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Integrative and Comparative Biology Integrative and Comparative Biology, volume 59, number 4, pp. 856–863 doi:10.1093/icb/icz132 Society for Integrative and Comparative Biology

SYMPOSIUM INTRODUCTION

Beyond the Powerhouse: Integrating Mitonuclear Evolution, Physiology, and Theory in Comparative Biology

Justin C. Havird,* Ryan J. Weaver,*,† Liliana Milani ,‡ Fabrizio Ghiselli ,‡ Ryan Greenway,§ Downloaded from https://academic.oup.com/icb/article/59/4/856/5542403 by Auburn University user on 30 April 2021 Adam J. Ramsey,¶ Ana G. Jimenez ,k Damian K. Dowling ,# Wendy R. Hood ,† Kristi L. Montooth ,** Suzanne Estes,†† Patricia M. Schulte,‡‡ Inna M. Sokolova ,§§,¶¶ and Geoffrey E. Hill 1,† *Department of Integrative Biology, University of Texas, Austin, TX 78712, USA; †Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA; ‡Department of Biological, Geological and Environmental Sciences (BiGeA), University of Bologna, Bologna, 40126, Italy; §Division of Biology, Kansas State University, Manhattan, KS 66506, USA; ¶Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA; kDepartment of Biology, Colgate University, Hamilton, NY 13346, USA; #School of Biological Sciences, Monash University, Clayton, Victoria 3800, Australia; **School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE 68502, USA; ††Department of Biology, Portland State University, Portland, OR 97201, USA; ‡‡Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; §§Department of Marine Biology, Institute of Biological Sciences, University of Rostock, Rostock, Germany; ¶¶Department of Maritime Systems, Interdisciplinary Faculty, University of Rostock, Rostock, Germany From the symposium “Beyond the powerhouse: integrating mitonuclear evolution, physiology, and theory in comparative biology” presented at the annual meeting of the Society for Integrative and Comparative Biology, January 3–7, 2019 at Tampa, Florida.

1E-mail: [email protected]

Synopsis Eukaryotes are the outcome of an ancient symbiosis and as such, eukaryotic cells fundamentally possess two genomes. As a consequence, gene products encoded by both nuclear and mitochondrial genomes must interact in an intimate and precise fashion to enable aerobic respiration in eukaryotes. This genomic architecture of eukaryotes is proposed to necessitate perpetual coevolution between the nuclear and mitochondrial genomes to maintain coadaptation, but the presence of two genomes also creates the opportunity for intracellular conflict. In the collection of papers that constitute this symposium volume, scientists working in diverse organismal systems spanning vast biological scales address emerging topics in integrative, comparative biology in light of mitonuclear interactions.

Mitonuclear evolution as integrative mitochondrial and nuclear genomes to coexist and biology cooperate, the interests of the two genomes are not The cellular mechanisms that enable aerobic res- identical and selfish conflict between them can alter piration and that sustain complex life arise from the thecourseofevolution(Gemmell et al. 2004; Wade coordinated function of the products of multiple and Drown 2016; Havird et al. 2019). The evolu- genomes—minimally both a nuclear and a mito- tionary processes that shape complex life are hy- chondrial genome (Blier et al. 2001; Rand et al. pothesized to be significantly influenced by the 2004; Bar-Yaacov et al. 2012). A single functional outcomes of selection arising from coadaptation, outcome that is the product of two independently coevolution, and genomic conflict involving mito- replicating genomes likely necessitates coadaptation chondrial and nuclear genes, but mitonuclear pro- between the gene products of the two entities (Lane cesses are only just emerging as a central topic in 2011; Levin et al. 2014; Wolff et al. 2014). evolutionary ecology (Sunnucks et al. 2017; Hill Paradoxically, despite the need for the 2019a, 2019b).

Advance Access publication August 24, 2019 ß 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: [email protected]. Beyond the powerhouse 857

The challenge for scientists working to understand using a comparative study of birds and mammals. macro-features of complex life in the context of the Birds have higher basal metabolic rates, higher blood coevolution of mitochondrial and nuclear genes is glucose concentration and longer lifespans than sim- that such investigations demand understanding and ilar sized mammals (Hickey 2008), but the literature technical knowledge of cell and molecular biology as is equivocal on whether oxidative stress is higher in well as whole-organism processes. Traditionally, biol- birds compared with mammals. Jimenez et al. (2019) ogists focused at one of these levels of organization derived values from the literature for the whole- have paid little attention to discoveries made at the animal metabolism of 999 species of birds and other level (Hagen 1999; Hill 2014). The rift between 1130 species of mammals, and then measured cellu- cell and molecular biology and ecology and evolu- lar metabolic rates from primary fibroblast cells of a Downloaded from https://academic.oup.com/icb/article/59/4/856/5542403 by Auburn University user on 30 April 2021 tion reached a peak in the late 20th century when subset of these taxa. They also compared levels of many biology departments at universities fractured oxidative stress in the focal bird and mammal taxa into separate cell/molecular departments and ecol- using separated blood in a group of phylogenetically- ogy/evolution departments, exacerbating a lack of corrected birds and mammals. They found that communication between reductionistic and organis- mass-specific metabolic rates were higher in birds mal biologists. As genomics and other tools for compared with mammals. Using primary fibroblast studying cellular and molecular processes became cells, basal metabolism was significantly lower in more broadly accessible to organismal biologists birds compared with mammals. They measured total and cell and molecular biologists expanded investi- antioxidant capacity using plasma and red blood gations to non-model species, the walls between cell/ cells and found that circulating lipid damage and molecular and ecology/evolution-focused approaches catalase activity were significantly lower in birds to biological study began to erode. compared with mammals. This study underscores It is in the spirit of further eroding division be- the fact that whole-animal phenotypes associated tween bottom-up and top-down approaches to un- with longer lifespan (as those in birds) emerge derstanding the evolution of organisms that we from aerobic cellular processes (oxidative stress) at convened our symposium on the evolutionary con- a cellular level. sequences of mitonuclear coadaptation. Mitonuclear Virtually all studies of mitochondrial function and interactions hold the potential to influence our un- evolution make specific assumptions about the rate derstanding of how major organismal traits evolved and sources of mutations to the mitochondrial DNA across a wide spectrum of biological functions in- (mtDNA). Organismal biologists have long focused cluding physiology, life history, genomic architec- their attention on damage from free radicals (e.g., ture, adaptation, and diversification. The oxidative damage as investigated by Jimenez et al. symposium contributors use cell/molecular tools to 2019), but this is not the sole source of mutations examine the evolution and physiological implications to mtDNA; mutations can also arise via errors dur- of mitonuclear interactions, but then apply these ing the replication of mtDNA. Mitochondrial outcomes to broad questions of organismal ecology turnover—which necessitates mtDNA replication— and evolution. The papers that comprise this volume is independent of the cell cycle, allowing continued of Integrative and Comparative Biology reflect the mitochondrial replacement in post-mitotic tissues pervasive effects and integrative nature of mitonu- and allowing the rate of replacement to exceed the clear coadaptation and coevolution (Table 1). cellular rate in mitotic tissue (Larsson 2010). Turnover rates can be rapid, for example, the half- life of mitochondria in the human liver is only 2 Oxidative stress, mutation, and life days (Miwa et al. 2008). Thus, even with repair history mechanisms in place, the accumulation of mtDNA Eukaryotes rely on mitonuclear communication to mutations is inevitable when mtDNA is copied and set the pace of metabolism both at the level of the copy error can exceed the rate of mtDNA mutation whole organism and within cells. As a consequence, that is caused by oxidative stress (Ameur et al. 2011; whole-organism phenotypes should be related to cel- Kennedy et al. 2013; Itsara et al. 2014). In this issue, lular function (Barja 1998), demonstrating the im- Hood et al. (2019) argue that it is important to con- portance of investigating mitonuclear interactions sider mitochondrial replication error as an important across multiple biological scales. Jimenez et al. contributor to variation in the performance and life- (2019) assess this basic assumption that the “pace span of individuals. mtDNA replication requires co- of life” should be reflected in mitochondrial function ordination between nuclear-encoded polymerases 858 J. C. Havird et al.

Table 1 A summary of the papers that comprise this volume of Integrative and Comparative Biology, demonstrating the integrative and comparative nature of mitonuclear studies

Reference Study (this volume) Type organism(s) Scale(s) Evolutionary topic Conclusion Jimenez et al. Primary Birds, mammals Organismal, cellular, Aging Mt phenotypes may underlie research molecular differences in lifespan Hood et al. Review Eukaryotes Organismal, molecular Mutation rates Mt replication may play a large role in determining mutation rates Weaver Hypothesis Eukaryotes Molecular Complexity, sexual AOX may play roles in key reproduction, evolutionary transitions Downloaded from https://academic.oup.com/icb/article/59/4/856/5542403 by Auburn University user on 30 April 2021 mutation rates Dowling and Adrian Review Eukaryotes Population, organismal, Sex-specific effects Tests of the Mother’s curse cellular, molecular hypothesis require thoroughness Montooth et al. Primary Fruit flies Organismal Sex-specific effects The Mother’s Curse hypoth- research esis receives mixed support in fruit flies Havird and Primary Fruit flies, Molecular Sex-specific effects Mother’s Curse dynamics do McConie research mammals not explain OXPHOS paralog evolution Sullins et al. Primary Nematodes Organismal, molecular Selfishness Mt heteroplasmy is research determined by selection at multiple levels Ramsey et al. Primary Plants Population, organismal, Linkage disequilibrium Selection for heteroplasmy research molecular could mitigate cytonuclear incompatibilities Ghiselli et al. Primary Molluscs Tissue, cellular, molecular Inheritance Meiotic drive may play a role research in the DUI system Sokolova et al. Review Invertebrates Tissue, cellular, molecular Environmental Mitonuclear interactions adaptation may influence hypoxia tolerance McKenzie et al Primary Fishes Population, organismal, Environmental Geographic variation in research cellular, molecular adaptation, mtDNA sequence can be speciation shaped by many factors Hill Review Eukaryotes Population, molecular Speciation Benefits of mt introgression may offset disrupting mitonuclear interactions Tobler et al. Review Eukaryotes Population, molecular Environmental Selection on mt function may adaptation, speciation contribute to reproductive isolation

and mitochondrial-encoded replication cofactors, from the ubiquinone pool to reduce oxygen to water suggesting that the efficacy of mitonuclear interac- (McDonald et al. 2009). AOX is a component of the tions can be key determinants of mitochondrial respiratory chain that is widely distributed among replication-mediated fitness in many organisms. eukaryotes but that is often not integrated into phys- A basic assumption by most biologists studying iological and evolutionary research on mitochondria, mitonuclear coevolution and coadaptation in com- especially in animals where its distribution is patchy. plex life is that the respiratory chain, including com- AOX remains functional under conditions that ren- plexes I, III, and IV, is the only path for aerobic der complex IV unusable. Weaver (2019) focuses on respiration (Hill 2015). As explained in detail by two primary attributes of AOX: it is resistant to sul- Weaver (2019), however, the alternative oxidase fide and its activation prevents excessive free radical (AOX) is an additional nuclear-encoded oxidoreduc- production during stress. He hypothesizes that AOX tase that functions similarly to complex IV of the played a role in the evolution of metazoans from electron transport system in that it uses electrons simpler eukaryotes by allowing for oxidative Beyond the powerhouse 859 metabolism during the transition from a sulfidic to caveats. First, studies to date have generally been an oxygenated ocean of the Neoproterozoic era. limited to just a handful of model systems. Second, Based on links between free radical production and many studies to date have focused on the sex-specific sexual reproduction (Ho¨randl and Speijer 2018) and effects of mitochondrial genotypes on just one or the role of free radicals in mtDNA mutations, he two traits and might, therefore, have failed to detect proposes two additional evolutionary consequences Mother’s Curse effects even when these are present of AOX respiration and its associated decrease in within a population or species. And third, tests of free radical production. AOX could have played a the hypothesis have generally been limited by a lack role in the persistence of a facultative asexual repro- of replication at each of three levels (the number of ductive strategy observed in many early branching mitochondrial genotypes sampled, the number of Downloaded from https://academic.oup.com/icb/article/59/4/856/5542403 by Auburn University user on 30 April 2021 metazoans, and AOX may also be a mediating factor nuclear backgrounds sampled, and replication of in the observed low mutation accumulation rates of the individual genotype); limitations that could also mtDNA in those taxa. The presence or absence of lead to sampling biases and potential errors of infer- AOX (and other components of mitochondrial ma- ence. Dowling and Adrian (2019) conclude their pa- chinery) may, therefore, have implications for key per by outlining a roadmap for future tests of the evolutionary transitions in eukaryote life history Mother’s Curse hypothesis. and evolution. In further support of the Mother’s Curse hypothesis, Montooth et al. (2019) present new data suggesting that males suffer the negative reproductive The Mother’s Curse consequences of mitonuclear incompatibility, and The necessity of tight mitonuclear coadaptation sug- that these effects are temperature and diet sensitive. gests that there should be broad overlap in the inter- However, while the model of mitonuclear incompat- ests of mitochondrial and nuclear genomes in ibility that they present does have sex-specific fitness enabling high organismal function. At the same effects, the magnitude of these effects is frequently time, however, mitochondria are typically maternally larger in females. They suggest that a productive way transmitted (but see Ghiselli et al. 2019) and as a forward in studies of the Mother’s Curse hypothesis consequence, males are typically an evolutionary may be to investigate the physiological capacity for dead end for mitochondrial genes. Theory predicts sex-specific mtDNA and mitonuclear effects in the that maternal inheritance of mtDNA favors the evo- context of recent research documenting extensive lution of male-harming alleles because it renders nat- sexual dimorphism in physiology in the model fruit ural selection blind to mtDNA mutations that harm fly Drosophila melanogaster (Millington and Rideout only males (Cosmides and Tooby 1981; Frank and 2018). In this way, developmental physiology may Hurst 1996; Connallon et al. 2018). Accordingly, illuminate the scope for sex-specific effects of over evolutionary time, it is expected that the mito- mtDNA mutations that are a requirement for the chondrial genome will accumulate a load of male- Mother’s Curse to have ubiquitous effects in harming mutations, manifesting in effects on core populations. components of health and life-history of males, a While Montooth et al. (2019) evaluate organismal phenomenon called the Mother’s Curse (Gemmell phenotypes stemming from Mother’s Curse, Havird et al. 2004). Although over three decades old, there and McConie (2019) consider the role of Mother’s have been few formal tests of this hypothesis, and the Curse in shaping the evolution of nuclear-encoded field has suffered from the absence of a clear predic- oxidative phosphorylation (OXPHOS) paralogs. tive framework. These gene duplicates show remarkable divergence To redress this, here Dowling and Adrian (2019) from each other (50% different in amino acid provide an overview of the Mother’s Curse hypoth- sequence), yet must interact with a single mitochon- esis and explain why the Mother’s Curse process is drial genome. Because many paralogs show testes- most likely to affect traits that exhibit higher levels of specific gene expression, one hypothesis is that sexual dimorphism. They then outline each of three nuclear-encoded OXPHOS duplicates may be a re- key predictions of the Mother’s Curse hypothesis sponse to Mother’s Curse. Testes-specific OXPHOS and discuss experimental approaches for testing these duplicates may be under selection to offset male predictions, focusing on issues of replication and bi- harm caused by Mother’s Curse mutations in the ological scale. They conclude that while studies to mitochondrial genome. Examining data from mam- date have provided important insights into the ca- mals and Drosophila, Havird and McConie (2019) pacity of mitochondrial genomes to accumulate conclude that Mother’s Curse dynamics may not male-harming mutations, these insights come with play a dominant role in shaping the evolution of 860 J. C. Havird et al. testes-specific OXPHOS paralogs. OXPHOS paralogs With heteroplasmy, multiple mitotypes exist were found to be evolving under relaxed selection in within an individual on one nuclear background. Drosophila and a spatial analysis failed to identify When plant mitochondrial genomes undergo recom- mitonuclear contact sites as being particularly likely bination between heteroplasmic variants, new allelic to undergo changes in mammals. Alternative pro- combinations, and thus, mitotypes, may be formed. cesses, independent of mitonuclear interactions, Yet it is presently unknown if heteroplasmy plays a might be more important in shaping the evolution role in patterns of linkage disequilibrium (LD) be- of these highly divergent OXPHOS duplicates. These tween nuclear and mitochondrial genes (i.e., mito- studies highlight how a focus on conflict in mitonu- nuclear LD) and genes within the mitochondrial clear coevolution can increase our understanding of genome (i.e., mito–mito LD) in natural populations. Downloaded from https://academic.oup.com/icb/article/59/4/856/5542403 by Auburn University user on 30 April 2021 sex-specific processes at the organismal and molecu- Ramsey et al. (2019) investigated mitonuclear LD in lar levels. wild carrot from two geographic regions of the USA, a species known to exhibit occasional biparental inheritance and heteroplasmy. They tested for hetero- Heteroplasmy plasmy and LD by analyzing two mitochondrial The Mother’s Curse stems from the uniparental in- genes and simple sequence repeats (SSRs) of 15 nu- heritance of mitochondrial genomes, so why is strict clear genes. They first assayed the mitochondrial maternal inheritance so common in mitochondrial COX1 gene for heteroplasmy. Approximately half genomes? The alternative biparental inheritance cre- of the individuals in each region were heteroplasmic ates a new arena for selfish mitochondria. Having for a silent T/C single nucleotide polymorphism. multiple, variable mitochondrial genomes within an Ramsey et al. (2019) then calculated mitonuclear organism (i.e., heteroplasmy) can create selection for LD for heteroplasmic and homoplasmic individuals competition among different mitochondrial lineages separately and used a Z-transformation test to deter- within an organism at the expense of individual fit- mine whether LD differed between them. They show ness (Haig 2016; Havird et al. 2019). Selfish mtDNA that in one geographical region all five significantly poses a significant challenge to genome integrity, mi- different nuclear SSR–mitotype pairs have higher LD tochondrial function, and organismal fitness. Despite values in heteroplasmic individuals, and in the other implications of selfish mtDNA elements for specia- region five of six significantly different nuclear SSR- tion and other topics in evolutionary biology, the mitotype pairs show the same pattern. They also find forces controlling their formation, age-related accu- that the overall magnitude of LD between COX1 and mulation, and offspring transmission remain largely ATP9 is lower in heteroplasmic individuals in both unknown. Sullins et al. (2019) report the first com- regions, indicating recombination. Should demo- prehensive assessment of naturally-occurring selfish graphic processes disrupt mitonuclear LD and, there- mtDNA dynamics during animal development and fore, interactions, selection for heteroplasmy could transmission utilizing Caenorhabditis briggsae mitigate cytonuclear incompatibilities as hetero- nematodes—a genetic model that can simultaneously plasmy may provide alternative allelic variants to act as a model for pathogenic mitochondrial genome better match with nuclear backgrounds. evolution and inheritance. Natural C. briggsae iso- Considerations of both cooperation and conflict lates harbor varying levels of heteroplasmy (up to between co-functioning mitochondrial and nuclear 60%) for a large-scale deleterious deletion affecting genes become problematic when both sexes can the NADH-dehydrogenase 5 gene. The study’s com- transmit mitochondrial genes to offspring. In this parisons of deletion heteroplasmy levels between regard, Ghiselli et al. (2019) provide new and fasci- parents and offspring were indicative of considerable nating data on the evolutionary consequences of bi- purifying selection operating to maintain mtDNA parental transmission of mitochondria. They studied genome integrity between generations. However, bivalves with doubly uniparental inheritance (DUI), other results implicated mitonuclear interaction as a condition in which two mitochondrial lineages are a likely contributor to observed among-isolate differ- present: one following a matrilinear inheritance (F- ences in patterns of both mtDNA deletion transmis- type) and the other following a patrilinear inheri- sion and age-related accumulation. Taken together, tance (M-type). DUI has been reported so far in the results imply that natural mtDNA deletion fre- 100 bivalve species. Due to such distinct transmis- quencies are likely defined by a balance between re- sion patterns, the mitochondrial OXPHOS proteins current deletion formation as well as selection can reach an amino acid sequence divergence of 52% occurring at gametic and individual levels, all of between the F- and M-lineages in the same species. which may be influenced by mitonuclear interplay. Such divergence, coupled with the natural Beyond the powerhouse 861 heteroplasmy of some tissues, provides a unique op- gradients or by intrinsic factors such as mitonuclear portunity to study mitochondrial inheritance, mito- incompatibilities. Distinguishing among these poten- nuclear interactions, and mitochondrial activity in tially interacting possibilities requires an integrated the germline (Milani and Ghiselli 2015). Ghiselli approach combining population genomic data for et al. (2019) visualized, for the first time, F- and both the mitochondrial and nuclear genomes and M-type mitochondrial proteins in the germline and assessments of mitochondrial function. Atlantic kil- somatic tissues of the DUI species Ruditapes philip- lifish provides a case study where all of these types of pinarum and found heteroplasmy at the organelle data are available. There is a steep cline in mtDNA level in undifferentiated germ cells of both sexes in this species, through an environmental tempera- and in male soma. On the contrary, as expected, ture gradient along the Atlantic coast of North Downloaded from https://academic.oup.com/icb/article/59/4/856/5542403 by Auburn University user on 30 April 2021 mature gametes turned out to be homoplasmic for America. There is substantial evidence for the role the respective sex-specific lineage (F-type in eggs, M- of neutral demographic forces such as secondary type in sperm). This finding supports a previously contact in shaping this cline, but there is also evi- advanced hypothesis, according to which the transi- dence of putatively adaptive differentiation in mito- tion from heteroplasmy to homoplasmy would be chondrial function. Population genomic data reveal due to a process of meiotic drive (Milani et al. signals of weak selection, and potential evidence of 2015, 2016). In the light of the new data, Ghiselli mitonuclear incompatibility, but overall this case et al. (2019) propose a revised model for the DUI study highlights the challenges of distinguishing the system, discussing the interactions of mitochondria various factors that can shape geographic variation with germ plasm and their role in germline in mtDNA sequence. This highlights the importance development. of integrated studies of mitochondrial ecophysiology.

Environmental adaptation Speciation The coevolution of the mitochondrial and nuclear Uniparental inheritance and selection pressures act genomes not only maintains current metabolic ca- to maintain the tightly coordinated activity of nu- pacities in a population of organisms, but novel clear and mitochondrial genes. For this reason, al- mitonuclear combinations can also potentially facil- though these genomes are physically distinct from itate adaptation to the environment including envi- one another, alleles within them are often found in ronments that would otherwise induce stress. LD within a population (i.e., mitonuclear LD). This Sokolova et al. (2019) discuss the known and puta- tight linkage is thought to be a consequence of co- tive mechanisms involved in mitochondrial tolerance adaptation between nuclear and mitochondrial to fluctuating oxygen conditions in hypoxia tolerant genomes within organisms. Divergence in uniquely organisms (predominantly ectotherms). Oxygen fluc- coadapted sets of mt and N-mt genes is proposed to tuations are an ultimate mitochondrial stressor, and be a process of speciation (Gershoni et al. 2009; adaptations to hypoxia involve mechanisms that Burton and Barreto 2012; Hill 2016, 2017). This hy- maintain mitochondrial integrity and protein ho- pothesis clearly predicts that there should be little meostasis, regulate O2 flux and redox balance during flow of mitochondrial genotypes between species hypoxia, and ensure rapid recovery of the OXPHOS (Sloan et al. 2017). The observation of rampant re- capacity upon reoxygenation. These adaptations replacement of the mitochondrial genotype of one spe- quire concerted adjustments in mitochondrial- and cies with the mitochondrial genotype of another nuclear-encoded proteins, suggesting that mitonu- species, particularly when there is little or no change clear interactions might play a key role in evolution in the nuclear genotypes of either the donor or re- of hypoxia tolerance. However, this aspect of mito- cipient taxa (Toews and Brelsford 2012), poses a nuclear interactions is currently understudied. major challenge to the mitonuclear compatibility In the context of environmental adaptation, species concept. Hill (2019b) reviews the evidence McKenzie et al. (2019) studied clines in mitochon- for rampant mitochondrial introgression and drial genotypes in the Atlantic killifish (Fundulus presents hypotheses for potential benefits of mito- heteroclitus). Such clines in mtDNA can be produced chondrial introgression that could theoretically offset as a result of a variety of processes. They are some- the costs of loss of tight mitonuclear coadaptation. times the result of neutral processes such as second- Tobler et al. (2019) further consider a role for ary contact or sex-biased gene flow. But they can mitonuclear genomic interactions in the process of also be the product of extrinsic selection driven by speciation by presenting an overview of the various benefits of local adaptation along environmental mechanisms by which mitochondria could 862 J. C. Havird et al. contribute to the evolution of reproductive isolation Society, and the Divisions of Comparative during ecological speciation. They emphasize cases Physiology and Biochemistry, Invertebrate Zoology, where divergent selection on mitochondrial function and Phylogenetics and Comparative Biology. R.J.W. between closely related lineages might be expected to and G.E.H. were funded by a National Science contribute to the formation of various reproductive Foundation Doctoral Dissertation Improvement isolating barriers as a byproduct of adaptation. They Grant (NSF-IOS-1701827). highlight key gaps in understanding of the importance and generality of mitochondrially-mediated reproductive isolation at various stages of the Reference speciation process and how such mechanisms inter- Ameur A, Stewart JB, Freyer C, Hagstro¨m E, Ingman M, Downloaded from https://academic.oup.com/icb/article/59/4/856/5542403 by Auburn University user on 30 April 2021 act with other reproductive isolation barriers. They Larsson N-G, Gyllensten U. 2011. Ultra-deep sequencing conclude that approaches to the study of mitonu- of mouse mitochondrial DNA: mutational patterns and clear speciation that include experimental evolution their origins. PLoS Genet 7:e1002028. 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Naturalists, molecular biologists, and the presenters at the symposium for their valued contri- challenges of molecular evolution. J Hist Biol 32:321–41. butions: D. Rand, J. Mossman, H. Bedwell, N. Teets, Haig D. 2016. Intracellular evolution of mitochondrial DNA (mtDNA) and the tragedy of the cytoplasmic commons. K. Nitepold,~ H. Taylor, N. Rank, R. Adrian, N. Barts, Bioessays 38:549–55. O. Matoo, A. Graham, R. Vaught, L. Kvistad, N. Havird J, Forsythe E, Williams A, Werren J, Dowling D, Sloan Jayasundara, H. Parry, R. Klabacka, and A. D. 2019. Selfish mitonuclear conflict. Curr Biol 29:R496- Dhawanjewar. R511. Havird JC, McConie HJ. 2019. Sexually antagonistic mitonu- Funding clear coevolution in duplicate oxidative phosphorylation genes. Integr Comp Biol (doi: 10.1093/icb/icz021). Support for the symposium was provided by the Hickey A. 2008. Avian mtDNA diversity?: an alternate expla- National Science Foundation (IOS-1839203), the nation for low mtDNA diversity in birds: an age-old solu- Company of Biologists (EA1694), The Crustacean tion? Heredity (Edinb) 100:443–3. Beyond the powerhouse 863

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