mtDNA Sequence Variation Research Articles

Mitochondrial DNA Variant for Complex I Reveals a Role in Diabetic Cardiac Remodeling

Myocardial remodeling and dysfunction are serious complications of type 2 diabetes mellitus (T2DM). Factors controlling their development are not well established. To specifically address the role of the mitochondrial genome, we developed novel conplastic rat strains, i.e. strains with the same nuclear genome but a different mitochondrial genome. The new animals were named T2DN(mtFHH) and T2DN(mtWistar), where the acronym T2DN denotes their common nuclear genome (type 2 diabetic nephropathy (T2DN) rats) and mtFHH or mtWistar the origin of their mitochondria, Fawn Hooded Hypertensive (FHH) or Wistar rats, respectively. The T2DN(mtFHH) and T2DN(mtWistar) showed a similar progression of diabetes as determined by HbA1c, cholesterol, and triglycerides with normal blood pressure, thus enabling investigation of the specific role of the mitochondrial genome in cardiac function without the confounding effects of obesity or hypertension found in other models of diabetes. Echocardiographic analysis of 12-week-old animals showed no abnormalities, but at 12 months of age the T2DN(mtFHH) showed left ventricular remodeling that was verified by histology. Decreased complex I and complex IV but not complex II activity within the electron transport chain was found only in T2DN(mtFHH), which was not explained by differences in protein content. Decreased cardiac ATP levels in T2DN(mtFHH) were in agreement with a lower ATP synthetic capacity by isolated mitochondria. Together, our data provide experimental evidence that mtDNA sequence variations have an additional role in energetic heart deficiency. The mitochondrial DNA background may explain the increased susceptibility of certain T2DM patients to develop myocardial dysfunction.

Abstract 2101: Differential mtDNA sequence variants in primary tissues of colorectal adeno-polyps

Abstract Introduction: Increasing evidence suggest that mitochondrial alterations involved in cellular signal pathways have been associated with tumorigenesis. Differentially diagnosing progressive stages of colorectal adenomatous polyps is important for therapeutic intervention and surveillance. We hypothesized that Mitochondrial DNA (mtDNA) variants in colorectal adenomatous polyps are stage-specific genetic changes. We aimed to identify the genetic mtDNA mutations present in the early stages of colorectal cancer. Methods: MtDNA sequence variants among the different types of colorectal adenomatous polyps: Tubular, Tubulovillous and Villous adenomatous were analyzed from sixty-four tissue samples (33 tumor 31 matched surrounding normal tissue (NST)) with patients mean age 57.1±7. Two mtDNA regions were screened from each sample with two primer pairs spanning 8282-to-10107 and 11673-to-13950bp comprised of the MT-NC7, MT-TK, MT-ND3, ATPase 6, ATPase 8, COX III, ND3, ND4L, ND4 and ND5 genes. The presence of polymorphisms and other sequence variants of mtDNA were also evaluated using the high-resolution restriction endonucleases and PCR based sequencing. Results: Forty-two variants were observed of which 18 of 42 (42%) were not previously reported in the MITODAT reference database. The distribution of observed mutations included, 31% (13/42) Tubular, 52% (22/42) Tubulovillous, 45% (19/42) Villous, 45% (19/42) colorectal cancer (including FAP and JVP). Notably, unreported germline variant, G8573A, in the ATPase 8 gene region was found in 100% tubulovillous adenomas, but not any other samples. A heteroplasmic variant A11873G, in the MTND4 gene was detected in 67% tubular, 78% tubulovillous, 71% villous and 38% cancer subtypes. Given that mutations in ATPase 8 genes inhibits the production of ATP from ADP, and mutations in MTND4 genes prevent the normal interactions of complex I with ubiquinone, affecting the generation of ATP, these observed variants may influence the early stages of colorectal tumor. Conclusion: Therefore, our findings suggest that certain mtDNA sequence variants may contribute as a framework for further differentiation studies of stages of colorectal adeno-polyps. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2101. doi:1538-7445.AM2012-2101

Species-level phylogeny of ‘Satan’s perches’ based on discordant gene trees (Teleostei: Cichlidae: Satanoperca Günther 1862)

Neotropical rivers are home to the largest assemblage of freshwater fishes, but little is known about the phylogeny of these fishes at the species level using multi-locus molecular markers. Here, we present a phylogeny for all known species of the genus Satanoperca, a widespread group of Neotropical cichlid fishes, based on analysis of six unlinked genetic loci. To test nominal and proposed species limits for this group, we surveyed mtDNA sequence variation among 320 individuals representing all know species. Most nominal species were supported by this approach but we determined that populations in the Xingu, Tapajós, and Araguaia+Paraná Rivers are likely undescribed species, while S. jurupari and S. mapiritensis did not show clear genetic distinction. To infer a phylogeny of these putative species, we conducted maximum likelihood and Bayesian non-clock and relaxed clock analyses of concatenated data from three genes (one mitochondrial, two nuclear). We also used a multi-species coalescent model to estimate a species tree from six unlinked loci (one mitochondrial, five nuclear). The topologies obtained were congruent with other results, but showed only minimal to moderate support for some nodes, suggesting that more loci will be needed to satisfactorily estimate the distribution of coalescent histories within Satanoperca. We determined that this variation results from topological discordance among separate gene trees, likely due to differential sorting of ancestral polymorphisms.

Ovine mitochondrial DNA sequence variation and its association with production and reproduction traits within an Afec-Assaf flock1

Polymorphisms in mitochondrial DNA (mtDNA) protein- and tRNA-coding genes were shown to be associated with various diseases in humans as well as with production and reproduction traits in livestock. Alignment of full length mitochondria sequences from the 5 known ovine haplogroups: HA (n = 3), HB (n = 5), HC (n = 3), HD (n = 2), and HE (n = 2; GenBank accession nos. HE577847-50 and 11 published complete ovine mitochondria sequences) revealed sequence variation in 10 out of the 13 protein coding mtDNA sequences. Twenty-six of the 245 variable sites found in the protein coding sequences represent non-synonymous mutations. Sequence variation was observed also in 8 out of the 22 tRNA mtDNA sequences. On the basis of the mtDNA control region and cytochrome b partial sequences along with information on maternal lineages within an Afec-Assaf flock, 1,126 Afec-Assaf ewes were assigned to mitochondrial haplogroups HA, HB, and HC, with frequencies of 0.43, 0.43, and 0.14, respectively. Analysis of birth weight and growth rate records of lamb (n = 1286) and productivity from 4,993 lambing records revealed no association between mitochondrial haplogroup affiliation and female longevity, lambs perinatal survival rate, birth weight, and daily growth rate of lambs up to 150 d that averaged 1,664 d, 88.3%, 4.5 kg, and 320 g/d, respectively. However, significant (P < 0.0001) differences among the haplogroups were found for prolificacy of ewes, with prolificacies (mean ± SE) of 2.14 ± 0.04, 2.25 ± 0.04, and 2.30 ± 0.06 lamb born/ewe lambing for the HA, HB, and the HC haplogroups, respectively. Our results highlight the ovine mitogenome genetic variation in protein- and tRNA coding genes and suggest that sequence variation in ovine mtDNA is associated with variation in ewe prolificacy.

Watershed boundaries and geographic isolation: patterns of diversification in cutthroat trout from western North America

BackgroundFor wide-ranging species, intraspecific variation can occur as a result of reproductive isolation from local adaptive differences or from physical barriers to movement. Cutthroat trout (Oncorhynchus clarkii), a widely distributed fish species from North America, has been divided into numerous putative subspecies largely based on its isolation in different watersheds. In this study, we examined mtDNA sequence variation of cutthroat trout to determine the major phylogenetic lineages of this polytypic species. We use these data as a means of testing whether geographic isolation by watershed boundaries can be a primary factor organizing intraspecific diversification.ResultsWe collected cutthroat trout from locations spanning almost the entire geographic range of this species and included samples from all major subspecies of cutthroat trout. Based on our analyses, we reveal eight major lineages of cutthroat trout, six of which correspond to subspecific taxonomy commonly used to describe intraspecific variation in this species. The Bonneville cutthroat trout (O. c. utah) and Yellowstone cutthroat trout (O. c. bouvieri) did not form separate monophyletic lineages, but instead formed an intermixed clade. We also document the geographic distribution of a Great Basin lineage of cutthroat trout; a group typically defined as Bonneville cutthroat trout, but it appears more closely related to the Colorado River lineage of cutthroat trout.ConclusionOur study indicates that watershed boundaries can be an organizing factor isolating genetic diversity in fishes; however, historical connections between watersheds can also influence the template of isolation. Widely distributed species, like cutthroat trout, offer an opportunity to assess where historic watershed connections may have existed, and help explain the current distribution of biological diversity across a landscape.

MtDNA and nuclear data reveal patterns of low genetic differentiation for the isopods &lt;i&gt;Stenosoma lancifer and Stenosoma acuminatum&lt;/i&gt;, with low dispersal ability along the northeast Atlantic coast

Evidence for a general lack of genetic differentiation of intertidal invertebrate assemblages in the North Atlantic, based on mtDNA sequence variation, has been interpreted as resulting from recent colonization following the Last Glacial Maximum. In the present study, the phylogeographic patterns of one nuclear and one mtDNA gene fragments of two isopods, Stenosoma lancifer (Miers, 1881) and Stenosoma acuminatum Leach, 1814, from the northeast Atlantic were investigated. These organisms have direct development, which makes them poor dispersers, and are therefore expected to maintain signatures of past historical events in their genomes. Lack of genetic structure, significant deviations from neutrality and star-like haplotype networks have been observed for both mtDNA and nuclear markers of S. lancifer , as well as for the mtDNA of S. acuminatum . No sequence variation was observed for the nuclear gene fragment of S. acuminatum . These results suggest a scenario of recent colonization and demographic expansion and/or high population connectivity driven by ocean currents and sporadic long-distance dispersal through rafting.

Genetic composition of green turtle feeding grounds in coastal waters of Argentina based on mitochondrial DNA

The green turtle, Chelonia mydas, like other species of marine turtles, shows great migratory displacement between its nesting and feeding grounds. In an attempt to characterize the southernmost feeding grounds of this species, mtDNA sequence variation of green turtle aggregations in Argentinean waters was studied to elucidate genetic variation and infer possible origins. The goal of the present study is contemplated within the main purpose of the PRICTMA (Regional Program for Sea Turtle Research in Conservation of Argentina) and the Network ASO-Tortugas (Red Atlántico Sur Occidental-Tortugas) which are dedicated to promoting conservation studies in marine turtles in the region. A 486-bp fragment of the mitochondrial DNA control region was sequenced from 93 samples of incidentally caught juveniles from 2004 to 2007, revealing 9 haplotypes. Nucleotide and haplotype diversity were similar to those detected in other Brazilian feeding grounds (Ubatuba and Atol das Rocas/Fernando de Noronha). Analysis of molecular variance (AMOVA) indicated significant genetic differentiation among 9 western Atlantic feeding grounds for which data is currently available, suggesting variable contributions from different nesting colonies (F ST = 0.29, P < 10 − 4 ; Φ ST = 0.55, P < 10 − 4 ). Mitochondrial DNA haplotype distributions revealed significant heterogeneity among feeding grounds ( Χ 2: 804.84, P < 10 − 4 ). A pairwise analysis revealed that most western Atlantic feeding grounds are genetically differentiated. The weighted and unweighted mixed stock analyses suggests that green turtles at Argentinean feeding grounds originate mainly in the Ascension Island rookery, with less contribution from rookeries in Suriname, Aves Island and Trindade Island. The present results improve our knowledge of the population structure and migration patterns of the Atlantic green turtle, and inform conservation measures on feeding grounds, which may be thousands of kilometers away from the nesting colonies. This information is required to further government efforts for this endangered species.

Phylogeography of the Rufous-tailed Hummingbird (Amazilia tzacatl)

Abstract. The Rufous-tailed Hummingbird (Amazilia tzacatl) is a common resident of the neotropical lowlands of Middle America and northern South America. The Escudo Hummingbird (A. t. handleyi), the most distinctive of the five subspecies of A. tzacatl, is endemic to Isla Escudo in Caribbean western Panama. Mitochondrial DNA (mtDNA) sequence variation from across most of the species' range showed five well-defined but shallow clades (maximum uncorrected distance 2.4%) that only partially agreed with subspecific taxonomy. A widespread Middle American clade ranges from southeastern Mexico to central Caribbean Panama and includes birds collected on the Bocas del Toro archipelago. The Escudo Hummingbird fell within this clade and was slightly differentiated (two unique substitutions; uncorrected distance ∼0.2–0.5%). Two additional clades occur in the Pacific regions of southern Middle America. A fourth clade is endemic to eastern Panama (eastern Panama and Darien provinces); a fifth is found in northwestern S...

Shape and sound reveal genetic cohesion not speciation in the New Zealand orthopteran, Hemiandrus pallitarsis, despite high mitochondrial DNA divergence

Levels of neutral mitochondrial (mt)DNA sequence diversity play a prominent role in alpha taxonomy, with divergence thresholds of approximately 3% widely being accepted as indicative of species differences. However, a number of studies of New Zealand invertebrates conclude that intraspecific mtDNA divergences are commonly much higher. We investigated the diversity and distribution of mitochondrial cytochrome oxidase I DNA sequences from populations of the New Zealand ground weta Hemiandrus pallitarsis with respect to variation among ten morphological characters and analysis of acoustic signalling associated with mate recognition. We looked for correlation between neutral mtDNA sequence variation and potential indicators of species differences. Despite high genetic distances (> 8.0% uncorrected) among mtDNA haplotypes in this species, morphological and male precopulation signals refute a hypothesis that multiple species exist. Other possible explanations for high genetic diversity, including accidental sampling of nuclear paralogues and elevated substitution rate, are not supported, whereas there is evidence for stable population size through time. We conclude that generalizations about genetic diversity and species status are overly simplistic. In some circumstances, notably southern hemisphere invertebrate taxa, species cohesion appears to have been retained throughout the Pleistocene, indicating the persistence of a relatively high population size. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105, 169‐186. ADDITIONAL KEYWORDS: DNA barcoding ‐ genetic diversity ‐ insect signalling ‐ phylogeography ‐ Pliocene ‐ population size ‐ speciation.

The effects of mitochondrial genotype on hypoxic survival and gene expression in a hybrid population of the killifish, Fundulus heteroclitus

The physiological link between oxygen availability and mitochondrial function is well established. However, whether or not fitness variation is associated with mitochondrial genotypes in the field remains a contested topic in evolutionary biology. In this study, we draw on a population of the teleost fish, Fundulus heteroclitus, where functionally distinct subspecies hybridize, likely as a result of past glacial events. We had two specific aims: (i) to determine the effect of mtDNA genotype on survivorship of male and female fish under hypoxic stress and (ii) to determine the effect of hypoxic stress, sex and mtDNA genotype on gene expression. We found an unexpected and highly significant effect of sex on survivorship under hypoxic conditions, but no significant effect of mtDNA genotype. Gene expression analyses revealed hundreds of transcripts differentially regulated by sex and hypoxia. Mitochondrial transcripts and other predicted pathways were among those influenced by hypoxic stress, and a transcript corresponding to the mtDNA control region was the most highly suppressed transcript under the conditions of hypoxia. An RT-PCR experiment on the control region was consistent with microarray results. Effects of mtDNA sequence variation on genome expression were limited; however, a potentially important epistasis between mtDNA sequence and expression of a nuclear-encoded mitochondrial translation protein was discovered. Overall, these results confirm that mitochondrial regulation is a major component of hypoxia tolerance and further suggest that purifying selection has been the predominant selective force on mitochondrial genomes in these two subspecies.

One variable species or multiple cryptic? Mitochondrial phylogeny of Central and North American Chlosyne lacinia (Lepidoptera: Nymphalidae)

Recent efforts to catalogue global biodiversity using genetic techniques have uncovered a number of "cryptic" species within morphologically similar populations that had previously been identified as single species. Chlosyne lacinia (Lepidoptera: Nymphalidae), with a range extending from the Southwest U.S. to South America, is one of the most phenotypically variable and broadly distributed butterfly species in the New World. We sampled populations of C. lacinia in two temperate locations (California and Arizona) and one tropical location (El Salvador) to determine if cryptic species were present at this scale (temperate vs. tropical). We examined mtDNA sequence variation in COI, COII, the intervening tRNA (Leucine-2), 16S, 12S and an additional intervening tRNA (Valine), accounting for approximately 20% of the mitochondrial genome (3479 bp). Among all C. lacinia individuals, sequence divergence did not exceed 0.0084 compared to a 0.06 estimated divergence between C. lacinia and congener C. leanira. We also found subclade structure which did not clearly correspond to geography or subspecific designation. Though the mitochondrial phylogeny suggests a complex evolutionary history and biogeography, we demonstrate that one C. lacinia species is distributed throughout North and Central America spanning a diverse set of temperate and tropical habitats.

Secondary contact in the Sea of Japan: the case of the Careproctus rastrinus species complex (Liparidae)

The Careproctus rastrinus species complex, widely known from the North Pacific, has been revealed recently to include nine genetically divergent groups on the basis of mitochondrial DNA (mtDNA) sequence variations. Herein we describe an AFLP analysis that focuses on three closely related groups in order to clarify the evolutionary history of the species complex in the Sea of Japan and off the Pacific coast of Japan. A principal coordinate analysis indicated the absence of nuclear divergence in two groups defined by mtDNA variations in the Sea of Japan, whereas another group from the Pacific coast of northern Japan was clearly distinct. This suggests extensive gene flow between two groups in the Sea of Japan as a result of secondary contact.

Mitochondrial Insertion–Deletion Polymorphism: Role in Disease Pathology

Mitochondrial DNA (mtDNA) sequence variations are associated with a number of human diseases. The 9-bp repeat sequence, CCCCCTCTA, in the intergenic region of MTCO2 and MTTK genes of the mtDNA has been extensively used in phylogenic studies. The sequence has been reported to be polymorphic in south-east Asians in isolated cases of mt diseases. This is the first systemic study identifying the role of insertion-deletion polymorphism in human disease. A total of 241 patients including those with cardiomyopathy, ataxias, and idiopathic neurological disorders along with 100 controls were screened; 2.9% of patients showed a single repeat (deletion) and 4.14% had three repeats (insertion), whereas all the controls had two repeats (normal). This indicates that the 9-bp insertion-deletion repeat polymorphism plays a role in disease pathology, affecting the expression of the downstream genes of mtDNA and altering ATP generation.

On the species identities of a complex Liolaemus fauna from the Altiplano and Atacama Desert: insights on Liolaemus stolzmanni, L. reichei, L. jamesi pachecoi, and L. poconchilensis (Squamata: Liolaemidae)

The South American lizard genus Liolaemus has undergone a complex adaptive radiation that has resulted in the evolution of more than 200 species widely spread in an extraordinary diversity of environments, and forming a complex array of assemblages. This evolutionary complexity has puzzled systematists and taxonomists since the first species were described more than 150 years ago. Within this lineage, the Andean Liolaemus faunas have proven to be a major challenge for herpetologists. Therefore, intense research is needed in this area to clarify long-standing problems. After more than a century of taxonomic confusion, the identity of Liolaemus stolzmanni (Steindachner, 1891) is here restored as the name that must be applied to the lizards widely known as Phrynosaura (= Liolaemus) reichei Werner, 1907 from the low to midelevation deserts of Tarapacá, Chile. Since 1966, the name L. stolzmanni has been erroneously assigned to populations of Liolaemus from the high Andes of the Chile-Bolivia borderlands which, according to observations presented in this study, correspond to Liolaemus pachecoi Laurent, 1995. A lectotype and allotype for L. stolzmanni are designated and the type locality for L. stolzmanni (= L. reichei) is emended to “Deserts of Iquique, Tarapacá Region, Chile”. Furthermore, the recognition of L. pachecoi as a species distinct from L. jamesi is supported by mtDNA sequence divergence data despite the inconclusive meristic and morphometric data. In summary, I conclude that (i) the Chilean L. reichei is a synonym of L. stolzmanni, and hence, that L. stolzmanni is a species endemic to Chile, not an element of the fauna of present-day Peru and that (ii) the Chilean Altiplano populations currently recognized as L. stolzmanni are L. pachecoi, a species hitherto known only from Bolivia. Also, I report the first confirmed specimens of L. poconchilensis from Peru, a species previously known only from Chile and confused with L. reichei.

Detection of Somatic Mutations and Germline Polymorphisms in Mitochondrial DNA of Uterine Fibroids Patients

To identify the role of mitochondrial DNA (mtDNA) mutations in uterine fibroids patients, genomic DNA isolated from paired myometrium and fibroid tissues was screened for mutations. The present study represents the first investigation to report that 10.4% of uterine fibroids cases had either mtDNA mutations or polymorphisms or both. Among the 14 mitochondrial sequence variants identified, seven are somatic mutations (A3327C, G3352A, G3376A, G3380A, G3421A, T15312G, and C15493G) and the remaining (G3316A, C3342A, C3442T, T10205A, A10188G, A10229C, and A10301T) are gene polymorphisms. Somatic mutations were both homo- and heteroplasmic in nature. Of the seven somatic mutations located in the MTND1 and MTCYB genes, five (71.42%) are nonsynonymous in nature, whereas four (57.14%) of the polymorphisms located in MTND1 and MTND3 genes are found to be nonsynonymous. Sequence variants such as G3380A, G3421A, T15312G, G3376A, and G3316A have been earlier described in different human pathologies, but the remaining are novel ones. Mitochondrial somatic mutations and polymorphisms may predispose women to an earlier onset of degenerative cellular processes, which impair oxidative phosphorylation capacity and thereby promote tumorigenesis in uterine smooth muscle cells. Detection of mtDNA sequence variations in fibroid patients raises the need for larger case-control studies to screen the whole mitochondrial genome and evaluate as a future diagnostic biomarker in fibroid patients.

Application of high‐resolution melting for genotyping bovine mitochondrial DNA

Recent studies have demonstrated that mitochondrial DNA (mtDNA) haplotype has a significant impact on the efficiency of bovine somatic cell nuclear transfer. Conventional methods for detecting mtDNA variations and haplotypes, such as restriction fragment length polymorphism (RFLP), temporal temperature gradient gel electrophoresis, dHPLC and sequencing, are labor intensive or expensive and have low sensitivity. High-resolution melting (HRM) analysis is a new technique for mutation detection and has the advantages of speed, cost, and accuracy. Here, we describe the genotyping of bovine mtDNA using HRM analysis. DNA samples containing mtDNA were extracted from 75 Holstein cows and subjected to rapid-cycle (<20 min) PCR of small amplicons (<120 bp) using specific primer sets. Capillaries containing the PCR products were then subjected to HRM analysis; data were acquired in 2 min and analyzed using the instrument's software. Five common bovine mtDNA single nucleotide polymorphisms were identified: 9602 G>A, 169 A>G, 166A>G with 173A>G, and 363C>G. These results agree with both sequencing and RFLP analysis. In addition, a very small amount of heteroplasmic variants (<5%) was sufficiently to be distinguished by HRM analysis that would be very useful to differentiate heteroplasmy vs. homoplasmy. HRM analysis thus provides a new approach to genotyping bovine mtDNA sequence variations and has many advantages over other methods, including speed of analysis, cost, and accuracy. We believe this will be a valuable technique for determining the efficiency of nuclear transfer in cloned embryos and for studying maternal effects on nuclear-cytoplasm interactions.

Introgression of mitochondrial DNA among Myodes voles: consequences for energetics?

BackgroundIntrogression of mitochondrial DNA (mtDNA) is among the most frequently described cases of reticulate evolution. The tendency of mtDNA to cross interspecific barriers is somewhat counter-intuitive considering the key function of enzymes that it encodes in the oxidative-phosphorylation process, which could give rise to hybrid dysfunction. How mtDNA reticulation affects the evolution of metabolic functions is, however, uncertain. Here we investigated how morpho-physiological traits vary in natural populations of a common rodent (the bank vole, Myodes glareolus) and whether this variation could be associated with mtDNA introgression. First, we confirmed that M. glareolus harbour mtDNA introgressed from M. rutilus by analyzing mtDNA (cytochrome b, 954 bp) and nuclear DNA (four markers; 2333 bp in total) sequence variation and reconstructing loci phylogenies among six natural populations in Finland. We then studied geographic variation in body size and basal metabolic rate (BMR) among the populations of M. glareolus and tested its relationship with mtDNA type.ResultsMyodes glareolus and its arctic neighbour, M. rutilus, are reciprocally monophyletic at the analyzed nuclear DNA loci. In contrast, the two northernmost populations of M. glareolus have a fixed mitotype that is shared with M. rutilus, likely due to introgressive hybridization. The analyses of phenotypic traits revealed that the body mass and whole-body, but not mass corrected, BMR are significantly reduced in M. glareolus females from northern Finland that also have the introgressed mitotype. Restricting the analysis to the single population where the mitotypes coexist, the association of mtDNA type with whole-body BMR remained but those with mass corrected BMR and body mass did not. Mitochondrial sequence variation in the introgressed haplotypes is compatible with demographic growth of the populations, but may also be a result of positive selection.ConclusionOur results show that the phenotypic traits vary markedly along the north-south axis of populations of M. glareolus. This variation may be related to adaptation to local environments and coincides with the gradient of genome reticulation between M. glareolus and M. rutilus, which was assessed by mtDNA introgression. Introgression of mtDNA may have affected morpho-physiological traits but do not show strong effects on either body mass or basal metabolic rate alone. We discuss the causes and biological meaning of our results and the means to clarify these questions in future research.

Mitochondrial DNA analysis of an immigrant basque population: Loss of diversity due to founder effects

The Basques have a well-documented history of migration and settlement in the Americas, and they often retain cultural identity across generations. Numerous genetic studies have been carried out on European Basques; thus, immigrant Basques are an ideal population for investigating the genetic consequences of a recent human migration event. We have sampled 53 unrelated individuals with Basque ancestry in Boise, Idaho and determined the mitochondrial DNA (mtDNA) sequence variation of the first and second hypervariable regions. Thirty-six mtDNA haplotypes were detected in our sample. We found evidence of genetic changes consistent with founder effects, which is compatible with the known history of migration. Compared with the European Basque population, the immigrant Basques are significantly different in terms of haplogroup frequency distribution and diversity. They have a lower measure of weighted intralineage mean pairwise diversity (WIMP) and greater genetic distance from other European populations. These data indicate that this immigrant Basque population has experienced a reduction in genetic diversity compared with the putative source population. However, this loss of diversity is not detectable using indices of demographic history such as Tajima's D and Fu's F. This study represents the first description of mtDNA diversity in an immigrant Basque population, and our findings indicate that founder effects accompanying this relatively recent migration event have shaped the genetic diversity of this population.

Assessing mitochondrial DNA nucleotide changes in spontaneous optic neuropathies

Purpose: The high mutation rate in the mitochondrial genome makes it difficult to be certain about mtDNA pathology, and yet we now recognize several primary and provisional Leber hereditary optic neuropathy (LHON) mutations (which are commonly pathologic) and a larger number of secondary LHON mutations (which are often associated with certain primary LHON mutations and may contribute to pathogenicity), haplogroup-specific mitochondrial DNA (mtDNA) sequence variants, and simple polymorphisms (which are not commonly pathologic).Conclusions: An enormous amount of information is now known about mitochondria, the apparent dependence of the optic nerve on mitochondria, various metabolic effects of primary LHON mutations, and certain ways in which these nucleotide changes might harm the optic nerve are discussed.

Germline Transmission of Mitochondrial DNA in the Mouse.

In mammals, mitochondria and mitochondrial DNA (mtDNA) are transmitted through the female germline. Mature oocytes contain nearly 200,000 copies of mtDNA, organized at 1-2 copies per organelle. Despite the high genome copy number, mtDNA sequence variants are observed to segregate rapidly between generations, and this has led to the concept of a genetic bottleneck for the transmission of mtDNA. Here, we demonstrate that a subgroup of replicating genomes in the early post-natal ovary is responsible for the rapid segregation of mtDNA and show that the rate of segregation of mtDNA can be accelerated when mtDNA copy number is further reduced in heteroplasmic germline-specific knockout mouse models, yet very extreme reductions in germ cell mtDNA content seem to cause female-specific infertility. Low copy number embryos can be fertilized and proceed through preimplantation development yet fail to develop normally after implantation. Tracking the developmental outcome of embryos containing a range of mtDNAs points to a developmental threshold of about 50,000 copies of mtDNA in the oocyte Thus, we advance the hypothesis that the large number of mitochondria and mtDNAs present in the oocyte represent a genetic mechanism to ensure their distribution to the gametes and somatic cells of the next generation. If true, mtDNA copy number may be the most important determinant of oocyte quality not because of the effects on oocyte metabolism, but because too few would result in a maldistribution in the embryo. (platform)