How is mitochondria related to evolution?

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M Tobler,

Division of Biology, Kansas State University, Manhattan, KS 66506, USA

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From the symposium “Beyond the powerhouse: integrating mitonuclear evolution, physiology, and theory in comparative biology” presented at the annual meeting of the Society of Integrative and Comparative Biology, January 3–7, 2019 at Tampa, Florida.

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  M Tobler, N Barts, R Greenway, Mitochondria and the Origin of Species: Bridging Genetic and Ecological Perspectives on Speciation Processes, Integrative and Comparative Biology, Volume 59, Issue 4, October 2019, Pages 900–911, https://doi.org/10.1093/icb/icz025

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Abstract

Introduction

Elucidating the mechanisms by which new species arise remains a major research focus in biology (Wolf et al. 2010; Marie Curie Speciation Network 2012; Nosil 2012). Mitochondria have long been hypothesized to play a role in speciation processes, because break-up of co-adapted gene complexes encoded in the mitochondrial and nuclear genomes during hybridization can lead to intrinsic postzygotic incompatibilities (Burton et al. 2013). In addition, there is increasing evidence that adaptive processes shape mitochondrial evolution, and adaptive divergence of mitochondrial function can potentially be connected to a wide variety of pre- and postzygotic isolating mechanisms. In this review, we first provide an overview of the diverse ways mitochondrial evolution may be linked to animal diversification, embracing some of the enthusiasm surrounding mitochondrial perspectives on speciation processes (Gershoni et al. 2009; Hill 2016). We also highlight some critical gaps in our knowledge and propose avenues for future research to better understand the roles mitochondria might play in speciation. Addressing these knowledge gaps has the potential to integrate genetic and ecological views of speciation.

Different perspectives on speciation

Although Darwin introduced natural selection as the major creative force in biological diversification (Darwin 1859), speciation was long thought to be a consequence of random processes that give rise to genetic incompatibilities (Dobzhansky 1937; Muller 1942). The idea was that genetic drift would fix alternative alleles at multiple loci when populations are geographically isolated, ultimately causing detrimental epistatic effects when alternative alleles at different loci are recombined during interpopulation hybridization upon secondary contact (allopatric speciation model; Mayr 1963; Templeton 1980). However, our notion of the speciation process has dramatically changed in recent decades. Most frameworks now focus on understanding how the interplay among natural selection, genetic drift, and gene flow shapes population divergence and what mechanisms give rise to reproductive isolation (Schluter 2001, 2009; Marie Curie Speciation Network 2012; Nosil 2012). We learned that natural selection often plays a critical role in driving population divergence even when populations are not geographically isolated, and that reproductive isolation—mediated by a variety of pre- and postzygotic mechanisms—can emerge as a by-product of adaptation (ecological speciation; Schluter 2000, 2001; Via 2002; Rundle and Nosil 2005; Nosil 2012). Intriguingly, our knowledge about the role of intrinsic incompatibilities during speciation with gene flow remains largely unknown (Kulmuni and Westram 2017), even though this mechanism has been a focus of speciation research (Orr and Presgraves 2000; Presgraves 2010), and theory and experiments have indicated that divergent selection can drive the evolution of such incompatibilities (Gavrilets 2004; Anderson et al. 2010).

This knowledge gap is in part caused by two different research approaches, each perhaps facilitating inquiry about speciation processes and reproductive isolation in particular study systems. The genetic lens on speciation has been particularly amendable to studying laboratory models, leading to the identification of genes that are under positive selection and mediate reproductive isolation through the generation of genetic incompatibilities among lineages (Greenberg et al. 2003; Presgraves et al. 2003; Orr 2005). While the molecular signatures of nucleotide substitutions can bear the indelible mark of natural selection, the ecological context and sources of selection acting on these genes have remained elusive. Furthermore, the identification of putative speciation genes often occurs in divergent lineages that have been separated for millions of years (Maheshwari and Barbash 2011), and it remains unclear whether incompatibilities arose during speciation, or whether they accumulated after speciation had been completed by other means. In contrast, the ecological lens on speciation has primarily focused on natural study systems and identified the phenotypic traits shaped by divergent selection that are involved in mediating reproductive isolation. Such studies have identified both pre- and postzygotic mechanisms of reproductive isolation that arose from different selective forces often occurring in a replicated fashion, leading to parallel speciation (Rundle et al. 2000; Johannesson 2001; McKinnon et al. 2004; Langerhans et al. 2007; Butlin et al. 2008; Nosil et al. 2008). However, identifying the genetic mechanisms underlying adaptive traits and reproductive isolation has been challenging in natural systems (Wolf et al. 2010; Marie Curie Speciation Network 2012). While the two approaches have yielded complementary insights, understanding the mechanistic links between selection (and other evolutionary forces), genomic divergence, and the functional consequences that mediate reproductive isolation remains a critical gap in our understanding of the speciation process (Schluter 2009; Wolf et al. 2010; Byers et al. 2017). Ideally, we aim to understand how selection shapes genetic changes that mediate adaptive modifications of biochemical properties and physiological processes that govern organismal function (Barrett and Hoekstra 2011), and how the resulting functional differences among diverging populations create incompatibilities and mediate reproductive isolation (Marie Curie Speciation Network 2012). Here, we argue that a mitochondrial perspective on speciation might facilitate the exploration of causal links between genotypes, phenotypes, and the fitness of organisms in their natural environment, ultimately addressing gaps in our mechanistic understanding of the speciation process.

Mitochondria: not just the powerhouse of the cell …

The oxidative phosphorylation pathway (OxPhos) in mitochondria is the major source of ATP production in eukaryotic cells (Nunnari and Suomalainen 2012; Friedman and Nunnari 2014); hence, mitochondria are known as the powerhouse of the cell. Proper function of OxPhos is dependent on the interaction of two genomes inherent to eukaryotes, as multiple protein complexes in the pathway are composed of gene products from both the mitochondrial and nuclear genomes (Woodson and Chory 2008). Mitochondrial and nuclear gene products also interact in the transcription and translation of mitochondrial genes required for the assembly of OxPhos components (Taanman 1999; D’Souza and Minczuk 2018). The function of “the powerhouse,” however, is not restricted to aerobic ATP production. Mitochondria are also involved in the regulation of cellular redox and calcium balance, amino acid and lipid metabolism, and cell death (Galluzzi et al. 2012; Nunnari and Suomalainen 2012; Quirós et al. 2016; Vakifahmetoglu-Norberg et al. 2017).

The proper function of eukaryotic cells is consequently dependent on close interactions between gene products associated with multiple loci that exhibit different patterns of inheritance. Mitochondrial genes are typically present on a single chromosome (but see Nosek et al. 1998) and inherited maternally (but see Luo et al. 2018). Nuclear genes involved in mitochondrial function are distributed across multiple linkage groups, and alleles at different loci are recombined in every generation in sexually reproducing organisms. This is interesting from an evolutionary perspective, because the dependency of mitochondrial function is contingent on the coevolution of mitochondrial and nuclear genes (Rand et al. 2004; Levin et al. 2014; van der Sluis et al. 2015). Since mutation rates are higher in the mitochondrial genome (Lynch and Blanchard 1998; Neiman and Taylor 2009; Havird and Sloan 2016), we would expect compensatory mutations in corresponding nuclear genes involved in mitochondrial function (Osada and Akashi 2012; Havird et al. 2015). More importantly, break-up of co-adapted alleles during hybridization should lead to so called mito-nuclear incompatibilities, where recombination of divergent alleles encoded in mitochondrial and nuclear genomes causes reduced fitness in hybrids irrespective of the environmental context (Burton et al. 2013). These are exactly the kind of intrinsic incompatibilities that have been the focus of genetic perspectives of speciation processes (i.e., they are a case of Dobzhansky–Muller incompatibilities), and there is clear evidence that mitochondrially mediated intrinsic incompatibilities lead to decreases in viability and fertility in natural systems (e.g., Barreto and Burton 2013; Burton et al. 2006; Rand et al. 2006; Ellison et al. 2008; Gibson et al. 2013; Zhang et al. 2017; Haddad et al. 2018). A major unresolved question is how mitochondrial evolution and mito-nuclear incompatibilities fit into ecological perspectives of speciation processes.

The role of mitochondria in adaptation and reproductive isolation

Historically, the evolution of mitochondrial genomes was assumed to be governed by neutral processes (Ballard and Kreitman 1995). However, evidence has been mounting over the past decades that genetic variation in mitochondria is shaped by selection and impacts organismal fitness (Blier et al. 2001; Rand 2001; Bazin et al. 2006; Meiklejohn et al. 2007; Dowling et al. 2008; Hill et al. 2018). Mitochondrial adaptation has been inferred through analyses of molecular evolution, as well as assays of physiological function at the level of molecules, organelles, cells, and organisms, providing insights about the role of mitochondria in adaptation to environmental stress (Sokolova 2018), variation in temperature and other climatic variables (Dahlhoff et al. 1991; Silva et al. 2014; Camus et al. 2017; Lasne et al. 2019), altitude and hypoxia (Scott et al. 2011; Gu et al. 2012; Zhang et al. 2013), as well as the extreme aerobic demands of flight and high speed swimming (Shen et al. 2010; Li et al. 2018; Zhang and Broughton 2015). Hence, coevolution between genomes does not have to be a consequence of accumulations of deleterious mutations in mitochondrial genomes and compensatory mutations in nuclear genomes; instead, evolution of mitochondrial function may be governed by adaptive processes (see James et al. 2016 and Hill et al. 2018 for reviews). Moreover, adaptive evolution of mitochondrial function does not necessarily lead to co-evolution of mitochondrial and nuclear genes (Montooth et al. 2010; Adrion et al. 2016; Mossman et al. 2016). Ecological speciation frameworks suggest that adaptive evolution of mitochondria can lead to the emergence of reproductive isolation as a byproduct, even if there is no co-evolution between the mitochondrial and nuclear genomes.

Mitochondrial adaptation and postzygotic reproductive isolation

As already discussed, there is clear evidence for intrinsic incompatibilities mediated by mitochondria. The question of whether these examples fit into an ecological speciation framework primarily depends on what mechanisms caused co-evolutionary divergence in mitochondrial and nuclear genes in lineages undergoing speciation. Mito-nuclear incompatibilities fit ecological speciation frameworks if such incompatibilities arise through divergent selection on mitochondrial function mediating adaptation to different environmental conditions. Research investigating mechanisms of adaptation and reproductive isolation in Fundulus heteroclitus killifish subspecies provides evidence of this scenario. Southern and northern F. heteroclitus populations show adaptive divergence in mitochondrial function and plasticity across temperature gradients (Chung and Schulte 2015; Healy et al. 2017; Bryant et al. 2018). Additionally, there is evidence for increased heterozygote deficit and mito-nuclear disequilibrium in populations located in hybrid zones, and steep clines were detected in a nuclear-encoded mitochondrial gene and several nuclear genes associated with oxidative metabolism (McKenzie et al. 2015, 2017, 2016; Baris et al. 2017). These data suggest that epistatic interactions in mito-nuclear complexes arising from selection may be limiting the success of hybrids and contributing to reproductive isolation.

Under ecological speciation scenarios, postzygotic reproductive isolation may not only be mediated through intrinsic incompatibilities. In cases where hybrids are perfectly viable and fertile, postzygotic isolation may be extrinsic and contingent on ecological sources of selection. There is growing evidence that epistatic effects between mitochondrial and nuclear loci in Drosophila are dependent on temperature and resource availability (Hoekstra et al. 2013, 2018; Mossman et al. 2016). In addition, climate-dependent mito-nuclear interactions have been suspected to negatively impact hybrid nestling growth and hybrid male metabolic rates in Ficedula flycatchers, contributing to reproductive isolation between sister species (Qvarnström et al. 2016; McFarlane et al. 2016).

An open question remains whether extrinsic incompatibilities truly require mito-nuclear co-evolution. It has previously been assumed that adaptive divergence in a mitochondrial gene inevitably entails co-evolution with corresponding nuclear genes (Hill 2016). However, adaptive modification of OxPhos can be mediated by few amino acid substitutions in mitochondrial genes (Scott et al. 2011; Pfenninger et al. 2014). If adaptive amino acid substitutions in relevant proteins occur either in the mitochondrial or the nuclear genomes, hybrids should theoretically incur a fitness cost when their genotype is misaligned with environmental conditions. Generally, the evidence for context-dependent epistatic interactions (Hoekstra et al. 2013; Gebiola et al. 2016) and mitochondrial adaptation (Scott et al. 2011; Pfenninger et al. 2014) should incentivize the examination of ecologically-dependent mitochondrial dysfunction in hybrids in cases where experiments have failed to reveal intrinsic incompatibilities despite evidence for selection on genes associated with mitochondrial function.

Mitochondrial adaptation and prezygotic reproductive isolation

In ecological speciation scenarios, new species may arise in the absence of intrinsic or extrinsic postzygotic isolation if divergent selection prevents the formation of hybrids to begin with. Such prezygotic reproductive isolation may be a simple consequence of local adaptation to divergent habitats, where genotypes adapted to one environment prefer that environment or are selected against in another (Nosil et al. 2005; Rundle and Nosil 2005). Habitat preferences and selection against immigrants reduce the likelihood of encounters between potential mates adapted to different environmental conditions, reducing gene flow among populations even when there is no co-evolution between mitochondrial and nuclear genomes. Evidence for mitochondrial adaptation and the emergence of reproductive isolation comes from livebearing fishes (Poeciliidae) that have colonized hydrogen sulfide (H2S) rich environments (Tobler et al. 2018). H2S is a potent respiratory toxicant that binds to cytochrome c oxidase (COX) in OxPhos and is detoxified through the mitochondrial sulfide: quinone oxidoreductase pathway (Tobler et al. 2016). Sulfide spring fishes have adapted to the toxic environment by modifying both toxicity targets associated with OxPhos and mitochondrial detoxification pathways (Kelley et al. 2016; Brown et al. 2018), leading to a reduced susceptibility of COX (Pfenninger et al. 2014), an increased ability for H2S detoxification (unpublished data), and ultimately a maintenance of mitochondrial (unpublished data) and organismal function (Tobler et al. 2011) in the presence of H2S. The evolution of increased sulfide tolerance has been linked to reproductive isolation and a reduction of gene flow between multiple population pairs that inhabit adjacent sulfidic and non-sulfidic habitats, despite small spatial scales (in some instances <100 m) and a lack of physical barriers that prevent fish migration (Plath et al. 2013).

In the absence of habitat preferences and selection against immigrants, mitochondrial adaptation may impact prezygotic reproductive isolation through sexual selection. Theoretically, traits under divergent selection can simultaneously serve as stimuli during mate choice and cause non-random mating, with concomitant consequences for gene flow (Servedio et al. 2011). Even though some molecular phenotypes can serve as direct cues during mate choice (e.g., polymorphisms at major histocompatibility complex loci; Eizaguirre et al. 2009), we do not know of a mechanism by which potential mating partners can directly sense each other’s mitochondrial function. However, it has been hypothesized that mitochondrial function impacts the expression of condition-dependent sexually selected traits (Hill and Johnson 2013; Hill 2018). If the expression of sexually selected traits critical for mate choice is an indicator of efficient cellular respiration under particular environmental conditions (i.e., if they serve as an indicator of mate quality), non-random mating may result during mitochondrial adaptation even in the absence of reduced survival in a mismatched habitat (van Doorn et al. 2009). Although there is some evidence that mitochondrial function can affect the expression of sexually selected traits (Cantarero and Alonso-Alvarez 2017), there are currently no empirical examples that mitochondrial adaptation can lead to speciation through sexual selection.

Finally, prezygotic isolation may occur post-mating if mitochondrial adaptation impacts sperm competition. A consequence of the maternal inheritance of mitochondria is that deleterious mutations in mitochondrial genomes that only affect males may spread in populations if the effects are neutral or beneficial for females (so called “mother’s curse” mutations; Gemmell et al. 2004). Indeed, mitochondrial function has been linked to sperm production and performance (Nakada et al. 2006; Amaral et al. 2013; Vaught and Dowling 2018). So, it is conceivable that selection on mitochondrial function that mediates local adaptation (i.e., viability) of individuals to particular environmental conditions could have inadvertent pleiotropic consequences for impaired sperm performance. Sperm competition mediated by mitochondrial function has previously been hypothesized to play a role in speciation, although this has mostly been examined in the context of postzygotic reproductive isolation (Dowling et al. 2008; Gershoni et al. 2009; Clark et al. 2010; Ålund et al. 2013).

Critical gaps in our knowledge

Both theoretical and empirical evidence suggest that mitochondria play a key role in speciation, potentially mediating reproductive isolation in a variety of ways. Some authors have even suggested that mito-nuclear dynamics may be a key driver of diversification in metazoans (Gershoni et al. 2009; Hill 2016, 2017). However, there are three reasons for taking a cautionary look at this perspective: (1) Rapid species diversification has occurred in the absence of significant mitochondrial differentiation in many animal groups. Prime examples include adaptive radiations of cichlids in the Great Lakes of Africa, where in some instances hundreds of species with essentially identical mitochondrial genomes arose (e.g., Nevado et al. 2011; Salzburger 2018). (2) Mitochondrial capture, the replacement of the mitochondrial genome of one species with that of another, appears to be common during vertebrate diversification. This is particularly evident in discordant patterns of phylogenetic hypotheses inferred from mitochondrial and nuclear DNA (Funk and Omland 2003; Toews and Brelsford 2012). If mito-nuclear interactions were strong and a primary mediator of reproductive isolation, mitochondrial capture should be rare, unless corresponding nuclear genes were also introgressed (Sloan et al. 2017; Morales et al. 2018). (3) Despite compelling circumstantial evidence, there is still much ground to cover to conclude that mitochondrially-mediated reproductive isolation was key to the origin of new species. In the following sections, we highlight critical gaps in our knowledge of mitochondria’s role in the speciation process.

Mitochondrially-mediated reproductive isolation: a cause or a consequence of speciation?

Even though mitochondria can potentially play a role in mediating various mechanisms of reproductive isolation, most empirical evidence available to date suggests a role for intrinsic mito-nuclear incompatibilities (e.g., Nagao et al. 1998; Sackton et al. 2003; Ellison et al. 2008; Ross et al. 2011; Gagnaire et al. 2012; Meiklejohn et al. 2013; Lee-Yaw et al. 2014; Trier et al. 2014; Bar-Yaacov et al. 2015; Chang et al. 2016; Ma et al. 2016; Morales et al. 2018). In many cases, evidence for intrinsic incompatibilities comes from comparisons of species pairs that are quite divergent and completed the speciation process a long time ago (Rand et al. 2006; Ellison et al. 2008; Shipley et al. 2016; Prokić et al. 2018). For the most part, the evolutionary forces and temporal dynamics driving divergence in genes associated with mitochondrial function—and ultimately the origin of reproductive isolation—remain unknown. This gap of knowledge directly pertains to a major open question in speciation biology: in what order do different mechanisms of reproductive isolation arise during the speciation process (Marie Curie Speciation Network 2012)?

If mitochondria indeed play a key role in animal speciation, we predict that mechanisms of reproductive isolation directly related to mitochondrial function arise early in the speciation process. This can conceivably happen, especially if selection drives divergence in mitochondrial function, and if divergence in mitochondrial function in turn impacts gene flow either through pre- or postzygotic isolation (as described above). However, mito-nuclear hybrid incompatibilities—the mechanisms of reproductive isolation for which we have most empirical evidence—might be a mere indicator that speciation has actually occurred, accumulating after some degree of reproductive isolation has evolved through other mechanisms. In this case, mitochondrial genes with higher mutation rates might diverge through neutral processes in (reproductive) isolation, with compensatory nuclear mutations accruing over time and ultimately leading to observable mito-nuclear incompatibilities (analogous to the allopatric speciation model). This scenario has to be considered particularly in study systems where intrinsic incompatibilities were documented between divergent species that do not typically exhibit appreciable levels of gene flow. If mitochondrially-mediated intrinsic incompatibilities appear during late stages of or after speciation, mito-nuclear incompatibilities may have little to do with driving the process of speciation (i.e., explanations of how and why new species arise), even though they may contribute to the maintenance of species boundaries and be useful in delineating species (Hill 2017). To assess the role of mitochondria during the speciation process in the future, we need to particularly investigate mito-nuclear dynamics in study systems with ongoing speciation to understand the ultimate mechanisms driving divergence in mitochondrial function and how the timing of this divergence compares to the emergence of other mechanisms of reproductive isolation.

Mito-nuclear incompatibilities and genome-wide gene flow

The growing number of natural study systems with on-going speciation is testament to the power of ecologically-mediated natural selection in initiating speciation processes. However, there is also evidence that speciation processes—once initiated—may not necessarily be completed, and progress along the speciation continuum may even be reversed (Nosil et al. 2009). In the context of mitochondria, an open question is whether divergence of mitochondrial function and the emergence of mitochondrially-mediated reproductive isolation is sufficient to cause speciation. Indeed, some well-documented cases of mito-nuclear incompatibilities that have emerged along environmental gradients occur in absence of strong differentiation in nuclear genomes; i.e., there are mechanisms that prevent admixture of genes associated with mitochondrial function, but not other genes. For example, the eastern yellow robin (Eopsaltria australis) exhibits divergence in genes associated with mitochondrial function along a climatic gradient in Australia, while nuclear gene flow among the same populations is ongoing across much of the genome (Pavlova et al. 2013; Lamb et al. 2018; Morales et al. 2018). Similarly, populations of the mummichog (F. heteroclitus) exhibit a well-characterized gradient in mitochondrial genotypes along a latitudinal gradient, with significant mito-nuclear interactions in hybrids where divergent mitochondrial lineages come into secondary contact (Haney et al. 2009; McKenzie et al. 2015, 2017). Still, genome-wide genetic divergence is restricted to a relatively small number of loci that are presumably involved in epistatic interactions with mitochondrial loci (Baris et al. 2017). Intriguingly, nuclear loci presumably involved in mito-nuclear interactions were not close to any known genes encoding proteins associated with OxPhos functionality (Baris et al. 2017), highlighting that the genetic basis and regulatory mechanisms that modulate mitochondrial function are still not completely resolved.

Localized divergence in the genome is not unprecedented in the context of ecological speciation. If divergent selection is driving population divergence—and accordingly early stages of speciation—genetic divergence is expected to occur primarily at loci relevant for fitness along the selection gradient, while other regions of the genome are homogenized by recombination and gene flow (creating so called genomic islands of divergence; Nosil and Feder 2012). Proximity of selected loci on chromosomes, recombination rates, and the strength of divergent selection are expected to determine the size of genomic islands, and divergence hitchhiking may cause genomic islands to grow beyond selected loci even if gene flow is present (Via and West 2008). Whether divergence in genes associated with mitochondrial function fit this model remains to be tested. The striking differentiation of mitochondrial genomes (and corresponding nuclear loci) documented in Eopsaltria and Fundulus may represent genomic islands representative of early stages of speciation. The question is whether mito-nuclear incompatibilities in these cases are strong enough to overcome the homogenizing effect of gene flow and result in complete reproductive isolation.

The role of mito-nuclear interactions when multiple mechanisms of reproductive isolation coincide

Explaining reproductive isolation can be satisfyingly simple, for example when intrinsic incompatibilities with a simple genetic basis lead to hybrid inviability or sterility (Naisbit et al. 2002; Wright et al. 2013). In many cases, however, intrinsic incompatibilities are not a qualitative trait, but they lead to quantitative changes in hybrid performance (Moyle and Graham 2005; Good et al. 2008). More importantly, incompatibilities may be context-dependent (see above), and multiple mechanisms of reproductive isolation are likely to co-occur in any given system (Ramsey et al. 2003; Nosil 2012), both because they can arise independently and because the emergence of one reproductive barrier can lead to another (e.g., through reinforcement; Servedio and Noor 2003). Consequently, it is critical that we understand mitochondrially-mediated reproductive isolation in the context of other possible mechanisms.

Even if there is direct or indirect evidence for mito-nuclear incompatibilities, this does not necessarily mean that such incompatibilities explain much variation in the initial build-up or the maintenance of reproductive isolation. If reproductive isolation arises in ways unrelated to mitochondrial function, mutations in the mitochondrial genomes and compensatory nuclear mutations may simply arise as a byproduct (i.e., as an indicator speciation is happening, as discussed above), playing a minor role as a barrier maintaining divergence across populations. Still, mito-nuclear interactions arising as a byproduct of other isolating mechanisms could drive speciation to completion. Conversely, mito-nuclear incompatibilities (intrinsic or extrinsic) may arise early in the speciation process. In this case, we would expect strong selection on prezygotic mechanisms of reproductive isolation that prevent the formation of hybrids with low fitness (i.e., reinforcement; Servedio and Noor 2003). So, a major remaining frontier in our understanding of speciation—inside and outside of the context of mitochondria—is to understand how multiple mechanisms of reproductive isolation arise sequentially, how they interact, and how they each contribute to total reproductive isolation observed in any given system. Disentangling the relative contribution of different mechanisms of reproductive isolation in multiple systems is an “essential, but unfortunately not glamorous” (Marie Curie Speciation Network 2012) task requisite for understanding the general role of mitochondria in the speciation process, especially if we want to consider them to be a cornerstone—rather than just a possibility—in animal diversification (Gershoni et al. 2009; Hill 2016, 2017).

Future directions

Unifying genetic and ecological perspectives of speciation through the lens of mitochondria will require connecting specific sources of selection to divergence in mitochondrial function in lineages inhabiting different environments, explaining how differences in mitochondrial function mediate adaptation, and how they relate to different mechanisms of reproductive isolation. Excitingly, hypotheses about the role of mitochondria in speciation can be addressed at and traced across levels of organization by using genetic, biochemical, and physiological approaches. A key challenge is to elucidate when in the speciation process mitochondrially-mediated mechanisms of reproductive isolation actually arise. Even though speciation can occur rapidly, it is not feasible to follow the emergence of different isolating mechanisms sequentially in natural populations. We see two possible approaches to address this problem: (1) Experimental evolution studies could exert artificial selection on mitochondrial function and directly test whether and how reproductive isolation arises when mitochondria evolve. Such studies are naturally limited to model systems with short generation times. Fruit flies of the genus Drosophila and nematodes of the genus Caenorhabditis may be particularly suitable in this endeavor, because mito-nuclear interactions have been invoked in studies of natural populations (Hoekstra et al. 2013; Chang et al. 2016; Mossman et al. 2016; Haddad et al. 2018). (2) Comparative approaches can leverage cases of parallel speciation in response to similar sources of selection but with variable progress along the speciation continuum, testing how mitochondrially-mediated reproductive isolation accumulates across lineages with variable progress along the speciation continuum.

In the pursuit of these questions, we are leveraging a natural study system with clearly defined sources of selection that directly impact mitochondrial function and with evolutionary replication across broad spatial and phylogenetic scales. Multiple genera of livebearing fishes in the family Poeciliidae have colonized freshwater springs rich in hydrogen sulfide (H2S) across the Americas (Tobler et al. 2018). H2S exerts selection on mitochondria in multiple ways, as it inhibits OxPhos function and is also detoxified through enzymes bound to the inner mitochondrial membrane (Tobler et al. 2016), allowing for the establishment of direct links between an ecological source of selection and adaptive modifications of mitochondrial function (evidenced by selection on and differential expression of OxPhos and mitochondrial detoxificantion genes: Pfenninger et al. 2014; Kelley et al. 2016; Passow et al. 2017; Brown et al. 2018, Forthcoming 2019). At the same time, populations adapting to H2S-rich environments exhibit significant population genetic differentiation from ancestral populations in non-sulfidic habitats despite small spatial scales, and progress along the speciation continuum is variable across evolutionarily-independent lineages (Palacios et al. 2013; Plath et al. 2013; Riesch et al. 2016). While there is strong evidence for prezygotic reproductive isolation mediated by natural and sexual selection against immigrants (Tobler et al. 2009; Plath et al. 2010, 2013), the role of mitochondrial adaptation in mediating reproductive isolation—especially through postzygotic mechanisms—remains to be established conclusively. Nonetheless, sulfide spring poeciliids are a prime study system to address outstanding questions about the role of mitochondria in animal diversification.

Considering that a variety of ecological sources of selection have been implicated in driving mitochondrial adaptation (Hill et al. 2018), progress toward elucidating the role of mitochondria in animal diversification will be greatly facilitated by identifying other study systems where selection on mitochondrial function coincides with replicated and ongoing speciation with gene flow. Focusing on such systems will help to complement our already solid understanding of genetic perspectives of mitochondrially-mediated speciation with ecological perspectives that focus on how speciation processes unfold. In addition, broadening our perspectives of mitochondrial function beyond the powerhouse (i.e., the aerobic production of ATP associated with OxPhos) might reveal intriguing new mechanisms about how mitochondrial and nuclear genomes interact, especially because there are epistatic effects between mitochondrial genes and nuclear loci that we do not currently understand (Rand 2017). Such efforts will ultimately allow us to back theoretical predictions about mitochondria’s role in speciation with solid empirical evidence.

Acknowledgments

We thank J. Havird and G. Hill for organizing the “Beyond the Powerhouse: Integrating Mitonuclear Evolution, Physiology, and Theory in Comparative Biology” symposium at the 2019 SICB Meeting, as well as all participants for sharing their perspectives on the topic. Travel and support funds to attend the 2019 meeting of the Society for Integrative and Comparative Biology came from the Alvin and RosaLee Sarachek Fellowship (Kansas State University), the National Science Foundation (IOS-1839203), the Company of Biologists (EA1694), The Crustacean Society, and the Divisions of Comparative Physiology and Biochemistry, Invertebrate Zoology, and Phylogenetics and Comparative Biology.

Funding

This work was supported by the National Science Foundation [IOS-1557860] and the US Army Research Office [W911NF-15-1-0175, W911NF-16-1-0225].

References

Adrion

JR

2016

.

The roles of compensatory evolution and constraint in aminoacyl tRNA synthetase evolution

.

Mol Biol Evol

33

:

152

–

61

.

Ålund

M

2013

.

Low fertility of wild hybrid male flycatchers despite recent divergence

.

Biol Lett

9

:

20130169.

Amaral

A

2013

.

Mitochondria functionality and sperm quality

.

Reproduction

146

:

R163

–

74

.

Anderson

JB

2010

.

Determinants of divergent adaptation and Dobzhansky–Muller interaction in experimental yeast populations

.

Curr Biol

20

:

1383

–

8

.

Ballard

JWO

1995

.

Is mitochondrial DNA a strictly neutral marker?

Trends Ecol Evol

10

:

485

–

8

.

Bar-Yaacov

D

2015

.

Mitochondrial involvement in vertebrate speciation? The case of mito-nuclear genetic divergence in chameleons

.

Genome Biol Evol

7

:

3322

–

36

.

Baris

TZ

2017

.

Evolved genetic and phenotypic differences due to mitochondrial–nuclear interactions

.

PLoS Genet

13

:

e1006517.

Barreto

FS

2013

.

Elevated oxidative damage is correlated with reduced fitness in interpopulation hybrids of a marine copepod

.

Proc R Soc B

280

:

20131521.

Barrett

RDH

2011

.

Molecular spandrels: tests of adaptation at the genetic level

.

Nat Rev Genet

12

:

767

–

80

.

Bazin

E

2006

.

Population size does not influence mitochondrial genetic diversity in animals

.

Science

312

:

570

–

2

.

Blier

PU

2001

.

Natural selection and the evolution of mtDNA-encoded peptides: evidence for intergenomic co-adaptation

.

Trends Genet

17

:

400

–

6

.

Brown

AP

2018

.

Concordant changes in gene expression and nucleotides underlie independent adaptation to hydrogen-sulfide-rich environments

.

Genome Biol Evol

10

:

2867

–

81

.

Brown

AP

2019

. Local ancestry analysis reveals genomic convergence in extremophile fishes. Philos Trans R Soc B. (doi: 10.1098/rstb.2018.0240).

Bryant

HJ

2018

. Subspecies differences in thermal acclimation of mitochondrial function and the role of uncoupling proteins in killifish. J Exp Biol published online (doi: 10.1242/jeb.186320).

Burton

RS

2006

.

The sorry state of F2 hybrids: consequences of rapid mitochondrial DNA evolution in allopatric populations

.

Am Nat

168

:

S14

–

24

.

Burton

RS

2013

.

Cytonuclear genomic interactions and hybrid breakdown

.

Annu Rev Ecol Evol Syst

44

:

281

–

302

.

Butlin

RK

2008

.

Sympatric, parapatric or allopatric: the most important way to classify speciation?

.

Philos Trans R Soc B Biol Sci

363

:

2997

–

3007

.

Byers

K

2017

.

Molecular mechanisms of adaptation and speciation: why do we need an integrative approach?

Mol Ecol

26

:

277

–

90

.

Camus

MF

2017

.

Experimental support that natural selection has shaped the latitudinal distribution of mitochondrial haplotypes in Australian Drosophila melanogaster

.

Mol Biol Evol

34

:

2600

–

12

.

Cantarero

A

2017

.

Mitochondria-targeted molecules determine the redness of the zebra finch bill

.

Biol Lett

13

:

20170455.

Chang

C-C

2016

.

Mitochondrial–nuclear epistasis impacts fitness and mitochondrial physiology of interpopulation Caenorhabditis briggsae hybrids

.

G3 (Bethesda)

6

:

209

–

19

.

Chung

DJ

2015

.

Mechanisms and costs of mitochondrial thermal acclimation in a eurythermal killifish (Fundulus heteroclitus)

.

J Exp Biol

218

:

1621

–

31

.

Clark

ME

2010

.

Behavioral and spermatogenic hybrid male breakdown in Nasonia

.

Heredity

104

:

289

–

301

.

D’Souza

AR

2018

.

Mitochondrial transcription and translation: overview

.

Essays Biochem

62

:

309

–

20

.

Dahlhoff

E

1991

.

Temperature effects on mitochondria from hydrothermal vent invertebrates: evidence for adaptation to elevated and variable habitat temperatures

.

Physiol Zool

64

:

1490

–

508

.

Darwin

C.

1859

.

On the origin of species based on natural selection, or the preservation of favoured races in the struggle of life

.

London (UK

):

John Murray

.

Dobzhansky

T.

1937

.

Genetics and the origin of species

.

New York (NY

):

Columbia University Press

.

Dowling

DK

2008

.

Evolutionary implications of non-neutral mitochondrial genetic variation

.

Trends Ecol Evol

23

:

546

–

54

.

Eizaguirre

C

2009

.

Speciation accelerated and stabilized by pleiotropic major histocompatibility complex immunogenes

.

Ecol Lett

12

:

5

–

12

.

Ellison

CK

2008

.

Hybrid breakdown and mitochondrial dysfunction in hybrids of Nasonia parasitoid wasps

.

J Evol Biol

21

:

1844

–

51

.

Friedman

JR

2014

.

Mitochondrial form and function

.

Nature

505

:

335

–

43

.

Funk

DJ

2003

.

Species-level paraphyly and polyphyly: frequency, causes, and consequences, with insights from animal mitochondrial DNA

.

Annu Rev Ecol Evol Syst

34

:

397

–

423

.

Gagnaire

PA

2012

.

Comparative genomics reveals adaptive protein evolution and a possible cytonuclear incompatibility between European and American Eels

.

Mol Biol Evol

29

:

2909

–

19

.

Galluzzi

L

2012

.

Mitochondria: master regulators of danger signalling

.

Nat Rev Mol Cell Biol

13

:

780

–

8

.

Gavrilets

S.

2004

.

Fitness landscapes and the origin of species

.

Princeton (NJ

):

Princeton University Press

.

Gebiola

M

2016

.

“Darwin’s corollary” and cytoplasmic incompatibility induced by Cardinium may contribute to speciation in Encarsia wasps (Hymenoptera: Aphelinidae)

.

Evolution

70

:

2447

–

58

.

Gemmell

NJ

2004

.

Mother’s curse: the effect of mtDNA on individual fitness and population viability

.

Trends Ecol Evol

19

:

238

–

44

.

Gershoni

M

2009

.

Mitochondrial bioenergetics as a major motive force of speciation

.

Bioessays

31

:

642

–

50

.

Gibson

JD

2013

.

Genetic and developmental basis of F2 hybrid breakdown in Nasonia parasitoid wasps

.

Evolution

67

:

2124

–

32

.

Good

JM

2008

.

Asymmetry and polymorphism of hybrid male sterility during the early stages of speciation in house mice

.

Evolution

62

:

50

–

65

.

Greenberg

A

2003

.

Ecological adaptation during incipient speciation revealed by precise gene replacement

.

Science

302

:

1754

–

7

.

Gu

MB

2012

.

Differences in mtDNA whole sequence between Tibetan and Han populations suggesting adaptive selection to high altitude

.

Gene

496

:

37

–

44

.

Haddad

R

2018

.

The genetic architecture of intra-species hybrid mito-nuclear epistasis

.

Front Genet

9

:

481.

Haney

RA

2009

.

The comparative phylogeography of east coast estuarine fishes in formerly glaciated sites: persistence versus recolonization in Cyprinodon variegatus ovinus and Fundulus heteroclitus macrolepidotus

.

J Hered

100

:

284

–

96

.

Havird

JC

2016

.

The roles of mutation, selection, and expression in determining relative rates of evolution in mitochondrial versus nuclear genomes

.

Mol Biol Evol

33

:

3042

–

53

.

Havird

JC

2015

.

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

.

Evolution

69

:

3069

–

81

.

Healy

TM

2017

.

Mitochondrial genotype and phenotypic plasticity of gene expression in response to cold acclimation in killifish

.

Mol Ecol

26

:

814

–

30

.

Hill

GE.

2016

.

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

.

Ecol Evol

6

:

5831

–

42

.

Hill

GE.

2017

.

The mitonuclear compatibility species concept

.

Auk

134

:

393

–

409

.

Hill

GE.

2018

.

Mitonuclear mate choice: a missing component of sexual selection theory?

BioEssays

40

:

1700191.

Hill

GE

2018

. Assessing the fitness consequences of mitonuclear interactions in natural populations. Biol Rev Camb Philos Soc published online (doi:10.1111/brv.12493).

Hill

GE

2013

.

The mitonuclear compatibility hypothesis of sexual selection

.

Proc R Soc B

280

:

20131314.

Hoekstra

LA

2018

.

Energy demand and the context‐dependent effects of genetic interactions underlying metabolism

.

Evol Lett

2

:

102

–

13

.

Hoekstra

LA

2013

.

Pleiotropic effects of a mitochondrial–nuclear incompatibility depend upon the accelerating effect of temperature in Drosophila

.

Genetics

195

:

1129

–

39

.

James

JE

2016

.

The rate of adaptive evolution in animal mitochondria

.

Mol Ecol

25

:

67

–

78

.

Johannesson

K.

2001

.

Parallel speciation: a key to sympatric divergence

.

Trends Ecol Evol

16

:

148

–

53

.

Kelley

JL

2016

.

Mechanisms underlying adaptation to life in hydrogen sulfide rich environments

.

Mol Biol Evol

33

:

1419

–

34

.

Kulmuni

J

2017

.

Intrinsic incompatibilities evolving as a by-product of divergent ecological selection: considering them in empirical studies on divergence with gene flow

.

Mol Ecol

26

:

3093

–

103

.

Lamb

AM

2018

.

Climate-driven mitochondrial selection: a test in Australian songbirds

.

Mol Ecol

27

:

898

–

918

.

Langerhans

RB

2007

.

Ecological speciation in Gambusia fishes

.

Evolution

61

:

2056

–

74

.

Lasne

C

2019

.

Quantifying the relative contributions of the X chromosome, autosomes, and mitochondrial genome to local adaptation

.

Evolution

73

:

262

–

77

.

Lee-Yaw

JA

2014

.

Individual performance in relation to cytonuclear discordance in a northern contact zone between long‐toed salamander (Ambystoma macrodactylum) lineages

.

Mol Ecol

23

:

4590

–

602

.

Levin

L

2014

.

Mito-nuclear co-evolution: the positive and negative sides of functional ancient mutations

.

Front Genet

5

:

448.

Li

X-D

2018

.

Positive selection drove the adaptation of mitochondrial gene to the demands of flight and high-altitude environments in grasshoppers

.

Front Genet

9

:

605.

Luo

S

2018

.

Biparental inheritance of mitochondrial DNA in humans

.

Proc Natl Acad Sci U S A

115

:

13039

–

44

.

Lynch

M

1998

.

Deleterious mutation accumulation in organelle genomes

.

Genetica

102–103

:

29

–

39

.

Ma

H

2016

.

Incompatibility between nuclear and mitochondrial genomes contributes to an interspecies reproductive barrier

.

Cell Metab

24

:

283

–

94

.

Maheshwari

S

2011

.

The genetics of hydrid incompatibilities

.

Annu Rev Genet

45

:

331

–

55

.

Marie Curie Speciation Network

.

2012

.

What do we need to know about speciation?

Trends Ecol Evol

27

:

27

–

39

.

Mayr

E.

1963

.

Animal species and evolution

.

Cambridge (MS

):

Harvard University Press

.

McFarlane

SE

2016

.

Hybrid dysfunction expressed as elevated metabolic rate in male Ficedula flycatchers

.

PLoS ONE

11

:

e0161547.

McKenzie

DJ

2015

.

Evidence for a bimodal distribution of hybrid indices in a hybrid zone with high admixture

.

R Soc Open Sci

2

:

150285.

McKenzie

DL

2017

.

Intrinsic reproductive isolating mechanisms in the maintenance of a hybrid zone between ecologically divergent subspecies

.

J Evol Biol

30

:

848

–

64

.

McKenzie

JL

2016

.

Steep, coincident, and concordant clines in mitochondrial and nuclear‐encoded genes in a hybrid zone between subspecies of Atlantic killifish, Fundulus heteroclitus

.

Ecol Evol

6

:

5771

–

87

.

McKinnon

J

2004

.

Evidence for ecology’s role in speciation

.

Nature

429

:

294

–

8

.

Meiklejohn

CD

2013

.

An incompatibility between a mitochondrial tRNA and its nuclear‐encoded tRNA synthetase compromises development and fitness in Drosophila

.

PLoS Genet

9

:

e1003238.

Meiklejohn

CD

2007

.

Positive and negative selection on the mitochondrial genome

.

Trends Genet

23

:

259

–

63

.

Montooth

KL

2010

.

Mitochondrial–nuclear epistasis affects fitness within species but does not contribute to fixed incompatibilities between species of Drosophila

.

Evolution

64

:

3364

–

79

.

Morales

HE

2018

.

Concordant divergence of mitogenomes and a mitonuclear gene cluster in bird lineages inhabiting different climates

.

Nat Ecol Evol

2

:

1258

–

67

.

Mossman

JA

2016

.

Mitonuclear epistasis for development time and its modification by diet in Drosophila

.

Genetics

203

:

463

–

84

.

Moyle

LC

2005

.

Genetics of hybrid incompatibility between Lycopersicon esculentum and L. hirsutum

.

Genetics

169

:

355

–

73

.

Muller

HJ.

1942

.

Isolating mechanisms, evolution and temperature

.

Biol Symp

6

:

71

–

125

.

Nagao

Y

1998

.

Decreased physical performance of congenic mice with mismatch between the nuclear and the mitochondrial genome

.

Genes Genet Syst

73

:

21

–

7

.

Naisbit

RE

2002

.

Hybrid sterility, Haldane’s rule and speciation in Heliconius cydno and H. melpomene

.

Genetics

161

:

1517

–

26

.

Nakada

K

2006

.

Mitochondria-related male infertility

.

Proc Natl Acad Sci U S A

103

:

15148

–

53

.

Neiman

M

2009

.

The causes of mutation accumulation in mitochondrial genomes

.

Proc R Soc B

276

:

1201

–

9

.

Nevado

B

2011

.

Repeated unidirectional introgression of nuclear and mitochondrial DNA between four congeneric Tanganyikan cichlids

.

Mol Biol Evol

28

:

2253

–

67

.

Nosek

J

1998

.

Linear mitochondrial genomes: 30 years down the line

.

Trends Genet

14

:

184

–

8

.

Nosil

P.

2012

.

Ecological speciation

.

Oxford

:

Oxford University Press

. p.

280

.

Nosil

P

2008

.

Heterogeneous genomic differentiation between walking-stick ecotypes: “Isolation by adaptation” and multiple roles for divergent selection

.

Evolution

62

:

316

–

36

.

Nosil

P

2012

.

Genomic divergence during speciation: causes and consequences

.

Trans R Soc B

367

:

332

–

42

.

Nosil

P

2009

.

Ecological explanations for (incomplete) speciation

.

Trends Ecol Evol

24

:

145

–

56

.

Nosil

P

2005

.

Perspective: reproductive isolation caused by natural selection against immigrants from divergent habitats

.

Evolution

59

:

705

–

19

.

Nunnari

J

2012

.

Mitochondria: in sickness and in health

.

Cell

148

:

1145

–

59

.

Orr

HA.

2005

.

The genetic basis of reproductive isolation: insights from Drosophila

.

Proc Natl Acad Sci U S A

102

:

6522

–

6

.

Orr

HA

2000

.

Speciation by postzygotic isolation: forces, genes and molecules

.

Bioessays

22

:

1085

–

94

.

Osada

N

2012

.

Mitochondrial–nuclear interactions and accelerated compensatory evolution: evidence from the primate cytochrome c oxidase complex

.

Mol Biol Evol

29

:

337

–

46

.

Palacios

M

2013

.

The rediscovery of a long described species reveals additional complexity in speciation patterns of poeciliid fishes in sulfide springs

.

PLoS ONE

8

:

e71069.

Passow

CN

2017

.

The roles of plasticity and evolutionary change in shaping gene expression variation in natural populations of extremophile fish

.

Mol Ecol

26

:

6384

–

99

.

Pavlova

A

2013

.

Perched at the mito-nuclear crossroads: divergent mitochondrial lineages correlate with environment in the face of ongoing nuclear gene flow in an Australian bird

.

Evolution

67

:

3412

–

28

.

Pfenninger

M

2014

.

Parallel evolution of cox genes in H2S-tolerant fish as key adaptation to a toxic environment

.

Nat Commun

5

:

3873

.

Plath

M

2013

.

Genetic differentiation and selection against migrants in evolutionarily replicated extreme environments

.

Evolution

67

:

2647

–

61

.

Plath

M

2010

.

Complementary effects of natural and sexual selection against immigrants maintains differentiation between locally adapted fish

.

Naturwissenschaften

97

:

769

–

74

.

Presgraves

DC.

2010

.

The molecular evolutionary basis of species formation

.

Nat Rev Genet

11

:

175

–

80

.

Presgraves

DC

2003

.

Adaptive evolution drives divergence of a hybrid inviability gene between two species of Drosophila

.

Nature

423

:

715

–

9

.

Prokić

MD

2018

.

Oxidative cost of interspecific hybridization: a case study of two Triturus species and their hybrids

.

J Exp Biol

221

:pii: jeb182055.

Quirós

PM

2016

.

Mitonuclear communication in homeostasis and stress

.

Nat Rev Mol Cell Biol

17

:

213

–

26

.

Qvarnström

A

2016

.

Climate adaptation and speciation: particular focus on reproductive barriers in Ficedula flycatchers

.

Evol Appl

9

:

119

–

34

.

Ramsey

J

2003

.

Components of reproductive isolation between the monkeyflowers Mimulus lewisii and M. cardinalis (Phrymaceae)

.

Evolution

57

:

1520

–

34

.

Rand

DM.

2001

.

The units of selection on mitochondrial DNA

.

Annu Rev Ecol Syst

32

:

415

–

48

.

Rand

DM.

2017

.

Fishing for adaptive epistasis using mitonuclear interactions

.

PLoS Genet

13

:

e1006662.

Rand

DM

2006

.

Nuclear–mitochondrial epistasis and Drosophila aging: introgression of Drosophila simulans mtDNA modifies longevity in D. melanogaster nuclear backgrounds

.

Genetics

172

:

329

–

41

.

Rand

DM

2004

.

Cytonuclear coevolution: the genomics of cooperation

.

Trends Ecol Evol

19

:

645

–

53

.

Riesch

R

2016

.

Extremophile Poeciliidae: multivariate insights into the complexity of speciation along replicated ecological gradients

.

BMC Evol Biol

16

:

136

.

Ross

J

2011

.

Caenorhabditis briggsae recombinant inbred line genotypes reveal inter-strain incompatibility and the evolution of recombination

.

PLoS Genet

7

:

e1002174.

Rundle

HD

2000

.

Natural selection and parallel speciation in sympatric sticklebacks

.

Science

287

:

306

–

8

.

Rundle

HD

2005

.

Ecological speciation

.

Ecol Lett

8

:

336

–

52

.

Sackton

TB

2003

.

Cytonuclear coadaptation in Drosophila: disruption of cytochrome c oxidase activity in backcross genotypes

.

Evolution

57

:

2315

–

25

.

Salzburger

W.

2018

.

Understanding explosive diversification through cichlid fish genomics

.

Nat Rev Genet

19

:

705

–

17

.

Schluter

D.

2000

.

The ecology of adaptive radiation

.

Oxford

:

Oxford University Press

.

Schluter

D.

2001

.

Ecology and the origin of species

.

Trends Ecol Evol

16

:

372

–

80

.

Schluter

D.

2009

.

Evidence for ecological speciation and its alternative

.

Science

323

:

737

–

41

.

Scott

GR

2011

.

Molecular evolution of cytochrome c oxidase underlies high-altitude adaptation in the bar-headed goose

.

Mol Biol Evol

28

:

351

–

63

.

Servedio

MR

2003

.

The role of reinforcement in speciation: theory and data

.

Annu Rev Ecol Evol Syst

34

:

339

–

64

.

Servedio

MR

2011

.

Magic traits in speciation: ‘magic’ but not rare?

.

Trends Ecol Evol

26

:

389

–

97

.

Shen

Y-Y

2010

.

Adaptive evolution of energy metabolism genes and the origin of flight in bats

.

Proc Natl Acad Sci U S A

107

:

8666

–

71

.

Shipley

JR

2016

.

Asymmetric energetic costs in reciprocal-cross hybrids between carnivorous mice (Onychomys)

.

J Exp Biol

219

:

3803

–

9

.

Silva

GJJ

2014

.

Thermal adaptation and clinal mitochondrial DNA variation of European anchovy

.

Proc R Soc B

281

:

20141093.

Sloan

DB

2017

.

The on-again, off-again relationship between mitochondrial genomes and species boundaries

.

Mol Ecol

26

:

2212

–

36

.

Sokolova

I.

2018

.

Mitochondrial adaptations to variable environments and their role in animals’ stress tolerance

.

Integr Comp Biol

58

:

519

–

31

.

Taanman

J-W.

1999

.

The mitochondrial genome: structure, transcription, translation and replication

.

Biochim Biophys Acta

1410

:

103

–

23

.

Templeton

AR.

1980

.

The theory of speciation via the founder principle

.

Genetics

94

:

1011

–

38

.

Tobler

M

2018

.

Extreme environments and the origins of biodiversity: adaptation and speciation in sulfide springs

.

Mol Ecol

27

:

843

–

59

.

Tobler

M

2011

.

Evolution in extreme environments: replicated phenotypic differentiation in livebearing fish inhabiting sulfidic springs

.

Evolution

65

:

2213

–

28

.

Tobler

M

2016

.

The evolutionary ecology of animals inhabiting hydrogen sulfide-rich environments

.

Annu Rev Ecol Evol Syst

47

:

239

–

62

.

Tobler

M

2009

.

Natural and sexual selection against immigrants maintains differentiation among micro-allopatric populations

.

J Evol Biol

22

:

2298

–

304

.

Toews

DPL

2012

.

The biogeography of mitochondrial and nuclear discordance in animals

.

Mol Ecol

21

:

3907

–

30

.

Trier

CN

2014

.

Evidence for mito-nuclear and sex-linked reproductive barriers between the hybrid Italian sparrow and its parent species

.

PLoS Genet

10

:

e1004075.

Vakifahmetoglu-Norberg

H

2017

.

The role of mitochondria in metabolism and cell death

.

Biochem Biophys Res Commun

482

:

426

–

31

.

van der Sluis

EO

2015

.

Parallel structural evolution of mitochondrial ribosomes and OXPHOS complexes

.

Genome Biol Evol

9

:

1235

–

51

.

van Doorn

GS

2009

.

On the origin of species by natural selection and sexual selection

.

Science

326

:

1704

–

7

.

Vaught

RC

2018

.

Maternal inheritance of mitochondria: implications for male fertility?

Reproduction

155

:

R159

–

68

.

Via

S.

2002

.

The ecological genetics of speciation

.

Am Nat

159

:

S1

–

7

.

Via

S

2008

.

The genetic mosaic suggests a new role for hitchhiking in ecological speciation

.

Mol Ecol

17

:

4334

–

45

.

Wolf

JBW

2010

.

Speciation genetics: current status and evolving approaches

.

Philos Trans R Soc B Biol Sci

365

:

1717

–

33

.

Woodson

JD

2008

.

Coordination of gene expression between organellar and nuclear genomes

.

Nat Rev Genet

9

:

383

–

95

.

Wright

KM

2013

.

Indirect evolution of hybrid lethality due to linkage with selected locus in Mimulus guttatus

.

PLoS Biol

11

:

e1001497.

Zhang

C

2017

.

Incompatibility between mitochondrial and nuclear genomes during oogenesis results in ovarian failure and embryonic lethality

.

Dev Psychopathol

144

:

2490

–

503

.

Zhang

F

2015

.

Heterogeneous natural selection on oxidative phosphorylation genes among fishes with extreme high and low aerobic performance

.

BMC Evol Biol

15

:

173.

Zhang

Z-Y

2013

.

Functional modulation of mitochondrial cytochrome c oxidase underlies adaptation to high-altitude hypoxia in a Tibetan migratory locust

.

Proc R Soc B

280

:

20122758.

Author notes

From the symposium “Beyond the powerhouse: integrating mitonuclear evolution, physiology, and theory in comparative biology” presented at the annual meeting of the Society of Integrative and Comparative Biology, January 3–7, 2019 at Tampa, Florida.

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email:

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email:

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