Damian K. Dowling

Reactive oxygen species as universal constraints in life-history evolution.

Evolutionary theory is firmly grounded on the existence of trade-offs between life-history traits, and recent interest has centred on the physiological mechanisms underlying such trade-offs. Several branches of evolutionary biology, particularly those focusing on ageing, immunological and sexual selection theory, have implicated reactive oxygen species (ROS) as profound evolutionary players. ROS are a highly reactive group of oxygen-containing molecules, generated as common by-products of vital oxidative enzyme complexes. Both animals and plants appear to intentionally harness ROS for use as molecular messengers to fulfil a wide range of essential biological processes. However, at high levels, ROS are known to exert very damaging effects through oxidative stress. For these reasons, ROS have been suggested to be important mediators of the cost of reproduction, and of trade-offs between metabolic rate and lifespan, and between immunity, sexual ornamentation and sperm quality. In this review, we integrate the above suggestions into one life-history framework, and review the evidence in support of the contention that ROS production will constitute a primary and universal constraint in life-history evolution.

Evolutionary implications of non-neutral mitochondrial genetic variation

Sequence variation in mitochondrial DNA (mtDNA) was traditionally considered to be selectively neutral. However, an accumulating body of evidence indicates that this assumption is invalid. Furthermore, recent advances indicate that mtDNA polymorphism can be maintained within populations via selection on the joint mitochondrial-nuclear genotype. Here, we review the latest findings that show mitochondrial and cytoplasmic genetic variation for life-history traits and fitness. We highlight the key importance of the mitochondrial-nuclear interaction as a unit of selection and discuss the consequences of mitochondrially encoded fitness effects on several key evolutionary processes. Our goal is to draw attention to the profound, yet neglected, influence of the mitochondrial genome on the fields of ecology and evolution.

Experimental Evidence Supports a Sex-Specific Selective Sieve in Mitochondrial Genome Evolution

Polymorphisms in the organelle genome have little effect in female flies but do alter gene expression in males. Mitochondria are maternally transmitted; hence, their genome can only make a direct and adaptive response to selection through females, whereas males represent an evolutionary dead end. In theory, this creates a sex-specific selective sieve, enabling deleterious mutations to accumulate in mitochondrial genomes if they exert male-specific effects. We tested this hypothesis, expressing five mitochondrial variants alongside a standard nuclear genome in Drosophila melanogaster, and found striking sexual asymmetry in patterns of nuclear gene expression. Mitochondrial polymorphism had few effects on nuclear gene expression in females but major effects in males, modifying nearly 10% of transcripts. These were mostly male-biased in expression, with enrichment hotspots in the testes and accessory glands. Our results suggest an evolutionary mechanism that results in mitochondrial genomes harboring male-specific mutation loads.

Mitochondria, Maternal Inheritance, and Male Aging

The maternal transmission of mitochondrial genomes invokes a sex-specific selective sieve, whereby mutations in mitochondrial DNA can only respond to selection acting directly on females. In theory, this enables male-harming mutations to accumulate in mitochondrial genomes when these same mutations are neutral, beneficial, or only slightly deleterious in their effects on females. Ultimately, this evolutionary process could result in the evolution of male-specific mitochondrial mutation loads; an idea previously termed Mothers Curse. Here, we present evidence that the effects of this process are broader than hitherto realized, and that it has resulted in mutation loads affecting patterns of aging in male, but not female Drosophila melanogaster. Furthermore, our results indicate that the mitochondrial mutation loads affecting male aging generally comprise numerous mutations over multiple sites. Our findings thus suggest that males are subject to dramatic consequences that result from the maternal transmission of mitochondrial genomes. They implicate the diminutive mitochondrial genome as a hotspot for mutations that affect sex-specific patterns of aging, thus promoting the idea that a sex-specific selective sieve in mitochondrial genome evolution is a contributing factor to sexual dimorphism in aging, commonly observed across species.

GENETIC ARCHITECTURE OF METABOLIC RATE: ENVIRONMENT SPECIFIC EPISTASIS BETWEEN MITOCHONDRIAL AND NUCLEAR GENES IN AN INSECT

The extent to which mitochondrial DNA (mtDNA) variation is involved in adaptive evolutionary change is currently being reevaluated. In particular, emerging evidence suggests that mtDNA genes coevolve with the nuclear genes with which they interact to form the energy producing enzyme complexes in the mitochondria. This suggests that intergenomic epistasis between mitochondrial and nuclear genes may affect whole‐organism metabolic phenotypes. Here, we use crossed combinations of mitochondrial and nuclear lineages of the seed beetle Callosobruchus maculatus and assay metabolic rate under two different temperature regimes. Metabolic rate was affected by an interaction between the mitochondrial and nuclear lineages and the temperature regime. Sequence data suggests that mitochondrial genetic variation has a role in determining the outcome of this interaction. Our genetic dissection of metabolic rate reveals a high level of complexity, encompassing genetic interactions over two genomes, and genotype × genotype × environment interactions. The evolutionary implications of these results are twofold. First, because metabolic rate is at the root of life histories, our results provide insights into the complexity of life‐history evolution in general, and thermal adaptation in particular. Second, our results suggest a mechanism that could contribute to the maintenance of nonneutral mtDNA polymorphism.

Mitochondrial Replacement, Evolution, and the Clinic

Mitochondrial replacement therapy might bear health risks, especially for males. Mitochondrial diseases [often caused by mutations in mitochondrial DNA (mtDNA)] can manifest in a range of severe symptoms, for which there are currently no cures (1). The diseases are passed from mothers to offspring. Intense research efforts have recently focused on a germline therapeutic strategy to prevent the inheritance of disease-causing mitochondria. However, although there has been increased government interest, especially in the United Kingdom, for using this approach to treat patients, there are reasons to believe that it is premature to move this technology into the clinic at this stage.

Intergenomic epistasis for fitness: within-population interactions between cytoplasmic and nuclear genes in Drosophila melanogaster.

The symbiotic relationship between the mitochondrial and nuclear genomes coordinates metabolic energy production and is fundamental to life among eukaryotes. Consequently, there is potential for strong selection to shape interactions between these two genomes. Substantial research attention has focused on the possibility that within-population sequence polymorphism in mitochondrial DNA (mtDNA) is maintained by mitonuclear fitness interactions. Early theory predicted that selection will often eliminate mitochondrial polymorphisms. However, recent models demonstrate that intergenomic interactions can promote the maintenance of polymorphism, especially if the nuclear genes involved are linked to the X chromosome. Most empirical studies to date that have assessed cytonuclear fitness interactions have studied variation across populations and it is still unclear how general and strong such interactions are within populations. We experimentally tested for cytonuclear interactions within a laboratory population of Drosophila melanogaster using 25 randomly sampled cytoplasmic genomes, expressed in three different haploid nuclear genetic backgrounds, while eliminating confounding effects of intracellular bacteria (e.g., Wolbachia). We found sizable cytonuclear fitness interactions within this population and present limited evidence suggesting that these effects were sex specific. Moreover, the relative fitness of cytonuclear genotypes was environment specific. Sequencing of mtDNA (2752 bp) revealed polymorphism within the population, suggesting that the observed cytoplasmic genetic effects may be mitochondrial in origin.

Mitonuclear interactions: evolutionary consequences over multiple biological scales

Fundamental biological processes hinge on coordinated interactions between genes spanning two obligate genomes—mitochondrial and nuclear. These interactions are key to complex life, and allelic variation that accumulates and persists at the loci embroiled in such intergenomic interactions should therefore be subjected to intense selection to maintain integrity of the mitochondrial electron transport system. Here, we compile evidence that suggests that mitochondrial–nuclear (mitonuclear) allelic interactions are evolutionarily significant modulators of the expression of key health-related and life-history phenotypes, across several biological scales—within species (intra- and interpopulational) and between species. We then introduce a new frontier for the study of mitonuclear interactions—those that occur within individuals, and are fuelled by the mtDNA heteroplasmy and the existence of nuclear-encoded mitochondrial gene duplicates and isoforms. Empirical evidence supports the idea of high-resolution tissue- and environment-specific modulation of intraindividual mitonuclear interactions. Predicting the penetrance, severity and expression patterns of mtDNA-induced mitochondrial diseases remains a conundrum. We contend that a deeper understanding of the dynamics and ramifications of mitonuclear interactions, across all biological levels, will provide key insights that tangibly advance our understanding, not only of core evolutionary processes, but also of the complex genetics underlying human mitochondrial disease.

Temperature-specific outcomes of cytoplasmic-nuclear interactions on egg-to-adult development time in seed beetles

Abstract The integration of the mitochondrial and nuclear genomes coordinates cellular energy production and is fundamental to life among eukaryotes. Therefore, there is potential for strong selection to shape the interactions between the two genomes. Several studies have now demonstrated that epistatic interactions between cytoplasmic and nuclear genes for fitness can occur both at a “within” and “across” population level. Genotype-by-environment interactions are common for traits that are encoded by nuclear genes, but the effects of environmental heterogeneity on traits that are partly encoded by cytoplasmic genes have received little attention despite the fact that there are reasons to believe that phenotypic effects of cytoplasmic genetic variation may often be environment specific. Consequently, the importance of environmental heterogeneity to the outcomes of cyto-nuclear fitness interactions and to the maintenance of mitochondrial polymorphism is unclear. Here, we assess the influence of temperature on cyto-nuclear effects on egg-to-adult development time in seed beetles (Callosobruchus maculatus). We employed an “across-population” design, sourcing beetles from five distinct populations and using backcrossing to create orthogonal combinations of distinct introgression lines, fixed for their cytoplasmic and nuclear lineages. We then assayed development times at two different temperatures and found sizeable cyto-nuclear effects in general, as well as temperature- and block-specific cyto-nuclear effects. These results demonstrate that environmental factors such as temperature do exert selection on cytoplasmic genes by favoring specific cyto-nuclear genetic combinations, and are consistent with the suggestion that complex genotype-by-environment interactions may promote the maintenance of polymorphism in mitochondrial genes.

Effects of cytoplasmic genes on sperm viability and sperm morphology in a seed beetle: implications for sperm competition theory?

Sperm competition theory predicts that sperm traits influencing male fertilizing ability will evolve adaptively. However, it has been suggested that some sperm traits may be at least partly encoded by mitochondrial genes. If true, this may constrain the adaptive evolution of such traits because mitochondrial DNA (mtDNA) is maternally inherited and there is thus no selection on mtDNA in males. Phenotypic variation in such traits may nevertheless be high because mutations in mtDNA that have deleterious effects on male traits, but neutral or beneficial effects in females, may be maintained by random processes or selection in females. We used backcrossing to create introgression lines of seed beetles (Callosobruchus maculatus), carrying orthogonal combinations of distinct lineages of cytoplasmic and nuclear genes, and then assayed sperm viability and sperm length in all lines. We found sizeable cytoplasmic effects on both sperm traits and our analyses also suggested that the cytoplasmic effects varied across nuclear genetic backgrounds. We discuss some potential implications of these findings for sperm competition theory.