Mitochondrial Genotypes Research Articles

Entomological time travel: reconstructing the invasion history of the buckeye butterflies (genus Junonia) from Florida, USA

Invasion biology examines the process by which non-native species integrate into new habitats. Three species of buckeye butterflies (genus Junonia) currently occur in Florida, USA, including Junonia coenia (polyphagous and widely distributed), J. neildi (monophagous and restricted to coastal areas), and J. zonalis (polyphagous tropical species restricted to frost-free South Florida). Two species have long been resident in Florida, whereas J. zonalis was first detected in Florida in 1981. Diagnostic morphological and molecular markers exist for determining Junonia with Caribbean ancestry, allowing observation of the invasion and creation of a secondary contact zone over space and time. We developed techniques to quickly, inexpensively, and unambiguously determine mitochondrial genotypes from museum specimens collected in Florida and the Caribbean over the last 150 years. We reconstructed the invasion of J. zonalis as it colonized Florida using 816 Junonia museum specimens from 1866 to 2016, including some of the oldest insect museum specimens ever genotyped. Significant correlations were found between the presence of Caribbean genotypes and latitude, longitude, and time. Junonia zonalis likely colonized Florida from Cuba by the 1930s, followed by hybridization with resident species, with ongoing genetic exchange between Cuba and the Florida Keys. Episodic gene flow between Florida Keys and mainland populations of J. zonalis may also be occurring. Mainland mitochondrial genotypes appear to be more resilient to extreme high and low temperatures than Caribbean genotypes. This time series in Junonia can be used as a model for understanding the process of adaptation required for successful invasion of new habitats.

Genetic Origin of the Two Galápagos Tortoises in the Ueno Zoo, Japan Based on Mitochondrial DNA Sequences

Galapagos tortoises are a symbolic animal in terms of conservation biology as well as evolutionary biology, and both in situ and ex situ conservation programs are currently underway. For endangered species, captive individuals can perform a certain role as genetic reservoirs for ongoing and future breeding programs We examined the genetic identities of two giant tortoises in Ueno Zoo, Japan. The mitochondrial genotype of the older tortoise, Taro, as appeared to be that of Chelonoidis porteri from Santa Cruz island. The mitochondrial genotype of the younger tortoise, Kamekichi, was identified as either C. becki from the northern area of Isabela island, or C. darwini from Santiago island. These genetic analyses serve as reference data for the future conservation management of captive Galapagos tortoises.

Spatial genetics of a high elevation lineage of Rhytididae land snails in New Zealand: the Powelliphanta Kawatiri complex

ABSTRACTPowelliphanta is a genus of large carnivorous land snails endemic to New Zealand which display phenotypic variation within comparatively small geographic distances. The diversity within these snails has become a matter of high interest to conservation, as many lineages occupy small (or highly fragmented) ranges that render them vulnerable to ongoing habitat loss and predation by exotic pests. Combining Powelliphanta mitochondrial sequence data and genotypes of microsatellite loci we document the genetic structure within a species complex dubbed ‘Kawatiri’. All populations (with one exception) within the Kawatiri lineage are restricted to subalpine habitat (at elevations over 600 m above sea level). The ranges of some Kawatiri complex populations are adjacent to the congeneric lowland species Powelliphanta lignaria. Improved understanding of the distribution of this complex and the level and structure of genetic diversity provided a picture of a naturally fragmented lineage, restricted to a particular ecological zone. We identified six genetic clusters associated with population connectivity orientated north–south along mountain ranges, with east–west divisions between ranges. Future management should aim to retain the evolutionary potential within this young radiation by actively conserving the variation encompassed by each of the six clusters identified here.

Genetic identification of native populations of Mediterranean brown trout Salmo trutta L. complex (Osteichthyes: Salmonidae) in central Italy

Italian native populations of Mediterranean brown trout belong to the Salmo trutta complex. This species complex includes many mitochondrial lineages and phenotypes that have caused taxonomic controversies over time. The spatial distribution and the genetic diversity of these fishes are threatened by habitat destruction, global warming and, mainly, by the introduction of domestic trout of Atlantic origin. Indeed allochthonous trouts were massively restocked in Italian rivers for a century and they admixed with native populations. In order to identify residual native populations of Mediterranean brown trout, a genetic analysis of specimens collected within Latium region, on the Tyrrhenian slope of central Italy, was undertaken. To this purpose, 210 trout specimens were collected from six different rivers and analyzed for the identification of their nuclear (LDH-C1* RFLP) and mitochondrial (Control Region sequences) genotypes. Genetic characterization with these molecular markers allowed a quantitative estimate of allochthonous genotypes, which are present in all brown trout populations of the six sites, even if not equally distributed across the sampling area. At least three populations, inhabiting diverse lotic ecosystems (mountain, hilly and coastal streams respectively), are characterized by a high percentage of native nuclear allele *100 at locus LDH-C1* and typical Mediterranean haplotypes (of AD and ME lineages), which can be considered as different management units (MUs). This finding highlighted the aquatic ecosystems of the Latium Region as an important hotspot of salmonid biodiversity within the Italian peninsula, with important implications from a conservation perspective.

Assessing the fitness consequences of mitonuclear interactions in natural populations.

Metazoans exist only with a continuous and rich supply of chemical energy from oxidative phosphorylation in mitochondria. The oxidative phosphorylation machinery that mediates energy conservation is encoded by both mitochondrial and nuclear genes, and hence the products of these two genomes must interact closely to achieve coordinated function of core respiratory processes. It follows that selection for efficient respiration will lead to selection for compatible combinations of mitochondrial and nuclear genotypes, and this should facilitate coadaptation between mitochondrial and nuclear genomes (mitonuclear coadaptation). Herein, we outline the modes by which mitochondrial and nuclear genomes may coevolve within natural populations, and we discuss the implications of mitonuclear coadaptation for diverse fields of study in the biological sciences. We identify five themes in the study of mitonuclear interactions that provide a roadmap for both ecological and biomedical studies seeking to measure the contribution of intergenomic coadaptation to the evolution of natural populations. We also explore the wider implications of the fitness consequences of mitonuclear interactions, focusing on central debates within the fields of ecology and biomedicine.

Mitochondrial Genome Variation Affects Multiple Respiration and Nonrespiration Phenotypes in Saccharomyces cerevisiae.

Mitochondrial genome variation and its effects on phenotypes have been widely analyzed in higher eukaryotes but less so in the model eukaryote Saccharomyces cerevisiae Here, we describe mitochondrial genome variation in 96 diverse S. cerevisiae strains and assess associations between mitochondrial genotype and phenotypes as well as nuclear-mitochondrial epistasis. We associate sensitivity to the ATP synthase inhibitor oligomycin with SNPs in the mitochondrially encoded ATP6 gene. We describe the use of iso-nuclear F1 pairs, the mitochondrial genome equivalent of reciprocal hemizygosity analysis, to identify and analyze mitochondrial genotype-dependent phenotypes. Using iso-nuclear F1 pairs, we analyze the oligomycin phenotype-ATP6 association and find extensive nuclear-mitochondrial epistasis. Similarly, in iso-nuclear F1 pairs, we identify many additional mitochondrial genotype-dependent respiration phenotypes, for which there was no association in the 96 strains, and again find extensive nuclear-mitochondrial epistasis that likely contributes to the lack of association in the 96 strains. Finally, in iso-nuclear F1 pairs, we identify novel mitochondrial genotype-dependent nonrespiration phenotypes: resistance to cycloheximide, ketoconazole, and copper. We discuss potential mechanisms and the implications of mitochondrial genotype and of nuclear-mitochondrial epistasis effects on respiratory and nonrespiratory quantitative traits.

Phylogeographic and diversification patterns of the white-nosed coati (Nasua narica): Evidence for south-to-north colonization of North America

White-nosed coatis (Nasua narica) are widely distributed throughout North, Central, and South America, but the patterns of temporal and spatial diversification that have contributed to this distribution are unknown. In addition, the biogeographic history of procyonid species in the Americas remains contentious. Using sequences from three mitochondrial loci (Cytochrome b, NAHD5 and 16S rRNA; 2201 bp) and genotypes from 11 microsatellite loci, we analyzed genetic diversity to determine phylogeographic patterns, genetic structure, divergence times, and gene flow among Nasua narica populations throughout the majority of the species’ range. We also estimated the ancestral geographic range of N. narica and other procyonid species. We found a high degree of genetic structure and divergence among populations that conform to five evolutionarily significant units. The most southerly distributed population (Panama) branched off much earlier (∼3.8 million years ago) than the northern populations (<1.2 million years ago). Estimated gene flow among populations was low and mostly northwards and westwards. The phylogeographic patterns within N. narica are associated with geographic barriers and habitat shifts likely caused by Pliocene-Pleistocene climate oscillations. Significantly, our findings suggest the dispersal of N. narica was south-to-north beginning in the Pliocene, not in the opposite direction during the Pleistocene as suggested by the fossil record, and that the most recent common ancestor for coati species was most likely distributed in South or Central America six million years ago. Our study implies the possibility that the diversification of Nasua species, and other extant procyonid lineages, may have occurred in South America.

Maternal age effects on fecundity and offspring egg-to-adult viability are not affected by mitochondrial haplotype.

While numerous studies have demonstrated that mitochondrial genetic variation can shape organismal phenotype, the level of contribution the mitochondrial genotype makes to life‐history phenotype across the life course remains unknown. Furthermore, a clear technical bias has emerged in studies of mitochondrial effects on reproduction, with many studies conducted on males, but few on females. Here, we apply a classic prediction of the evolutionary theory of aging to the mitochondrial genome, predicting the declining force of natural selection with age will have facilitated the accumulation of mtDNA mutations that confer late‐life effects on female reproductive performance. This should lead to increased levels of mitochondrial genetic variation on reproduction at later‐life stages. We tested this hypothesis using thirteen strains of Drosophila melanogaster that each possessed a different mitochondrial haplotype in an otherwise standard nuclear genetic background. We measured fecundity and egg‐to‐adult viability of females over five different age classes ranging from early to late life and quantified the survival of females throughout this time period. We found no significant variation across mitochondrial haplotypes for the reproductive traits, and no mitochondrial effect on the slope of decline in these traits with increasing age. However, we observed that flies that died earlier in the experiment experienced steeper declines in the reproductive traits prior to death, and we also identified maternal and grandparental age effects on the measured traits. These results suggest the mitochondrial variation does not make a key contribution to shaping the reproductive performance of females.

Origin of the widely and discontinuously distributed mitochondrial genotypes of Oryzias latipes: introduced or native genotypes?

A mitochondrial cytochrome b genotype of Oryzias latipes, “mitotype B15”, is widely and discontinuously distributed in various localities in Japan. To re-examine the origin of mitotype B15 detected in various localities, we conducted a sequence analysis of the NADH dehydrogenase subunit 2 (ND2) gene region. Twenty-eight haplotypes were defined among mitotype B15 fish from 23 localities throughout Japan. Most of the haplotypes detected in each area are unique to the location and genetically closely related to each other, indicating that they are native haplotypes. Our results suggest that ND2 analysis is important for identifying native populations of O. latipes.

Functional Divergence of Mitochondria and Coevolution of Genomes: Cool Mitochondria in Hot Lizards.

Mitochondria play a key role in the ecology and evolution of species through their influence on aerobic metabolism. Mitochondrial DNA (mtDNA) and nuclear genomes must interact for optimal functioning of oxidative phosphorylation to produce ATP, and breakdown of coadaptation components from each may have important evolutionary consequences for hybridization. Introgression of mitochondria in natural populations through hybridization with unidirectional backcrossing allows the testing of coadaptation of mitochondria to different nuclear backgrounds. We compared the function of mitochondria isolated from two species of Urosaurus lizards and hybrid populations. Due to past introgression, hybrids contain the nuclear genome of the "hot-adapted" species (U. graciosus) but the mtDNA of the less heat-tolerant species (U. ornatus). It was found that the function of the parental forms of mitochondria had significantly diverged with the hot-adapted species. There was significant genotype × genotype × environment interactions for mitochondrial membrane potential and genotype × genotype interactions for ATP production. Membrane potential decreased less at a higher temperature, while ATP production was higher at both temperatures in introgressed mitochondria. Oxygen consumption was lower in U. graciosus than in U. ornatus parental-type mitochondria, indicating a likely response to living in hotter environments. Respiratory control ratio values, which provide an indication of the functional quality of isolated mitochondria, were lower in introgressed mitochondria than in parental U. ornatus types, indicating a negative impact on biological function in introgressed mitochondria.

Effects of the Mitochondrial and Nuclear Genomes on Nonshivering Thermogenesis in a Wild Derived Rodent.

A key adaptation of mammals to their environment is their ability to maintain a constant high body temperature, even at rest, under a wide range of ambient temperatures. In cold climates, this is achieved by an adaptive production of endogenous heat, known as nonshivering thermogenesis (NST), in the brown adipose tissue (BAT). This organ, unique to mammals, contains a very high density of mitochondria, and BAT correct functioning relies on the correct functioning of its mitochondria. Mitochondria enclose proteins encoded both in the maternally inherited mitochondrial genome and in the biparentally inherited nuclear genome, and one overlooked hypothesis is that both genomes and their interaction may shape NST. By housing under standardized conditions wild-derived common voles (Microtus arvalis) from two distinct evolutionary lineages (Western [W] and Central [C]), we show that W voles had greater NST than C voles. By introgressing those two lineages over at least nine generations, we then experimentally tested the influence of the nuclear and mitochondrial genomes on NST and related phenotypic traits. We found that between-lineage variation in NST and BAT size were significantly influenced by the mitochondrial and nuclear genomes, respectively, with the W mitochondrial genotype being associated with higher NST and the W nuclear genotype with a larger BAT. There were significant mito-nuclear interactions on whole animal body weight and resting metabolic rate (RMR). Hybrid voles were lighter and had higher RMR. Overall, our findings turn new light on the influence of the mitochondrial and nuclear genomes on thermogenesis and building adaptation to the environment in mammals.

Molecular marker sequences of cattle Cooperia species identify Cooperia spatulata as a morphotype of Cooperia punctata.

The genus Cooperia includes important parasites of ruminants and currently contains 34 accepted species. However, even for those species infecting livestock, there is a considerable lack of molecular information and many species are only identifiable using subtle morphological traits. The present study aimed to provide molecular data to allow diagnosis of Cooperia species infecting cattle. Partial sequences of two mitochondrial (cytochrome oxidase 2, 12S rRNA gene) and two nuclear genes (isotype 1 β tubulin gene including two introns, internal transcribed spacers (ITS) were obtained from morphologically identified specimens of Cooperia pectinata, Cooperia punctata and Cooperia spatulata as well as from larvae of pure Cooperia oncophora and C. punctata laboratory isolates. Pairwise identity of ITS-2 sequences was very high and it was the only region able to identify a specimen as Cooperia sp. However, the ITS-2 was unreliable for diagnosis at the species level. All other marker sequences could not unequivocally be allocated to the genus Cooperia but allowed clear species identification with the exception of the pair C. punctata/C. spatulata for which no significant differences were found for any marker sequence. Maximum-likelihood phylogenetic analyses of individual genes as well as a multi-locus analysis covering all four sequences confirmed that specimen identified as C. spatulata were randomly distributed throughout the C. punctata cluster and formed no group of their own. In contrast, the other Cooperia species formed clearly separated and statistically supported clusters. These data indicate that C. spatulata is most likely only a morphotype of C. punctata and the name should be considered a synonym. Combinations of nuclear and mitochondrial markers should be used to identify morphotypes or cryptic species to benefit from excellent barcoding properties of the latter but allowing proper phylogenetic analyses and controlling for lineage sorting that might occur for mitochondrial genotypes within a species.

Population structure of North Atlantic and North Pacific sei whales (Balaenoptera borealis) inferred from mitochondrial control region DNA sequences and microsatellite genotypes

Currently, three stocks of sei whales (Balaenoptera borealis) are defined in the North Atlantic; the Nova Scotian, Iceland-Denmark Strait and Eastern North Atlantic stocks, which are mainly based upon historical catch and sighting data. We analyzed mitochondrial control region DNA (mtDNA) sequences and genotypes from 7 to 11 microsatellite loci in 87 samples from three sites in the North Atlantic; Iceland, the Gulf of Maine and the Azores, and compared against the North Pacific using 489 previously published samples. No statistically significant deviations from homogeneity were detected among the North Atlantic samples at mtDNA or microsatellite loci. The genealogy estimated from the mtDNA sequences revealed a clear division of the haplotypes into a North Atlantic and a North Pacific clade, with the exception of one haplotype detected in a single sample from the Azores, which was included in the North Pacific clade. Significant genetic divergence between the North Atlantic and North Pacific Oceans was detected (mtDNA ΦST = 0.72, microsatellite Weir and Cockerham’s ϴ = 0.20; p < 0.001). The coalescent-based estimate of the population divergence time between the North Atlantic and North Pacific populations from the sequence variation among the mtDNA sequences was at 163,000 years ago. However, the inference was limited by an absence of samples from the Southern Hemisphere and uncertainty regarding mutation rates and generation times. The estimates of inter-oceanic migration rates were low (Nm at 0.007 into the North Pacific and at 0.248 in the opposite direction). Although estimates of genetic divergence among the current North Atlantic stocks were low and consistent with the extensive range of movement observed in satellite tagged sei whales, the high uncertainty of the genetic divergence estimates precludes rejection of multiple stocks in the North Atlantic.

Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium

To describe the clinical features of a unique pigmentary maculopathy noted in the setting of chronic exposure to pentosan polysulfate sodium (PPS), a therapy for interstitial cystitis (IC). Retrospective case series. Six adult patients evaluated by a single clinician between May 1, 2015, and October 1,2017. Patients were identified by query of the electronic medical record system. Local records were reviewed, including results of the clinical examination, retinal imaging, and visual function assessment with static perimetry and electroretinography. Molecular testing assessed for known macular dystrophy and mitochondrial cytopathy genotypes. Mean best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution units), median cumulative PPS exposure, subjective nature of the associated visual disturbance, qualitative examination and imaging features, and molecular testing results. The median age at presentation was 60 years (range, 37-62 years). All patients received PPS for a diagnosis of IC, with a median cumulative exposure of 2263 g (range, 1314-2774 g), over a median duration of exposure of 186 months (range, 144-240 months). Most patients (4 of 6) reported difficulty reading as the most bothersome symptom. Mean BCVA was 0.1±0.18 logarithm of the minimum angle of resolution. On fundus examination, nearly all eyes showed subtle paracentral hyperpigmentation at the level of the retinal pigment epithelium (RPE) with a surrounding array of vitelliform-like deposits. Four eyes of 2 patients showed paracentral RPE atrophy, and no eyes demonstrated choroidal neovascularization. Multimodal retinal imaging demonstrated abnormality of the RPE generally contained in a well-delineated area in the posterior pole. None of the 4 patients who underwent molecular testing of nuclear DNA returned a pathogenic mutation. Additionally, all 6 patients showed negative results for pathogenic variants in the mitochondrial gene MTTL1. We describe a novel and possibly avoidable maculopathy associated with chronic exposure to PPS. Patients reported symptoms of difficulty reading and prolonged dark adaptation despite generally intact visual acuity and subtle funduscopic findings. Multimodal imaging and functional studies are suggestive of a primary RPE injury. Additional investigation is warranted to explore causality further.

Global phylogeography and genetic diversity of the zoonotic tapeworm Echinococcus granulosus sensu stricto genotype G1

Echinococcus granulosus sensu stricto (s.s.) is the major cause of human cystic echinococcosis worldwide and is listed among the most severe parasitic diseases of humans. To date, numerous studies have investigated the genetic diversity and population structure of E. granulosus s.s. in various geographic regions. However, there has been no global study. Recently, using mitochondrial DNA, it was shown that E. granulosus s.s. G1 and G3 are distinct genotypes, but a larger dataset is required to confirm the distinction of these genotypes. The objectives of this study were to: (i) investigate the distinction of genotypes G1 and G3 using a large global dataset; and (ii) analyse the genetic diversity and phylogeography of genotype G1 on a global scale using near-complete mitogenome sequences. For this study, 222 globally distributed E. granulosus s.s. samples were used, of which 212 belonged to genotype G1 and 10 to G3. Using a total sequence length of 11,682 bp, we inferred phylogenetic networks for three datasets: E. granulosus s.s. (n = 222), G1 (n = 212) and human G1 samples (n = 41). In addition, the Bayesian phylogenetic and phylogeographic analyses were performed. The latter yielded several strongly supported diffusion routes of genotype G1 originating from Turkey, Tunisia and Argentina. We conclude that: (i) using a considerably larger dataset than employed previously, E. granulosus s.s. G1 and G3 are indeed distinct mitochondrial genotypes; (ii) the genetic diversity of E. granulosus s.s. G1 is high globally, with lower values in South America; and (iii) the complex phylogeographic patterns emerging from the phylogenetic and geographic analyses suggest that the current distribution of genotype G1 has been shaped by intensive animal trade.

A systematic review and meta-analysis reveals pervasive effects of germline mitochondrial replacement on components of health.

Mitochondrial replacement, a form of nuclear transfer, has been proposed as a germline therapy to prevent the transmission of mitochondrial diseases. Mitochondrial replacement therapy has been licensed for clinical application in the UK, and already carried out in other countries, but little is known about negative or unintended effects on the health of offspring born using this technique. Studies in invertebrate models have used techniques that achieve mitochondrial replacement to create offspring with novel combinations of mitochondrial and nuclear genotype. These have demonstrated that the creation of novel mitochondrial-nuclear interactions can lead to alterations in offspring characteristics, such as development rates, fertility and longevity. However, it is currently unclear whether such interactions could similarly affect the outcomes of vertebrate biomedical studies, which have sought to assess the efficacy of the replacement therapy. This systematic review addresses whether the effects of mitochondrial replacement on offspring characteristics differ in magnitude between biological (conducted on invertebrate models, with an ecological or evolutionary focus) and biomedical studies (conducted on vertebrate models, with a clinical focus). Studies were selected based on a key-word search in 'Web of Science', complemented by backward searches of reviews on the topic of mitochondrial-nuclear (mito-nuclear) interactions. In total, 43 of the resulting 116 publications identified in the search contained reliable data to estimate effect sizes of mitochondrial replacement. We found no evidence of publication bias when examining effect-size estimates across sample sizes. Mitochondrial replacement consistently altered the phenotype, with significant effects at several levels of organismal performance and health, including gene expression, anatomy, metabolism and life-history. Biomedical and biological studies, while differing in the methods used to achieve mitochondrial replacement, showed only marginally significant differences in effect-size estimates (-0.233 [CI: -0.495 to -0.011]), with larger effect-size estimates in biomedical studies (0.697 [CI: 0.450-0.956]) than biological studies (0.462 [CI: 0.287-0.688]). Humans showed stronger effects than other species. Effects of mitochondrial replacement were also stronger in species with a higher basal metabolic rate. Based on our results, we conducted the first formal risk analysis of mitochondrial replacement, and conservatively estimate negative effects in at least one in every 130 resulting offspring born to the therapy. Our findings suggest that mitochondrial replacement may routinely affect offspring characteristics across a wide array of animal species, and that such effects are likely to extend to humans. Studies in invertebrate models have confirmed mito-nuclear interactions as the underpinning cause of organismal effects following mitochondrial replacement. This therefore suggests that mito-nuclear interactions are also likely to be contributing to effects seen in biomedical studies, on vertebrate models, whose effect sizes exceeded those of biological studies. Our results advocate the use of safeguards that could offset any negative effects (defining any unintended effect as being negative) mediated by mito-nuclear interactions following mitochondrial replacement in humans, such as mitochondrial genetic matching between donor and recipient. Our results also suggest that further research into the molecular nature of mito-nuclear interactions would be beneficial in refining the clinical application of mitochondrial replacement, and in establishing what degree of variation between donor and patient mitochondrial DNA haplotypes is acceptable to ensure 'haplotype matching'.

Mitonuclear Mate Choice: A Missing Component of Sexual Selection Theory?

The fitness of a eukaryote hinges on the coordinated function of the products of its nuclear and mitochondrial genomes in achieving oxidative phosphorylation (OXPHOS). I propose that sexual selection plays a key role in the maintenance of mitonuclear coadaptation across generations because it enables pre-zygotic sorting for coadapted mitonuclear genotypes. At each new generation, sexual reproduction creates new combinations of nuclear and mitochondrial genes, and the potential arises for mitonuclear incompatibilities and reduced fitness. In reviewing the literature, I hypothesize 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. A number of testable predictions emerge from this mitonuclear compatibility hypothesis of sexual selection.

Mitochondrial DNA, nuclear context, and the risk for carcinogenesis.

The inheritance of mitochondrial DNA (mtDNA) from mother to child is complicated by differences in the stability of the mitochondrial genome. Although the germ line mtDNA is protected through the minimization of replication between generations, sequence variation can occur either through mutation or due to changes in the ratio between distinct genomes that are present in the mother (known as heteroplasmy). Thus, the unpredictability in transgenerational inheritance of mtDNA may cause the emergence of pathogenic mitochondrial and cellular phenotypes in offspring. Studies of the role of mitochondrial metabolism in cancer have a long and rich history, but recent evidence strongly suggests that changes in mitochondrial genotype and phenotype play a significant role in the initiation, progression and treatment of cancer. At the intersection of these two fields lies the potential for emerging mtDNA mutations to drive carcinogenesis in the offspring. In this review, we suggest that this facet of transgenerational carcinogenesis remains underexplored and is a potentially important contributor to cancer. Environ. Mol. Mutagen. 60:455-462, 2019. © 2018 Wiley Periodicals, Inc.

Genetic diversity and population structure in the Barrens Topminnow (Fundulus julisia): implications for conservation and management of a critically endangered species

The Barrens Topminnow (Fundulus julisia) has undergone a rapid and dramatic decline. In the 1980s, at least twenty localities with Barrens Topminnows were known to exist in the Barrens Plateau region of middle Tennessee; currently only three areas with natural (not stocked) populations remain. The long-term survival of the Barrens Topminnow will depend entirely on effective management and conservation efforts. Captive propagation and stocking of captive-reared juveniles to suitable habitats have successfully established a handful of self-sustaining populations. However, very little is known about the genetic composition of source and introduced populations including levels of genetic diversity and structuring of genetic variation. Here we use both mitochondrial sequence data and genotypes from 14 microsatellite loci to examine patterns of genetic variation among ten sites, including all sites with natural populations and a subset of sites with introduced (stocked) populations of this species. Mitochondrial sequence analysis reveals extremely low levels of variation within populations and fixed differences between drainages. Microsatellite genotype data shows higher levels of genetic variability and a molecular signature consistent with a recent history of population bottlenecks. Measures of genetic diversity at microsatellite loci including allelic richness are similar within source and introduced populations. Bayesian assignment tests and analysis of molecular variation (AMOVA) support two distinct populations, consistent with drainage boundaries. Results from AMOVA analysis also suggest low levels of genetic connectivity between isolated populations within the same drainage. Here we propose two distinct evolutionary significant units (ESUs) and two management units that reflect this population substructure and warrant consideration in future management efforts.

Frequent heteroplasmy and recombination in the mitochondrial genomes of the basidiomycete mushroom Thelephora ganbajun

In the majority of sexual eukaryotes, the mitochondrial genomes are inherited uniparentally. As a result, individual organisms are homoplasmic, containing mitochondrial DNA (mtDNA) from a single parent. Here we analyzed the mitochondrial genotypes in Clade I of the gourmet mushroom Thelephora ganbajun from its broad geographic distribution range. A total of 299 isolates from 28 geographic locations were sequenced at three mitochondrial loci: the mitochondrial small ribosomal RNA gene, and the cytochrome c oxidase subunits I (COX1) and III (COX3) genes. Quantitative PCR analyses showed that the strains had about 60–160 copies of mitochondrial genomes per cell. Interestingly, while no evidence of heteroplasmy was found at the 12S rRNA gene, 262 of the 299 isolates had clear evidence of heterogeneity at either the COX1 (261 isolates) or COX3 (12 isolates) gene fragments. The COX1 heteroplasmy was characterized by two types of introns residing at different sites of the same region and at different frequencies among the isolates. Allelic association analyses of the observed mitochondrial polymorphic nucleotide sites suggest that mtDNA recombination is common in natural populations of this fungus. Our results contrast the prevailing view that heteroplasmy, if exists, is only transient in basidiomycete fungi.