.e., positive selection) or simply a loss of functional constraint (i.e., relaxed purifying selection) is a source of ongoing controversy. To address this, we have taken advantage of the multiple independent accelerations that have occurred within the genus Silene (Caryophyllaceae) by examining phylogenetic and population genetic variation in the nuclear genes that encode subunits of the CLP and ACCase complexes. We found that, in species with accelerated plastid genome evolution, the nuclear-encoded subunits in the CLP and ACCase complexes are also evolving rapidly, especially those involved in direct physical interactions with plastid-encoded proteins. A massive excess of nonsynonymous substitutions between species relative to levels of intraspecific polymorphism indicated a history of strong positive selection (particularly in CLP genes). Interestingly, however, some species are likely undergoing loss of the native (heteromeric) plastid ACCase and putative functional replacement by a duplicated cytosolic (homomeric) ACCase. Overall, the patterns of molecular evolution in these plastidnuclear complexes are unusual for anciently conserved enzymes. They instead resemble cases of antagonistic coevolution between pathogens and host immune genes. We discuss a possible role of plastid-nuclear conflict as a novel cause of accelerated evolution.

Eukaryotes rely on proteins encoded by the nuclear and mitochondrial (mt) genomes, which interact within multisubunit complexes such as oxidative-phosphorylation enzymes. Although selection is thought to be less efficient on the asexual mt genome, in bilaterian animals the ratio of nonsynonymous to synonymous substitutions (x) is lower in mt-compared with nuclear-encoded OXPHOS subunits, suggesting stronger effects of purifying selection in the mt genome. Because high levels of gene expression constrain protein sequence evolution, one proposed resolution to this paradox is that mt genes are expressed more highly than nuclear genes. To test this hypothesis, we investigated expression and sequence evolution of mt and nuclear genes from 84 diverse eukaryotes that vary in mt gene content and mutation rate. We found that the relationship between mt and nuclear x values varied dramatically across eukaryotes. In contrast, transcript abundance is consistently higher for mt genes than nuclear genes, regardless of which genes happen to be in the mt genome. Consequently, expression levels cannot be responsible for the differences in x. Rather, 84% of the variance in the ratio of x values between mt and nuclear genes could be explained by differences in mutation rate between the two genomes. We relate these findings to the hypothesis that high rates of mt mutation select for compensatory changes in the nuclear genome. We also propose an explanation for why mt transcripts consistently outnumber their nuclear counterparts, with implications for mitonuclear protein imbalance and aging.

1. Characterizing thermal acclimation is a common goal of eco-physiological studies and has important implications for models of climate change and environmental adaptation. However, quantifying thermal acclimation in biological rate processes is not straightforward because many rates increase with temperature due to the acute effect of thermodynamics on molecular interactions. Disentangling such passive plastic responses from active acclimation responses is critical for describing patterns of thermal acclimation.2. Here, we reviewed published studies and distinguished between different study designs measuring the acute (i.e. passive) and acclimated (i.e. active) effects of temperature on metabolic rate. We then developed a method to quantify and classify acclimation responses by comparing acute and acclimated Q 10 values. Finally, we applied this method using meta-analysis to characterize thermal acclimation in metabolic rates of ectothermic animals.3. We reviewed 258 studies measuring thermal effects on metabolic rates, and found that a majority of these studies (74%) did not allow for quantifying the independent effects of acclimation. Such studies were more common when testing aquatic taxa and continue to be published even in recent years. 4.A meta-analysis of 96 studies where acclimation could be quantified (using 1,072 Q 10 values) revealed that 'partial compensation' was the most common acclimation response (i.e. acclimation tended to offset the passive change in metabolic rate due to acute temperature changes). However, 'no acclimation' and 'inverse compensation', in which acclimation further augmented the acute change in metabolic rate, were also common. 5. Acclimation responses differed among taxa, habitats and with experimental design. Amphibians and other terrestrial taxa tended to show weak acclimation responses, whereas fishes and other aquatic taxa tended to show stronger compensatory responses. Increasing how long the animal was allowed to adjust to a new test temperature increased the acclimation response, but body size did not.Acclimation responses were also stronger with longer acclimation durations.

Interactions between nuclear and mitochondrial gene products are critical for eukaryotic cell function. Nuclear genes encoding mitochondrial-targeted proteins (N-mt genes) experience elevated rates of evolution, which has often been interpreted as evidence of nuclear compensation in response to elevated mitochondrial mutation rates. However, N-mt genes may be under relaxed functional constraints, which could also explain observed increases in their evolutionary rate. To disentangle these hypotheses, we examined patterns of sequence and structural evolution in nuclear and mitochondrial-encoded oxidative phosphorylation proteins from species in the angiosperm genus Silene with vastly different mitochondrial mutation rates. We found correlated increases in N-mt gene evolution in species with fast-evolving mitochondrial DNA. Structural modeling revealed an overrepresentation of N-mt substitutions at positions that directly contact mutated residues in mitochondrial-encoded proteins, despite overall patterns of conservative structural evolution. These findings support the hypothesis that selection for compensatory changes in response to mitochondrial mutations contributes to the elevated rate of evolution in N-mt genes. We discuss these results in light of theories implicating mitochondrial mutation rates and mitonuclear co-evolution as drivers of speciation and suggest comparative and experimental approaches that could take advantage of heterogeneity in rates of mtDNA evolution across eukaryotes to evaluate such theories.

Mitochondria, a nearly ubiquitous feature of eukaryotes, are derived from an ancient symbiosis. Despite billions of years of cooperative coevolution -in what is arguably the most important mutualism in the history of life -the persistence of mitochondrial genomes also creates conditions for genetic conflict with the nucleus. Because mitochondrial genomes are present in numerous copies per cell, they are subject to both within-and among-organism levels of selection. Accordingly, 'selfish' genotypes that increase their own proliferation can rise to high frequencies even if they decrease organismal fitness. It has been argued that uniparental (often maternal) inheritance of cytoplasmic genomes evolved to curtail such selfish replication by minimizing within-individual variation and, hence, within-individual selection. However, uniparental inheritance creates conditions for cytonuclear conflict over sex determination and sex ratio, as well as conditions for sexual antagonism when mitochondrial variants increase transmission by enhancing maternal fitness but have the side-effect of being harmful to males (i.e., 'mother's curse'). Here, we review recent advances in understanding selfish replication and sexual antagonism in the evolution of mitochondrial genomes and the mechanisms that suppress selfish interactions, drawing parallels and contrasts with other organelles (plastids) and bacterial endosymbionts that arose more recently. Although cytonuclear conflict is widespread across eukaryotes, it can be cryptic due to nuclear suppression, highly variable, and lineage-specific, reflecting the diverse biology of eukaryotes and the varying architectures of their cytoplasmic genomes.