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Comparative mtDNA phylogeography of neotropical freshwater fishes: testing shared history to infer the evolutionary landscape of lower Central America.

Historical biogeography seeks to explain contemporary distributions of taxa in the context of intrinsic biological and extrinsic geological and climatic factors. To decipher the relative importance of biological characteristics vs. environmental conditions, it is necessary to ask whether groups of taxa with similar distributions share the same history of diversification. Because all of the taxa will have shared the same climatic and geological history, evidence of shared history across multiple species provides an estimate of the role of extrinsic factors in shaping contemporary biogeographic patterns. Similarly, differences in the records of evolutionary history across species will probably be signatures of biological differences. In this study, we focus on inferring the evolutionary history for geographical populations and closely related species representing three genera of primary freshwater fishes that are widely distributed in lower Central America (LCA) and northwestern Colombia. Analysis of mitochondrial gene trees provides the opportunity for robust tests of shared history across taxa. Moreover, because mtDNA permits inference of the temporal scale of diversification we can test hypotheses regarding the chronological development of the Isthmian corridor linking North and South America. We have focused attention on two issues. First, we show that many of the distinct populations of LCA fishes diverged in a relatively brief period of time thus limiting the phylogenetic signal available for tests of shared history. Second, our results provide reduced evidence of shared history when all drainages are included in the analysis because of inferred dispersion events that obscure the evolutionary history among drainage basins. When we restrict the analysis to areas that harbour endemic mitochondrial lineages, there is evidence of shared history across taxa. We hypothesize that there were two to three distinct waves of invasion into LCA from putative source populations in northwestern Colombia. The first probably happened in the late Miocene, prior to the final emergence of the Isthmus in the mid-Pliocene; the second was probably coincident with the rise of the Isthmus in the mid-Pliocene, and the third event occurred more recently, perhaps in the Pleistocene. In each case the geographical scale of the dispersion of lineages was progressively more limited, a pattern we attribute to the continuing development of the landscape due to orogeny and the consequent increase in the insularization of drainage basins. Thus, the fisheye view of LCA suggests a complex biogeographic history of overlaid cycles of colonization, diversification, sorting and extinction of lineages.

ATP Synthetase Complexes↗

Molecular population genetics of the red kangaroo (Macropus rufus): mtDNA variation.

The genetic population structure of a large, wide-ranging marsupial, the red kangaroo (Macropus rufus) was assessed using sequence and haplotype frequency data of mitochondrial DNA (mtDNA) from locations across the species range in Australia. Results from sequence data revealed extensive haplotype diversity within the red kangaroo (32/34 sequences were unique). Sequence diversity was distributed within rather than between geographical regions across the species range. Genetic connectivity across the range of the species has therefore been maintained over the long term. On a smaller within-region scale, significant genetic structuring was evident from heterogeneity of haplotype frequencies amongst sampling sites. The geographical scale of panmictic populations differed across the continent with more restricted genetic populations occurring in areas with greater topographic and habitat complexity. We propose that these differences in area of genetic populations are the result of population responses to limiting ecological factors during drought.

Animals↗

Haplotype (mtDNA) diversity of brown trout Salmo trutta in tributaries of the Austrian Danube: massive introgression of Atlantic basin fish--by man or nature?

Mitochondrial haplotype diversity in 27 populations of brown trout, Salmo trutta L., in Austria was investigated by sequencing the 5' end of the mitochondrial DNA (mtDNA) control region. Although all populations are within the Danube drainage, 44% of all individuals carried Atlantic basin haplotypes. It is argued that the presence of these haplotypes in Austria primarily reflects introgression stemming from the stocking of hatchery-reared fish. However, several lines of evidence suggest that some natural colonization from Atlantic lineages may have contributed to the present haplotype diversity. Nonetheless, the more diverse Danubian clade is represented by regionally distinct haplotype diversity that should be protected from the continued introduction of domesticated strains of exogenous fish

Animals↗

MtDNA mutations associated with sideroblastic anaemia cause a defect of mitochondrial cytochrome c oxidase.

We have recently described heteroplasmic mutations of mitochondrial DNA in patients suffering from sideroblastic anaemia. The mutations change conserved residues 1280 and M273 in subunit I of cytochrome oxidase, the terminal enzyme of the mitochondrial respiratory chain. As a step towards elucidating the pathogenic mechanism, we studied the biochemical consequences of the mutations by transferring mtDNA from these patients' platelets into a permanent human cell line lacking a mitochondrial genome. Mutation-induced changes of the enzyme and the energy metabolism of the cells were characterised in the transmitochondrial cell lines. One of the mutations resulted in a decreased cellular concentration of the enzyme and a corresponding decrease in activity. The second mutation changed the structure around the binuclear centre and forced the cells to rely more strongly on glycolysis.

Anemia, Sideroblastic↗

Inferring the most likely geographical origin of mtDNA sequence profiles.

In a number of practical cases it is important to determine the likely geographical origin of an individual or a biological sample. A dead body, old bones or a sample of semen may be available. Information on where the sample might come from can assist investigation or research. The first part of this paper is independent of specific data structure. We formulate the problem as a classification problem. Bayes' theorem allows different sources of information or data to be reconciled conveniently. The main part of the paper involves high dimensional data for which simple, standard methods are not likely to work properly. Mitochondrial DNA (mtDNA) data is a typical example of such data. We propose a procedure involving essentially two steps. First, principal component analysis is used to reduce the dimension of the data. Next, quadratic discriminant analysis performs the actual classification. A cross validation procedure is implemented to select the optimal number of principal components. The importance of using separate data sets for model fitting and testing is emphasized. This method distinguishes well between individuals with a self reported European (Icelandic or German) origin and SE Africans. In this case the error rate is 2.0%.

Africa↗

mtDNA from fossils reveals a radiation of Hawaiian geese recently derived from the Canada goose (Brantacanadensis).

Phylogenetic analysis of 1.35 kb of mtDNA sequence from fossils revealed a previously unknown radiation of Hawaiian geese, of which only one representative remains alive (the endangered Hawaiian goose or nene, Branta sandvicensis). This radiation is nested phylogenetically within a living species, the Canada goose (Branta canadensis) and is related most closely to the large-bodied lineage within that species. The barnacle goose (Branta leucopsis) is also nested within the Canada goose species and is related most closely to the small-bodied lineage of Canada geese. The peripheral isolation of the barnacle goose in the Palearctic apparently allowed the evolution of its distinctive plumage pattern, whereas the two Nearctic lineages of Canada geese share a primitive plumage pattern. The Hawaiian lineage of Canada geese diverged more dramatically, splitting into at least three species that differ in body size, body proportions, and flight ability. One fossil species, limited to the island of Hawaii, was related closely to the nene but was over four times larger, flightless, heavy-bodied and had a much more robust cranium. Application of a rate calibration to levels of DNA divergence suggests that this species evolved on the island of Hawaii in less than 500,000 years. This date is consistent with the potassium/argon-based age of the island of Hawaii of 430,000-500,000 years. The giant Hawaii goose resembles the moa-nalos, a group of massive, extinct, flightless ducks that lived on older Hawaiian Islands and thus is an example of convergent evolution of similar morphologies in island ecosystems.

Animals↗

Organization of Achlya mtDNA: a population with two orientations and a large inverted repeat containing the rRNA genes.

We have investigated mtDNA organization in the oömycetous water mold; Achlya, and report here that this primitive organism contains a circular mitochondrial genome of 49.8 kilobase pairs. Extensive restriction endonuclease analysis indicates that a significant portion of the genome is present as an inverted repeat. Of 52 restriction sites for 14 enzymes thus far mapped, 28 sites cluster in two 9.6-kilobase-pair regions; within these regions, the sequence of sites is inverted but the spacing between analogous sites is identical. The repeat arms have a maximum length of 12.1 kilobase pairs and are separated by 4.6-8.4 and 21.0-22.3 kilobase pairs of unique sequences. Transfer hybridization experiments show that genes for both the large and the small rRNAs are contained within each repeat. Restriction endonuclease analysis shows that the unique regions between the inverted repeats are present in both possible orientations with respect to each other and in approximately equal proportions. These orientational, or "flip-flop," isomers of the unique regions are postulated to occur by intramolecular homologous recombination between the repeated regions.

Base Sequence↗

Identification of the polypeptides encoded in the ATPase 6 gene and in the unassigned reading frames 1 and 3 of human mtDNA.

Antibodies prepared against chemically synthesized peptides predicted from the DNA sequence have been used to identify the polypeptides encoded in the ATPase 6 gene and in unidentified reading frames (URFs) 1 and 3 of human mtDNA. In particular, antibodies directed against the COOH-terminal nonapeptide of the putative polypeptide encoded in the ATPase 6 reading frame immunoprecipitated specifically component 17 of the HeLa cell mitochondrial translation products, the reaction being inhibited by the specific peptide. Similarly, antibodies directed against the COOH-terminal undecapeptide of the putative URF1 product or against the COOH-terminal heptapeptide of the presumptive URF3 product were effective in immunoprecipitating specifically component 12 or, respectively, component 24 of the mitochondrial translation products. The sizes of proteins 17, 12, and 24, as estimated from their electrophoretic mobilities, are compatible with their being the products of the ATPase 6 gene, URF1, and URF3, respectively.

Adenosine Triphosphatases↗

Geographical structuring in the mtDNA of Italians.

Geographical patterns of mtDNA variation were studied in 12 Italian samples (1072 individuals) by two different spatial autocorrelation methods. Separate analyses of the frequencies of 12 restriction morphs show North-South clines, differences between Sardinia and the mainland populations, and the effects of isolation by distance. A recently developed autocorrelation statistic summarizing molecular similarity at all sites (AIDA; autocorrelation index for DNA analysis) confirms the presence of a clinical pattern; differences between random pairs of haplotypes tend to increase with their geographical distance. The partition of gene diversity, however, reveals that most variability occurs within populations, whereas differences between populations are minor (GST = 0.057). When the data from the 12 samples are pooled, two descriptors of genetic variability (number of polymorphic sites and average sequence difference between pairs of individuals) do not behave as expected under neutrality. The presence of clinal patterns, Tajima's tests, and a simulation experiment agree in suggesting that population sizes increased rapidly in Italy and Sicily but not necessarily so in Sardinia. The distribution of pairwise sequence differences in the Italian peninsula (excluding Sardinia) permits a tentative location of the demographic increase between 8000 and 20,500 years ago. These dates are consistent with archaeological estimates of two distinct expansion processes, occurring, respectively, in the Neolithic and after the last glacial maximum in the Paleolithic. Conversely, there is no genetic evidence that such processes have had a major impact on the Sardinian population.

Biological Evolution↗

Testing migration patterns and estimating founding population size in Polynesia by using human mtDNA sequences.

The hypervariable 1 region of human mtDNA shows markedly reduced variability in Polynesians, and this variability decreases from western to eastern Polynesia. Fifty-four sequences from New Zealand Maori show that the mitochondrial variability with just four haplotypes is the lowest of any sizeable human group studied and that the frequency of haplotypes is markedly skewed. The Maori sequences, combined with 268 published sequences from the Pacific, are consistent with a series of founder effects from small populations settling new island groups. The distributions of haplotypes were used to estimate the number of females in founding population of New Zealand Maori. The three-step simulation used a randomly selected founding population from eastern Polynesia, an expansionary phase in New Zealand, and finally the random selection of 54 haplotypes. The results are consistent with a founding population that includes approximately 70 women (between 50 and 100), and sensitivity analysis shows that this conclusion is robust to small changes in haplotype frequencies. This size is too large for models postulating a very small founding population of "castaways," but it is consistent with a general understanding of Maori oral history as well as the results of recent canoe voyages recreating early trans-oceanic voyages.

Base Sequence↗

Phylogeny of Darwin's finches as revealed by mtDNA sequences.

Darwin's finches comprise a group of passerine birds first collected by Charles Darwin during his visit to the Galápagos Archipelago. The group, a textbook example of adaptive radiation (the diversification of a founding population into an array of species differentially adapted to diverse environmental niches), encompasses 14 currently recognized species, of which 13 live on the Galápagos Islands and one on the Cocos Island in the Pacific Ocean. Although Darwin's finches have been studied extensively by morphologists, ecologists, and ethologists, their phylogenetic relationships remain uncertain. Here, sequences of two mtDNA segments, the cytochrome b and the control region, have been used to infer the evolutionary history of the group. The data reveal the Darwin's finches to be a monophyletic group with the warbler finch being the species closest to the founding stock, followed by the vegetarian finch, and then by two sister groups, the ground and the tree finches. The Cocos finch is related to the tree finches of the Galápagos Islands. The traditional classification of ground finches into six species and tree finches into five species is not reflected in the molecular data. In these two groups, ancestral polymorphisms have not, as yet, been sorted out among the cross-hybridizing species.

Animals↗

Lack of complex I activity in human cells carrying a mutation in MtDNA-encoded ND4 subunit is corrected by the Saccharomyces cerevisiae NADH-quinone oxidoreductase (NDI1) gene.

The gene for the single subunit, rotenone-insensitive, and flavone-sensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae (NDI1) can completely restore the NADH dehydrogenase activity in mutant human cells that lack the essential mitochondrial DNA (mtDNA)-encoded subunit ND4. In particular, the NDI1 gene was introduced into the nuclear genome of the human 143B.TK(-) cell line derivative C4T, which carries a homoplasmic frameshift mutation in the ND4 gene. Two transformants with a low or high level of expression of the exogenous gene were chosen for a detailed analysis. In these cells the corresponding protein is localized in mitochondria, its NADH-binding site faces the matrix compartment as in yeast mitochondria, and in perfect correlation with its abundance restores partially or fully NADH-dependent respiration that is rotenone-insensitive, flavone-sensitive, and antimycin A-sensitive. Thus the yeast enzyme has become coupled to the downstream portion of the human respiratory chain. Furthermore, the P:O ratio with malate/glutamate-dependent respiration in the transformants is approximately two-thirds of that of the wild-type 143B.TK(-) cells, as expected from the lack of proton pumping activity in the yeast enzyme. Finally, whereas the original mutant cell line C4T fails to grow in medium containing galactose instead of glucose, the high NDI1-expressing transformant has a fully restored capacity to grow in galactose medium. The present observations substantially expand the potential of the yeast NDI1 gene for the therapy of mitochondrial diseases involving complex I deficiency.

Binding Sites↗

Using novel phylogenetic methods to evaluate mammalian mtDNA, including amino acid-invariant sites-LogDet plus site stripping, to detect internal conflicts in the data, with special reference to the positions of hedgehog, armadillo, and elephant.

We look at the higher-order phylogeny of mammals, analyzing in detail the complete mtDNA sequences of more than 40 species. We test the support for several proposed superordinal relationships. To this end, we apply a number of recently programmed methods and approaches, plus better-established methods. New pairwise tests show highly significant evidence that amino acid frequencies are changing among nearly all the genomes studied when unvaried sites are ignored. LogDet amino acid distances, with modifications to take into account invariant sites, are combined with bootstrapping and the Neighbor Joining algorithm to account for these violations of standard models. To weight the more slowly evolving sites, we exclude the more rapidly evolving sites from the data by using "site stripping". This leads to changing optimal trees with nearly all methods. The bootstrap support for many hypotheses varies widely between methods, and few hypotheses can claim unanimous support from these data. Rather, we uncover good evidence that many of the earlier branching patterns in the placental subtree could be incorrect, including the placement of the root. The tRNA genes, for example, favor a split between the group hedgehog, rodents, and primates versus all other sequenced placentals. Such a grouping is not ruled out by the amino acid sequence data. A grouping of all rodents plus rabbit, the old Glires hypothesis, is also feasible with stripped amino acid data, and rodent monophyly is also common. The elephant sequence allows confident rejection of the older taxon Ferungulata (Simpson, 1945). In its place, the new taxa Scrotifera and Fereuungulata are defined. A new likelihood ratio test is used to detect differences between the optimal tree for tRNA versus that for amino acids. While not clearly significant as made, some results indicate the test is tending towards significance with more general models of evolution. Individual placement tests suggest alternative positions for hedgehog and elephant. Congruence arguments to support elephant and armadillo together are striking, suggesting a superordinal group composed of Xenarthra and African endemic mammals, which in turn may be near the root of the placental subtree. Thus, while casting doubt on some recent conclusions, the analyses are also unveiling some interesting new possibilities.

Animals↗

The effect on mitochondrial function of the tRNA Ser(UCN)/COI A7445G mtDNA point mutation associated with maternally-inherited sensorineural deafness.

An A to G point mutation at nucleotide position 7445 in the mitochondrial DNA genome is associated with maternally-inherited sensorineural deafness in two separate human pedigrees. To determine whether this point mutation [tRNA(SER)UCN)/COI A7445G] led to sensorineural deafness by affecting cellular energy metabolism we investigated the bioenergetic function of mitochondria in lymphoblastoid cultures established from these patients. Even though essentially all of the mitochondrial DNA in these cells contained the mutation at nucleotide position 7445, there was no effect on a number of mitochondrial bioenergetic functions (mitochondrial content, membrane potential in both intact and digitonin-permeabilised cells, cellular ATP/ADP ratios and respiratory enzyme activity) when compared with control cells. The implications of these findings for both the aetiology of the sensorineural deafness associated with the A7445G mtDNA mutation, and the role of bioenergetic defects in mitochondrial DNA diseases in general are discussed.

Adenosine Triphosphate↗

mtDNA history of the Cayapa Amerinds of Ecuador: detection of additional founding lineages for the Native American populations.

mtDNA variation in the Cayapa, an Ecuadorian Amerindian tribe belonging to the Chibcha-Paezan linguistic branch, was analyzed by use of hypervariable control regions I and II along with two linked regions undergoing insertion/deletion mutations. Three major maternal lineage clusters fit into the A, B, and C founding groups first described by Schurr and colleagues in 1990, whereas a fourth lineage, apparently unique to the Cayapa, has ambiguous affinity to known clusters. The time of divergence from a common maternal ancestor of the four lineage groups is of sufficient age that it indicates an origin in Asia and supports the hypothesis that the degree of variability carried by the Asian ancestral populations into the New World was rather high. Spatial autocorrelation analysis points out (a) statistically significant nonrandom distributions of the founding lineages in the Americas, because of north-south population movements that have occurred since the first Asian migrants spread through Beringia into the Americas, and (b) an unusual pattern associated with the D lineage cluster. The values of haplotype and nucleotide diversity that are displayed by the Cayapa appear to differ from those observed in other Chibchan populations but match those calculated for South American groups belonging to various linguistic stocks. These data, together with the results of phylogenetic analysis performed with the Amerinds of Central and South America, highlight the difficulty in the identification of clear coevolutionary patterns between linguistic and genetic relationships in particular human populations.

Base Sequence↗

Persistent heteroplasmy of a mutation in the human mtDNA control region: hypermutation as an apparent consequence of simple-repeat expansion/contraction.

In the genealogical and phylogenetic analyses that are reported here, we obtained evidence for an unusual pattern of mutation/reversion in the human mitochondrial genome. The cumulative results indicate that, when there is a T-->C polymorphism at nt 16189 and a C-->T substitution at nt 16192, there is an extremely high rate of reversion (hypermutation) at the latter site. The apparent reversion rate is sufficiently high that there is persistent heteroplasmy at nt 16192 in maternal lineages and at the phylogenetic level, a situation that is similar to that observed for the rapid expansion/contraction of simple repeats within the control region. This is the first specific instance in which the mutation frequency at one site in the D-loop is markedly influenced by the local sequence "context." The 16189 T-->C polymorphism lengthens a (C:G)n simple repeat, which then undergoes expansion and contraction, probably through replication slippage. This proclivity toward expansion/contraction is more pronounced when there is a C residue, rather than a T, at nt 16192. The high T-->C reversion frequency at nt 16192 apparently is the result of polymerase misincorporation or slippage during replication, the same mechanism that also causes the expansion/contraction of this simple-repeat sequence. In addition to the first analysis of this mitochondrial hypermutation process, these results also yield mechanistic insights into the expansion/contraction of simple-repeat sequences in mtDNA.

Base Sequence↗

Intragenic inversion of mtDNA: a new type of pathogenic mutation in a patient with mitochondrial myopathy.

We report an unusual molecular defect in the mitochondrially encoded ND1 subunit of NADH ubiquinone oxidoreductase (complex I) in a patient with mitochondrial myopathy and isolated complex I deficiency. The mutation is an inversion of seven nucleotides within the ND1 gene, which maintains the reading frame. The inversion, which alters three highly conserved amino acids in the polypeptide, was heteroplasmic in the patient's muscle but was not detectable in blood. This is the first report of a pathogenic inversion mutation in human mtDNA.

Adult↗

A novel homoplasmic mutation in mtDNA with a single evolutionary origin as a risk factor for cardiomyopathy.

To clarify the relationship between variation in mtDNA and the development of cardiomyopathy (CM), the complete sequences of mtDNAs of two brothers with dilated CM were compared with those of 181 patients who had CM and with those of 168 control subjects. Five patients with CM shared a novel homoplasmic point mutation (G12192A tRNA(His)), and all of them demonstrated the evolutionarily related D-loop sequence. The results suggest that this novel mutation originated from the same ancestor and that its presence strongly predisposes carriers to CM.

Cardiomyopathies↗