Life eternal in the face of senescence

Unlike prokaryotes, eukaryotes are born, mature, grow old, and die. Why death is inevitable for all complex life is among the most important questions in evolutionary biology. The mitochondrial theory of aging proposes that senescence is the process of depletion of viable mitochondria, which is an inevitable and unavoidable outcome of life processes. Mitonuclear interactions are proposed to play a key role in the evolution of the pace of life, and I review and discuss this emerging literature. Moreover, some eukaryotes, and most notably bilaterian animals, have a sequestered germ line that remains perpetually undifferentiated with no participation in organismal functions across generations. New hypotheses propose that germ lines enable intense selection on mt genomes thus preserving a mitochondrial template across generations. The implications of a mitonuclear perspective on aging and the evolution of germ lines are the focus of this chapter.

Forms and consequences of incompatibility

To understand the evolutionary consequences of poor coadaptation of mitochondrial and nuclear genes, it is necessary to consider in molecular detail the manifestations of mitochondrial dysfunction. Most considerations of mitochondrial dysfunction resulting from mitonuclear incompatibilities focus on protein–protein interactions in the electron transport system, but the interactions of mitochondrial and nuclear genes in enabling the transcription, translation, and replication of mitochondrial DNA can play an equally important role in mitonuclear coevolution and coadaptation. This chapter reviews the extensive literature on how mitochondrial dysfunction is the cause of many inherited human diseases and explains how this biomedical literature connects to a rapidly growing body of research on the evolution and maintenance of coadaptation of mitochondrial and nuclear genes among non-human eukaryotes. The goal of the chapter is to establish the fundamental importance of coadaptation between co-functioning mitochondrial and nuclear genes.

Epilogue

Evolutionary ecology is at the precipice of a paradigm shift. For many years and through the early years of the 21st century, mitochondrial genomes were dismissed as unimportant to the evolution of complex life. Variation within mitochondrial genomes was proposed to be functionally neutral. These conceptions about mitochondrial genomes and mitonuclear genomic interactions have begun to change within the past decade, but currently accepted theories of sexual selection and speciation were proposed before the discovery of the mitochondrial genome. Evolutionary ecology has yet to fully appreciate the fundamental implications of two genomes coding for the core respiratory enzymes of eukaryotes. This chapter promotes a fundamental rethinking of key theories in evolutionary ecology with full consideration of the necessity of coadaptation of mitochondrial and nuclear genes.

Mitonuclear mate choice

At each new generation, sexual reproduction creates new combinations of nuclear and mitochondrial genes, and the potential arises for mitonuclear incompatibilities and reduced fitness. Sexual selection plays a key role in maintaining mitonuclear coadaptation across generations because it enables pre-zygotic sorting for coadapted mitonuclear genotypes. In this chapter, I present data 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.

Adaptation and adaptive radiation

A key outcome of evolution by natural selection is adaptation. Since the beginning of the age of genetics, evolutionary biologists have focused on the evolution of nuclear genes as the basis for adaptation. Changes to the mitochondrial genome were long viewed as the result of drift and unimportant to organism fitness. New theory and empirical observations, however, are implicating changes in mitochondrial function as a central component of adaptation related to temperature, oxygen pressure, and diet. Novel mitochondrial function underlying adaptive evolution is a product of interacting mitochondrial and nuclear genes to create changes to the electron transport system, and variation in mitochondrial genotypes has been found to play a key role in such adaptive evolution of eukaryotes. Evidence is emerging that changes in mitochondrial function resulting from mitonuclear coevolution underlie key evolutionary innovations associated with major adaptive radiations including the transition from terrestrial locomotion to flight. I discuss the empirical evidence that supports a key role for mitonuclear coevolution in adaptation and adaptive radiation and the implications for fundamental ideas in ecology and evolution.

Coevolution, co-transmission, and conflict

Mitochondrial genes and nuclear genes are replicated and transmitted across generations as physically separated units. The extent to which these autonomous genomes are co-transmitted depends on the position of nuclear genes on autosomes versus sex chromosomes, and co-transmission has important implications for mitonuclear coevolution and conflict. Mitonuclear co-transmission, coadaptation, and coevolution are potentially very important for understanding fundamental evolutionary phenomena like Haldane’s rule. In addition, because mitochondrial genomes are transmitted strictly through maternal lines in most eukaryotes, selection on mitochondrial genes can favor female fitness over male fitness, leading to mother’s curse. The chapter assesses and draws conclusions about the relative importance of mitonuclear coadaptation and conflict in the evolution of eukaryotic lineages.

Compensatory coevolution

In most eukaryotes, mitochondrial genes mutate at a higher rate than nuclear genes. In addition, mitochondrial genes are transmitted without recombination, so slightly deleterious mutations are predicted to perpetually accumulate in mt genes. Accumulation of deleterious mutations in mt genes can potentially lead to loss of mitonuclear coadaptation. There is growing evidence that variant nuclear genes evolve so as to compensate for mitochondrial mutations and restore mitochondrial function. This is compensatory coevolution and is the focus of this chapter. The chapter also explores the idea that the many nuclear-encoded subunits in eukaryotic electron transport system enzymes were recruited to regulate and control the core catalytic reactions undertaken by the core mitochondrial subunits. It will also consider the evidence that when mutational erosion occurs, corrupted mitochondrial genotypes can be rescued by introgression of entire mitochondrial genomes. Compensatory coevolution has important implications for speciation, sexual selection, and adaptation.

Mitonuclear speciation

Current models of speciation assume that species arise when nuclear genotypes diverge following the disruption of gene flow between populations. This chapter explores the idea that speciation is specifically the result of divergence in coadapted mitonuclear gene complexes with divergence of most nuclear genes playing little or no role in speciation. To maintain mitonuclear coadaptation, nuclear genes must coevolve with rapidly changing mitochondrial genes. According to the mitonuclear compatibility concept of species, mitonuclear coevolution in isolated populations leads to speciation because population-specific mitonuclear coadaptations create between-population mitonuclear incompatibilities and hence barriers to gene flow between populations. In addition, selection for adaptive divergence of products of mitochondrial genes can lead to rapid fixation of novel mitochondrial genotypes between populations and consequently to disruption in gene flow between populations as the initiating step in animal speciation. The chapter considers the evidence for the involvement of mitonuclear compatibility in the process of speciation and the implications for this new concept of speciation and species.

The evolution of sex and two sexes

Sexual reproduction has proven so formidable a challenge for evolutionary biologists that it is commonly spoken of as “the paradox of sex.” Stated simply, individuals forsake one-half of their genetic representation in offspring by engaging in sexual versus asexual reproduction. There must be substantial benefits to compensate for so great a cost. Recent theory proposes that the primary benefit of sex is the tremendous diversity of genotypes produced via recombination during sexual reproduction that provides the raw material necessary to compensate for mutational erosion of mitochondrial genes. Another line of new thinking proposes that the reason that virtually all eukaryotes have two mating types rather than multiple mating types is that the existence of two mating types enables single mitochondrial genotypes to be vetted for compatibility with nuclear genotype. This chapter considers the implications and evidence for these new mitonuclear-based theories of key evolutionary ideas.

The genomic architecture of eukaryotes

Eukaryotes are chimeras—the product of an ancient fusion of a bacterium and an archaeon. Mitochondrial genomes only code for a few dozen products, so more than 1000 nuclear genes create most of the phenotype of a mitochondrion. Consequently, to produce a functional electron transport system and enable oxidative phosphorylation within an organism, every gene product of the mitochondrion must function in close association with products of the nuclear genome. This genomic architecture, with some mitochondrial autonomy, is proposed to be necessary to allow local regulation of the electron transport system within mitochondria. A two-genome architecture of eukaryotes sets up the fundamental necessity of mitonuclear coadaptation and has enormous implications for characteristics of complex life.