Mitochondrial Sequence Variation Research Articles

Phylogeography and conservation genetics of a distinct lineage of sunfish in the Cuatro Ciénegas valley of Mexico.

The valley of Cuatro Ciénegas, an aquatic oasis located in the Mexican Chihuahuan Desert, exhibits the highest level of endemism in North America and is a Mexican National Protected Area. However, little is known about the evolutionary distinctiveness of several vertebrate species present in the Cuatro Ciénegas valley. We conducted a phylogeographic study using mitochondrial haplotypes from the centrarchid fish Lepomis megalotis to determine if the populations found within the valley were evolutionarily distinct from populations outside the valley. We also examined if there was evidence of unique haplotypes of this sunfish within the valley. Genetic divergence of L. megalotis suggests populations within the valley are evolutionarily unique when compared to L. megalotis outside the valley. Significant mitochondrial sequence divergence was also discovered between L. megalotis populations on either side of the Sierra de San Marcos that bisects the valley. Our results reinforce previous studies that suggest the organisms occupying aquatic habitats not only within Cuatro Ciénegas but also in each of the two lobes of the valley generally deserve independent consideration during management decisions.

Mitochondrial sequence variation in African-American primary open-angle glaucoma patients.

Primary open-angle glaucoma (POAG) is a major cause of blindness and results from irreversible retinal ganglion cell damage and optic nerve degeneration. In the United States, POAG is most prevalent in African-Americans. Mitochondrial genetics and dysfunction have been implicated in POAG, and potentially pathogenic sequence variations, in particular novel transversional base substitutions, are reportedly common in mitochondrial genomes (mtDNA) from POAG patient blood. The purpose of this study was to ascertain the spectrum of sequence variation in mtDNA from African-American POAG patients and determine whether novel nonsynonymous, transversional or other potentially pathogenic sequence variations are observed more commonly in POAG cases than controls. mtDNA from African-American POAG cases (n = 22) and age-matched controls (n = 22) was analyzed by deep sequencing of a single 16,487 base pair PCR amplicon by Ion Torrent, and candidate novel variants were validated by Sanger sequencing. Sequence variants were classified and interpreted using the MITOMAP compendium of polymorphisms. 99.8% of the observed variations had been previously reported. The ratio of novel variants to POAG cases was 7-fold lower than a prior estimate. Novel mtDNA variants were present in 3 of 22 cases, novel nonsynonymous changes in 1 of 22 cases and novel transversions in 0 of 22 cases; these proportions are significantly lower (p<.0005, p<.0004, p<.0001) than estimated previously for POAG, and did not differ significantly from controls. Although it is possible that mitochondrial genetics play a role in African-Americans’ high susceptibility to POAG, it is unlikely that any mitochondrial respiratory dysfunction is due to an abnormally high incidence of novel mutations that can be detected in mtDNA from peripheral blood.

Mitochondrial D-loop sequence variation among Hucul horse

Genetic variation in the Czech Hucul horse population was analyzed using a sequence analysis of the D-loop region of mitochondrial DNA. One hundred and sixty-five Hucul horses were tested. Sequencing of the 700-base pairs fragment of the mitochondrial DNA D-loop region revealed 38 mutation sites representing 14 haplotypes, which were clustered into six haplogroups. The genetic information obtained from the mitochondrial DNA typing is of utmost importance for the future breed-conservation strategies. &amp;nbsp;

The evolutionary history of the order Antipatharia (Cnidaria: Anthozoa: Hexacorallia) as inferred from mitochondrial and nuclear DNA: implications for black coral taxonomy and systematics

Although black corals inhabit all the world's oceans, they have been relatively understudied as ∼185 of 247 species occur at depths > 50 m. Antipatharians have been included in several phylogenetic studies; however, sample sizes are small and taxonomic coverage minimal. Low levels of mitochondrial (mt) sequence divergence within Scleractinia and Octocorallia are assumed to apply to all anthozoans, although no formal study has been conducted on the order Antipatharia. To quantify genetic variation in the black coral mitogenome, we analysed DNA sequences of the two longest intergenic regions (IGRs) and cox3-cox1 for 26 of 41 genera, representing all families and subfamilies. We also quantified divergence at the intraspecific level using six mtIGRs and their flanking protein-coding genes and rRNA for 100+ colonies of Antipathes griggi. Utilizing sequence data from the two mtIGRs, cox3-cox1, as well as nuclear 18S and 28S, we constructed the first multi-locus phylogenies of the Antipatharia. Reconstructions revealed that species in the genus Stichopathes are split across two families, Sibopathes macrospina groups among North Atlantic Parantipathes (suggesting the actinopharynx and mesenteries were secondarily lost), and three families are polyphyletic. These and other results provide novel, independent insights into the evolutionary history of antipatharians and support placement of species into higher-level groupings based on microscopic skeletal features rather than gross colony morphology. An illustrated key to the seven currently recognized families is also provided. © 2013 The Linnean Society of London

A new Nototriton (Caudata: Plethodontidae) from Parque Nacional Montaña de Botaderos in northeastern Honduras.

The highlands of northeastern Honduras remain under-characterized in terms of biological diversity, as exemplified by the regularity of new amphibian and reptile taxa discoveries. Following the recent description of a new species of Nototriton from the Sierra de Agalta in northeastern Honduras, we report the discovery of a second new species of Nototriton from the nearby Parque Nacional Montaña de Botaderos. This new taxon, Nototriton mime sp. nov., is distinguished from other Nototriton by its distinctive pale brown dorsal coloration in adult males, relatively large nares, a relatively broad head, mitochondrial sequence divergence, and phylogenetic relationships, and is geographically isolated from other populations of Nototriton.

The Clinical and Audiologic Features of Hearing Loss Due to Mitochondrial Mutations

To characterize mitochondrial sequence variants present in a nationwide hereditary deafness DNA repository of samples from deaf subjects and to define the clinical presentation and audiometric characteristics of individuals with a mitochondrial sequence variant. Retrospective review of results for select mitochondrial mutations performed on DNA samples from subjects compiled from 1997 to 2009. National hereditary deafness DNA repository. Available samples from subjects in the repository were screened to identify those with mitochondrial sequence variants. Clinical data on the nature of mutation, type and severity of the hearing loss, and sex, age at diagnosis, family history of hearing loss, and ethnicity were analyzed. Eighty-six patients were identified with mitochondrial mutations or 3.5% of the subjects studied. Among those with mitochondrial mutations, 21 (24.4%) had the m.7445A>G substitution, 18 (20.9%) had the m.1555A>G substitution, 18 (20.9%) had the m.961T>G substitution, and 29 (33.7%) had a m.961delT+C(n) complex deletion. The majority of patients had bilateral severe to profound hearing loss. Fifty-three (62%) patients were female, and a family history of hearing loss was documented in 66 (76.7%) patients. The deafness was recognized prior to 3 years of age in 26 patients. Mitochondrial deafness in this sample was associated with a variety of genetic mutations and a wide spectrum of clinical presentations. Because of increased aminoglycoside susceptibility associated with some forms of mitochondrial deafness, matrilineal relatives may be at risk in those cases, highlighting the importance of making an accurate diagnosis prior to exposure.

Relationships of osmerid fishes (Osmeridae) of Russia: divergence of nucleotide sequences of mitochondrial and nuclear genes

Relationships of seven species of smelts (family Osmeridae) inhabiting Russian waters were analyzed on the basis of nucleotide sequence divergence of cytb, COI and intron 1 of rpS7 genes. Nuclear sequence divergence between the species within of the genera Osmerus, Mallotus and Hypomesus was 1.6–2.6, 2.9 and 6.6–11.8 %, respectively, and mitochondrial sequence divergence was 8.9–9.7, 3.9 and 15.1–18.3 %, respectively. The mtDNA divergence was 20.4 % between the genera Hypomesus and Mallotus, 18.47 % between Hypomesus and Osmerus, and 17.62 % between Mallotus and Osmerus. Nuclear DNA divergence was 11.58, 11.19, and 11.37 %, respectively. MP, ML and Bayesian analyses coupled with inclusion in analyses of GenBank-derived sequences of osmerid species that do not inhabit this region suggest that the lineage of the genus Mallotus was the first to separate from the common hypothetic ancestor of the smelts and is sister to the Osmerus–Hypomesus clade. The position of Hypomesus olidus is not resolved and points to the need for further research.

The influence of clan structure on the genetic variation in a single Ghanaian village

Socioeconomic and cultural factors are thought to have an important role in influencing human population genetic structure. To explain such population structure differences, most studies analyse genetic differences among widely dispersed human populations. In contrast, we have studied the genetic structure of an ethnic group occupying a single village in north-eastern Ghana. We found a markedly skewed male population substructure because of an almost complete lack of male gene flow among Bimoba clans in this village. We also observed a deep male substructure within one of the clans in this village. Among all males, we observed only three Y-single-nucleotide polymorphism (SNP) haplogroups: E1b1a*-M2, E1b1a7a*-U174 and E1b1a8a*-U209, P277, P278. In contrast to the marked Y-chromosomal substructure, mitochondrial DNA HVS-1 sequence variation and autosomal short-tandem repeats variation patterns indicate high genetic diversities and a virtually random female-mediated gene flow among clans. On the extreme micro-geographical scale of this single Bimoba village, correspondence between the Y-chromosome lineages and clan membership could be due to the combined effects of the strict patrilocal and patrilineal structure. If translated to larger geographic scales, our results would imply that the extent of variation in uniparentally inherited genetic markers, which are typically associated with historical migration on a continental scale, could equally likely be the result of many small and different cumulative effects of social factors such as clan membership that act at a local scale. Such local scale effects should therefore be considered in genetic studies, especially those that use uniparental markers, before making inferences about human history at large.

Maintenance of genetic variation and panmixia in the commercially exploited western rock lobster (Panulirus cygnus)

Marine species with high fecundities and mortalities in the early life stages can have low effective population sizes, making them vulnerable to declines in genetic diversity when they are commercially harvested. Here, we compare levels of microsatellite and mitochondrial sequence variation in the western rock lobster (Panulirus cygnus) over a 14-year period to test whether genetic variation is being maintained. Panulirus cygnus is a strong candidate for loss of genetic variation because it is a highly fecund species that is likely to experience high variance in reproductive success due to an extended larval planktonic stage. It also supports one of the largest and most economically important fisheries in Australia, with landings of between 8,000 and 14,500 tons (~70 % of the total legal-sized biomass) being harvested in some years. We found remarkably high levels of genetic variation in all samples and no evidence of a decline in genetic diversity over the time interval we studied. Furthermore, there was no evidence of a recent genetic bottleneck, and effective population size estimates based on single sample and temporal methods were infinitely large. Analysis of molecular variance indicated no significant population structure along 960 km of coastline or genetic differentiation among temporal samples. Our results support the view that P. cygnus is a single, panmictic population, and suggest genetic drift is not strong enough to reduce neutral genetic diversity in this species if current management practices and breeding stock sizes are maintained.

Phylogeographic pointers to conservation needs: South Africa's flagship dung beetle,Circellium bacchus

Circellium bacchus is South Africa's largest ball-rolling dung beetle and a habitat specialist of dense bush. It is also wingless, a rare phenomenon amongst large dung beetles and, unusual for the group, only females construct and bury brood balls. She cares for the single brood for 4–5 months, and lives for 3–5 years. The beetles currently occur in two separate populations in South Africa, one in the south-east and one consisting of at least eight fragmented sub-populations in the south-west. Here, we use both mitochondrial and nuclear DNA sequences to infer the evolutionary history of this species. The Eastern and Western populations are genetically separated by 14% mitochondrial sequence divergence, sharing only a single nuclear haplotype. Mitochondrial and nuclear data indicate that C. bacchus belongs to an ancient (Eocene) relict lineage and that the Eastern and Western populations appear to have been separated by Pliocene continental uplift and a relictual Pleistocene block of temperate forest. Subsequent Plio-Pleistocene climatic change caused further fragmentation of the Western population, now exacerbated by human-induced land transformation. The Eastern and Western populations are identifiable as two distinctly separate entities of possible species status, but with definite need for recognition as evolutionary significant units. The Western sub-populations are genetically significantly different enough to be defined and recognised as management units. The Eastern population is largely distributed in the Addo Elephant National Park where its persistence is currently secure, but the sub-populations of the Western lineage occur as fragments of various sizes in a matrix of agriculturally transformed landscape.

Loss of genetic variability in social spiders: genetic and phylogenetic consequences of population subdivision and inbreeding

The consequences of population subdivision and inbreeding have been studied in many organisms, particularly in plants. However, most studies focus on the short-term consequences, such as inbreeding depression. To investigate the consequences of both population fragmentation and inbreeding for genetic variability in the longer term, we here make use of a natural inbreeding experiment in spiders, where sociality and accompanying population subdivision and inbreeding have evolved repeatedly. We use mitochondrial and nuclear data to infer phylogenetic relationships among 170 individuals of Anelosimus spiders representing 23 species. We then compare relative mitochondrial and nuclear genetic variability of the inbred social species and their outbred relatives. We focus on four independently derived social species and four subsocial species, including two outbred–inbred sister species pairs. We find that social species have 50% reduced mitochondrial sequence divergence. As inbreeding is not expected to reduce genetic variability in the maternally inherited mitochondrial genome, this suggests the loss of variation due to strong population subdivision, founder effects, small effective population sizes (colonies as individuals) and lineage turnover. Social species have < 10% of the nuclear genetic variability of the outbred species, also suggesting the loss of genetic variability through founder effects and/or inbreeding. Inbred sociality hence may result in reduction in variability through various processes. Sociality in most Anelosimus species probably arose relatively recently (0.1–2 mya), with even the oldest social lineages having failed to diversify. This is consistent with the hypothesis that inbred spider sociality represents an evolutionary dead end. Heterosis underlies a species potential to respond to environmental change and/or disease. Inbreeding and loss of genetic variability may thus limit diversification in social Anelosimus lineages and similarly pose a threat to many wild populations subject to habitat fragmentation or reduced population sizes.

Mitochondrial sequence variation suggests extensive cryptic diversity within the Western Palearctic Daphnia longispina complex

We report on a discovery of six divergent lineages within the European Daphnia longispina complex from various localities in central to northeast Europe. The levels of divergence from well‐known species of the complex suggest that they represent as yet unrecognized distinct taxa. These newly recognized lineages always coexisted in syntopy with widespread species of the complex. Particularly rich in cryptic diversity (with four of the six lineages present) was the delta of the River Pechora in northern European Russia, a region not covered by an ice sheet during most of the last glacial period. We suggest that ice‐free regions of northeastern Europe may have been important refugia for planktonic species, and still are overlooked hot spots of diversity. Our findings confirm that the real diversity within widespread crustacean planktonic taxa is much higher than presently recognized. The potential presence of cryptic species should be considered in ecological studies.

Intraspecific variation in mitochondrial genome sequence, structure, and gene content in Silene vulgaris, an angiosperm with pervasive cytoplasmic male sterility

In angiosperms, mitochondrial-encoded genes can cause cytoplasmic male sterility (CMS), resulting in the coexistence of female and hermaphroditic individuals (gynodioecy). We compared four complete mitochondrial genomes from the gynodioecious species Silene vulgaris and found unprecedented amounts of intraspecific diversity for plant mitochondrial DNA (mtDNA). Remarkably, only about half of overall sequence content is shared between any pair of genomes. The four mtDNAs range in size from 361 to 429kb and differ in gene complement, with rpl5 and rps13 being intact in some genomes but absent or pseudogenized in others. The genomes exhibit essentially no conservation of synteny and are highly repetitive, with evidence of reciprocal recombination occurring even across short repeats (<250bp). Some mitochondrial genes exhibit atypically high degrees of nucleotide polymorphism, while others are invariant. The genomes also contain a variable number of small autonomously mapping chromosomes, which have only recently been identified in angiosperm mtDNA. Southern blot analysis of one of these chromosomes indicated a complex in vivo structure consisting of both monomeric circles and multimeric forms. We conclude that S.vulgaris harbors an unusually large degree of variation in mtDNA sequence and structure and discuss the extent to which this variation might be related to CMS.

AFLP markers resolve intra-specific relationships and infer genetic structure among lineages of the canyon treefrog, Hyla arenicolor

The canyon treefrog, Hyla arenicolor, is a wide-ranging hylid found from southwestern US into southern Mexico. Recent studies have shown this species to have a complex evolutionary history, with several phylogeographically distinct lineages, a probable cryptic species, and multiple episodes of mitochondrial introgression with the sister group, the H. eximia complex. We aimed to use genome wide AFLP markers to better resolve relationships within this group. As in other studies, our inferred phylogeny not only provides evidence for repeated mitochondrial introgression between H. arenicolor lineages and H. eximia/H. wrightorum, but it also affords more resolution within the main H. arenicolor clade than was previously achieved with sequence data. However, as with a previous study, the placement of a lineage of H. arenicolor whose distribution is centered in the Balsas Basin of Mexico remains poorly resolved, perhaps due to past hybridization with the H. eximia complex. Furthermore, the AFLP data set shows no differentiation among lineages from the Grand Canyon and Colorado Plateau despite their large mitochondrial sequence divergence. Finally, our results infer a well-supported sister relationship between this combined Colorado Plateau/Grand Canyon lineage and the Sonoran Desert lineage, a relationship that strongly contradicts conclusions drawn from the mtDNA evidence. Our study provides a basis for further behavioral and ecological speciation studies of this system and highlights the importance of multi-taxon (species) sampling in phylogenetic and phylogeographic studies.

Traits of Mitochondrial Deafness in a National Repository

Objective: 1) Characterize the mitochondrial sequence variants present in a national hereditary deafness DNA repository. 2) Define clinical presentation and audiometric characteristics of the various subgroups. Method: Retrospective record review of 86 patients with mitochondrial sequence variants compiled in a national hereditary deafness DNA repository from 1997-2008. Results: Of the 86 patients with mitochondrial sequence variants, 21 (24.4%) had the m. 7445A&gt;G mutation, 18 (20.9%) had the m.1555 A&gt;G, 18 (20.9%) had the m.961 T&gt;G mutation, and 29 (33.7%) had a different mutation at the m961 position, most of which (62%) were the m. 961delT+C(n) variant. The majority of patients had bilateral severe to profound hearing loss. Fifty-three (62%) patients were female and a family history of hearing loss was documented in 60 (69.7%) patients. Deafness was diagnosed before 3 years old in 26 patients. Conclusion: Mitochondrial deafness can be caused by a variety of genetic mutations with a wide spectrum of clinical presentations. Because of the increased aminoglycoside susceptibility in some forms, it is important to make an accurate diagnosis prior to exposure.

Extreme mitochondrial population subdivision in southern Appalachian paleoendemic spiders (Araneae: Hypochilidae: Hypochilus), with implications for species delimitation

A prior study of molecular phylogenetic relationships in southern Appalachian Hypochilus taxa revealed unusually high intraspecific mitochondrial sequence divergences, but was limited by small intraspecific sample sizes. A subsequent in-depth population genetic study focused on a single species (H. thorelli Marx 1888), revealing genetic patterns consistent with extremely limited female-based gene flow among rock-outcrop limited populations. Here we extend the study of mitochondrial population genetic structuring to four remaining Appalachian Hypochilus species. Genetic inferences are based on a sample of COI mitochondrial sequences generated for over 250 specimens from 85 sampled locations. This geographic sample comprehensively covers the geographic distributions of all described taxa. Phylogenetic, network-based, and genealogical sorting index analyses reveal ubiquitous genetic structuring in all Hypochilus taxa. A majority of sampled locations possess limited genetic variation, with site-specific haplotypes forming genealogically exclusive ''microclades'', consistent with limited female-based gene flow at the spatial scales sampled. At deeper phylogenetic levels, four of five described species are recovered as monophyletic on mitochondrial gene trees. Hypochilus pococki Platnick 1987 is recovered as paraphyletic, and is fragmented into five genetically divergent, allopatric phylogroups. These phylogroups, and multiple clades within one of the H. pococki phylogroups, are also recovered as distinct clusters in a generalized mixed Yule-coalescent (GMYC) analysis, suggesting the possibility of multiple cryptic species in the Appalachian fauna. However, a qualitative survey of male palpal variation fails to reveal morphological differences that distinguish these highly divergent genetic lineages. We suggest that a nuclear gene tree perspective is ultimately needed to resolve this contrast.

Variation in mitochondrial genome primary sequence among whole-genome-sequenced strains of Neurospora crassa

Eighteen classical mutant strains of Neurospora crassa were subject to whole genome sequence analysis and the mitochondrial genome is analyzed. Overall, the mitochondrial genomes of the classical mutant strains are 99.45 to 99.98 % identical to the reference genome. Two-thirds of the SNPs and three-fourths of indels identified in this analysis are shared among more than one strain. Most of the limited variability in mitochondrial genome sequence is neutral with regard to protein structure. Despite the fact that the mitochondrial genome is present in multiple copies per cell, many of the polymorphisms were homozygous within each strain. Conversely, some polymorphisms, especially those associated with large scale rearrangements are only present in a fraction of the reads covering each region. The impact of this variation is unknown and further studies will be necessary to ascertain if this level of polymorphism is common among fungi and whether it reflects the impact of ageing cultures.

Mitochondrial DNA sequence variation is associated with free-living activity energy expenditure in the elderly

The decline in activity energy expenditure underlies a range of age-associated pathological conditions, neuromuscular and neurological impairments, disability, and mortality. The majority (90%) of the energy needs of the human body are met by mitochondrial oxidative phosphorylation (OXPHOS). OXPHOS is dependent on the coordinated expression and interaction of genes encoded in the nuclear and mitochondrial genomes. We examined the role of mitochondrial genomic variation in free-living activity energy expenditure (AEE) and physical activity levels (PAL) by sequencing the entire (~16.5 kilobases) mtDNA from 138 Health, Aging, and Body Composition Study participants. Among the common mtDNA variants, the hypervariable region 2 m.185G>A variant was significantly associated with AEE (p=0.001) and PAL (p=0.0005) after adjustment for multiple comparisons. Several unique nonsynonymous variants were identified in the extremes of AEE with some occurring at highly conserved sites predicted to affect protein structure and function. Of interest is the p.T194M, CytB substitution in the lower extreme of AEE occurring at a residue in the Qi site of complex III. Among participants with low activity levels, the burden of singleton variants was 30% higher across the entire mtDNA and OXPHOS complex I when compared to those having moderate to high activity levels. A significant pooled variant association across the hypervariable 2 region was observed for AEE and PAL. These results suggest that mtDNA variation is associated with free-living AEE in older persons and may generate new hypotheses by which specific mtDNA complexes, genes, and variants may contribute to the maintenance of activity levels in late life.

The Origins of African Plasmodium vivax; Insights from Mitochondrial Genome Sequencing

Plasmodium vivax, the second most prevalent of the human malaria parasites, is estimated to affect 75 million people annually. It is very rare, however, in west and central Africa, due to the high prevalence of the Duffy negative phenotype in the human population. Due to its rarity in Africa, previous studies on the phylogeny of world-wide P. vivax have suffered from insufficient samples of African parasites. Here we compare the mitochondrial sequence diversity of parasites from Africa with those from other areas of the world, in order to investigate the origin of present-day African P. vivax. Mitochondrial genome sequencing revealed relatively little polymorphism within the African population compared to parasites from the rest of the world. This, combined with sequence similarity with parasites from India, suggests that the present day African P. vivax population in humans may have been introduced relatively recently from the Indian subcontinent. Haplotype network analysis also raises the possibility that parasites currently found in Africa and South America may be the closest extant relatives of the ancestors of the current world population. Lines of evidence are adduced that this ancestral population may be from an ancient stock of P. vivax in Africa.

Mitochondrial DNA diversity patterns in Pakistani buffalo

The Indian subcontinent is considered to be the likely centre of river buffalo domestication, based on population dynamics, archaeological evidence and genetic diversity. Recent studies on mitochondrial DNA diversity have drawn useful conclusions about the domestication history of Bubalus bubalis. The conclusions of these studies are, however, incomplete, unless samples can also be analysed from Pakistan, which contains the second largest buffalo population of the world. Here, we report the results of the first study on mitochondrial D-loop sequence diversity in five breeds of Pakistani buffalo. Analysis of sequence variations in 503-bp of the D-loop region of 123 animals revealed 52 haplotypes, including 40 singletons. Multidimensional display of breed pairwise F(ST) values revealed no strong clustering of breeds. Bayesian, maximum parsimony, neighbour joining and UPGMA trees revealed a topology consistent with domestication as well as subsequent introgression of multiple maternal lineages from the wild stocks. Reduced median network analysis provided evidence of population expansion from more than one set of haplotypes. The study also confirmed that Pakistani buffalo are of the river type. The observed mitochondrial D-loop sequence diversity suggests that Pakistani areas bordering India might have contributed to the initiation of domestication of the present-day river buffalo.