Mitochondrial DNA Sequence Polymorphisms Research Articles

Different but overlapping populations of Strongyloides stercoralis in dogs and humans-Dogs as a possible source for zoonotic strongyloidiasis.

Strongyloidiasis is a much-neglected soil born helminthiasis caused by the nematode Strongyloides stercoralis. Human derived S. stercoralis can be maintained in dogs in the laboratory and this parasite has been reported to also occur in dogs in the wild. Some authors have considered strongyloidiasis a zoonotic disease while others have argued that the two hosts carry host specialized populations of S. stercoralis and that dogs play a minor role, if any, as a reservoir for zoonotic S. stercoralis infections of humans. We isolated S. stercoralis from humans and their dogs in rural villages in northern Cambodia, a region with a high incidence of strongyloidiasis, and compared the worms derived from these two host species using nuclear and mitochondrial DNA sequence polymorphisms. We found that in dogs there exist two populations of S. stercoralis, which are clearly separated from each other genetically based on the nuclear 18S rDNA, the mitochondrial cox1 locus and whole genome sequence. One population, to which the majority of the worms belong, appears to be restricted to dogs. The other population is indistinguishable from the population of S. stercoralis isolated from humans. Consistent with earlier studies, we found multiple sequence variants of the hypervariable region I of the 18 S rDNA in S. stercoralis from humans. However, comparison of mitochondrial sequences and whole genome analysis suggest that these different 18S variants do not represent multiple genetically isolated subpopulations among the worms isolated from humans. We also investigated the mode of reproduction of the free-living generations of laboratory and wild isolates of S. stercoralis. Contrary to earlier literature on S. stercoralis but similar to other species of Strongyloides, we found clear evidence of sexual reproduction. Overall, our results show that dogs carry two populations, possibly different species of Strongyloides. One population appears to be dog specific but the other one is shared with humans. This argues for the strong potential of dogs as reservoirs for zoonotic transmission of S. stercoralis to humans and suggests that in order to reduce the exposure of humans to infective S. stercoralis larvae, dogs should be treated for the infection along with their owners.

Genetic diversity and matrilineal genetic signature of native Ethiopian donkeys (Equus asinus) inferred from mitochondrial DNA sequence polymorphism

We investigated mitochondrial DNA (mtDNA) sequence polymorphism of six morphologically diverse domestic donkey (Equus asinus) populations in Ethiopia. These populations include: Abyssinian (AB), Afar (AF), Hararghe (HR), Ogaden (OG), Omo (OM) and Sinnar (SI). Genetic relationships and other diversity parameters were inferred from 39 randomly selected mtDNA D-loop partial sequences, characterized by 29 polymorphic sites defining 19 distinct haplotypes. Moreover, haplotype and nucleotide diversity in Ethiopian donkey populations were 0.903±0.032 and 0.020±0.003, respectively. A network analysis produced moderate star-like patterns suggesting past population demographic and spatial expansion. Population subdivision estimates demonstrated that Sinnar donkeys were considerably divergent from the other donkey populations. To trace the matrilineal genetic origin of Ethiopian donkeys, we retrieved 221 previously published domestic donkeys’ mtDNA D-loop sequences from the GenBank (146 from Chinese and 75 from worldwide domestic donkeys). The haplogroup derived from the Ethiopian sources formed the center of the network from which most of the worldwide domestic donkey populations emerged. This suggests that Ethiopia could be one of the centers of diversities for domestic donkeys in the Horn of Africa. The present study also overrides some previous reports that claimed donkeys were solely an Egyptian domesticate.

Association between mitochondrial DNA variations and Alzheimer's disease in the ADNI cohort

Despite the central role of amyloid deposition in the development of Alzheimer's disease (AD), the pathogenesis of AD still remains elusive at the molecular level. Increasing evidence suggests that compromised mitochondrial function contributes to the aging process and thus may increase the risk of AD. Dysfunctional mitochondria contribute to reactive oxygen species (ROS) which can lead to extensive macromolecule oxidative damage and the progression of amyloid pathology. Oxidative stress and amyloid toxicity leave neurons chemically vulnerable. Because the brain relies on aerobic metabolism, it is apparent that mitochondria are critical for the cerebral function. Mitochondrial DNA sequence changes could shift cell dynamics and facilitate neuronal vulnerability. Therefore we postulated that mitochondrial DNA sequence polymorphisms may increase the risk of AD. We evaluated the role of mitochondrial haplogroups derived from 138 mitochondrial polymorphisms in 358 Caucasian Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Our results indicate that the mitochondrial haplogroup UK may confer genetic susceptibility to AD independently of the apolipoprotein E4 (APOE4) allele.

Comparative Phylogeny and Historical Perspectives on Population Genetics of the Pacific Hawksbill (Eretmochelys imbricata) and Green Turtles (Chelonia mydas), Inferred from Feeding Populations in the Yaeyama Islands, Japan

Mitochondrial DNA sequence polymorphisms and patterns of genetic diversity represent the genealogy and relative impacts of historical, geographic, and demographic events on populations. In this study, historical patterns of population dynamics and differentiation in hawksbill (Eretmochelys imbricata) and green turtles (Chelonia mydas) in the Pacific were estimated from feeding populations in the Yaeyama Islands, Japan. Phylogenetic relationships of the haplotypes indicated that hawksbill and green turtles in the Pacific probably underwent very similar patterns and processes of population dynamics over the last million years, with population subdivision during the early Pleistocene and population expansion after the last glacial maximum. These significant contemporary historical events were suggested to have been caused by climatic and sea-level fluctuations. On the other hand, comparing our results to long-term population dynamics in the Atlantic, population subdivisions during the early Pleistocene were specific to Pacific hawksbill and green turtles. Therefore, regional differences in historical population dynamics are suggested. Despite limited sampling locations, these results are the first step in estimating the historical trends in Pacific sea turtles by using phylogenetics and population genetics.

Biology, ecology and status of Iberian ibex Capra pyrenaica: a critical review and research prospectus

ABSTRACT The Iberian ibex Capra pyrenaica is endemic to the Iberian Peninsula and of the four subspecies originally recognized, recent extinctions mean that only two now persist. Recent genetic analyses have cast doubt on the generally accepted taxonomy of the species, where four subspecies were distinguished by coat colour and horn morphology, and propose the distinction of two subspecies based on their mitochondrial DNA sequence polymorphism. These analyses make clear the need for a comprehensive revision that integrates genetic and morphological approaches resulting in a definitive description and differentiation of the subspecies. Studies of ibex behavioural ecology and health status are scarce and generally descriptive. They should be implemented in an integrative way, taking into account the ecological requirements of the species, current population status, the presence of other sympatric wild and domestic ungulates, and the type of hunting regime and management in their distribution areas. A natural expansion of the species is currently taking place. Ibexes are present and well established in all the main mountain ranges of the Spanish Iberian Peninsula, and have recently expanded their range into the north of Portugal. Other authors estimated a total population of more than 50 000 individuals 10 years ago, distributed over more than 60 000 km2, with an average population density of 2.7 ibex/km2. However, these estimates were obtained prior to the species' recovery from recent epizootics of sarcoptic mange and should be updated. Survey methods, mainly direct count‐based methods, should be adjusted to suit mountainous conditions, where it is difficult to estimate accurately the surveyed surface. A series of threats to ibex conservation have been identified, such as population overabundance, disease prevalence and potential competition with domestic livestock and invasive ungulates, along with negative effects of human disturbance through tourism and hunting. Applied ecological issues focused on the proper management of populations should be prioritized, along with the identification of current threats based on empirical, ecological data obtained from populations living in various ecological conditions in different regions.

MALDI-TOF MS analysis of Y-SNPs in ancient samples

Studying ancient central Asian, Siberian and South American populations with classical markers (nuclear microsatellites and mitochondrial DNA sequence polymorphisms) allowed us to investigate parental relationships among individuals from burial sites revealing funeral practices. Ancient DNA studies can also provide information on the origins and the history of population from the past. Focussing on biallelic markers which have a lower mutation rate than repeat polymorphism, it is possible to address events corresponding to longer periods of time. In the frame of our anthropological studies on ancient DNA samples from Mongolia, Siberia, Yakutia and South America, we concentrated efforts on three Y chromosomal SNPs (TAT, M242 and RPS4Y) known to have specific allelic distributions in these populations or to be informative regarding the peopling of America (M242 and RPS4Y). Facing ancient samples where DNA is strongly degraded and scarce requires the use of technologies which can provide information from only short fragments of intact template. In this context, we developed a primer extension and matrix-assisted laser desorption ionization time-of-flight mass spectrometry-based multiplexed reaction for the investigation of these three polymorphisms. The tested ancient male specimens were recovered from a necropolis located south of Lake Baïkal in northern Mongolia (Egyin Gol valley). Distinct SNP profiles were obtained enlightening the ethnic heterogeneity of the Xiongnu tribe which was only foreshadowed by the STR marker analysis.

Trace of Native Cattle in Japanese Holstein Assessed by Mitochondrial DNA Sequence Polymorphism

On the basis of sequence variation in the displacement loop region of mtDNA, 588 Japanese and North American Holstein cows were classified into 5 mitochondrial haplotypes, which were found in Japanese Black cattle. One of the haplotypes (named type 1), which was present at the highest frequency in Japanese Black cattle, was not observed in either European or African cattle. This haplotype is characterized by 2 single-nucleotide polymorphisms. One is called the type B polymorphism, and it refers to a base change from T to C at nucleotide 16042 of the mitochondrial genome (T160042C). The other is called the type I polymorphism, and it refers to the base change as G16093A. The proportion of the Japanese Holstein population with both polymorphisms was 18.3%, whereas none of the North American cows had this genotype. Because the mitochondrial types were inherited maternally, it is clear that a considerable number of Japanese Holstein cows are descended from native Japanese cattle. Polymorphisms B and I accounted for no variance in the estimated breeding value for milk production among cows from the Hyogo herd (582 cows) or the Chiba region herd (758 cows). This result suggests that most autosomal genes of native animals have been successively replaced by those of pure Holstein after grading up of over 15 generations, even though resulting animals have native animal-oriented mitochondrial types and may still have some number of the native autosomal genes.

Tracing the dawn of Plasmodium falciparum with mitochondrial genome sequences

Until recently, little light had been shed on the murky origins of human malaria. Did Plasmodium falciparum, the most virulent malaria parasite, emerge as a common pathogen only in the past few thousand years, as suggested by some analyses of its nucleotide sequence diversity? Or, was it an ancient scourge of early humans >100 000 years ago, as suggested by others? A recent study, using complete mitochondrial DNA sequence polymorphism data and new analytical methods, points to an intermediate date of origin and expansion out of Africa. Subsequent population growth in each continent is less well resolved.

Mitochondrial DNA sequence polymorphisms of five ethnic populations from northern China.

To study the mitochondrial DNA (mtDNA) polymorphisms in a total of 232 individuals from five ethnic populations (Daur, n=45; Ewenki, n=47; Korean, n=48; Mongolian, n=48; Oroqen, n=44) in northern China, we analyzed the control region sequences and typed for a number of characteristic mutations in coding regions (especially the region 14576-16047), by direct sequencing or restriction-fragment-length-polymorphism (RFLP) analysis. With the exception of 14 individuals belonging to the European-specific haplogroups R2, H, J, and T, the mtDNAs considered could be assigned into the East Asian-specific haplogroups described recently. The polymorphisms in cytochrome b sequence were found to be very informative for defining or supporting the haplogroups status of East Asian mtDNAs in addition to the reported regions 10171-10659 and 14055-14590 in our previous study. The haplogroup distribution frequencies varied in the five ethnic populations, but in general they all harbored a large amount of north-prevalent haplogroups, such as D, G, C, and Z, and thus were in agreement with their ethnohistory of northern origin. The two populations (Ewenki and Oroqen) with small population census also show concordant features in their matrilineal genetic structures, with lower genetic diversities observed.

High-performance genetic analysis using microfabricated capillary array electrophoresis microplates

This review focuses on some recent advances in realizing microfabricated capillary array electrophoresis (microCAE). In particular, the development of a novel rotary scanning confocal fluorescence detector has facilitated the high-speed collection of sequencing and genotyping data from radially formatted microCAE devices. The concomitant development of a convenient energy-transfer cassette labeling chemistry allows sensitive multicolor labeling of any DNA genotyping or sequencing analyte. High-performance hereditary haemochromatosis and short tandem repeat genotyping assays are demonstrated on these devices along with rapid mitochondrial DNA sequence polymorphism analysis. Progress in supporting technology such as robotic fluid dispensing and batched data analysis is also presented. The ultimate goal is to develop a parallel analysis platform capable of integrated sample preparation and automated electrophoretic analysis with a throughput 10-100 times that of current technology.

Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA

The origin and geographical spread of Plasmodium falciparum is here determined by analysis of mitochondrial DNA sequence polymorphism and divergence from its most closely related species P. reichenowi (a rare parasite of chimpanzees). The complete 6 kb mitochondrial genome was sequenced from the single known isolate of P. reichenowi and from four different cultured isolates of P. falciparum, and aligned with the two previously derived P. falciparum sequences. The extremely low synonymous nucleotide polymorphism in P. falciparum ( π=0.0004) contrasts with the divergence at such sites between the two species ( K=0.1201), and supports a hypothesis that P. falciparum has recently emerged from a single ancestral population. To survey the geographical distribution of mitochondrial haplotypes in P. falciparum, 104 isolates from several endemic areas were typed for each of the identified single nucleotide polymorphisms. The haplotypes show a radiation out of Africa, with unique types in Southeast Asia and South America being related to African types by single nucleotide changes. This indicates that P. falciparum originated in Africa and colonised Southeast Asia and South America separately.

RELATIONSHIP BETWEEN MITOCHONDRIAL OXYGEN CONSUMPTION AND AEROBIC CAPACITY

1901 Recently, the relationship between mitochondrial DNA sequence polymorphism and inter individual difference in VO2max has been suggested. The purpose of this study was to determine the relationship between whole body aerobic capacity and individual mitochondrial electron transport enzymes which were encoded by mitochondrial DNA. Platelets, which did not have nuclear DNA but had mitochondiral DNA, was obtained from male elite (world class) endurance athletes (A) and sedentary controls (C). These platelets were fused with the ρ0HeLa cells, which completely lack mitochondrial DNA, and cybrid clones were isolated and were grown in medium. The enzymes of electron transport chain of the cybrid cells are encoded by subjectŌs mitochondrial DNA and HeLa cell's nuclear DNA. This model enabled us to compare the effects of mitochondiral DNA polymorphism on the mitochondrial function. The average cellular oxygen consumption of A was 18.2 ± 4.47 (mean ± SD) (nmol/min/107 cells) and C was 18.2 ± 4.15 (nmol/min/107 cells). There was no significant difference in cellular oxygen consumption between A and C. The result suggests that the mitochondiral DNA has less effect on the whole body aerobic capacity.

Mitochondrial DNA sequence polymorphism, VO2max, and response to endurance training.

Mitochondrial DNA sequence variation was determined in 46 sedentary young adult males who took part in ergocycle endurance training programs in two laboratories to assess whether mitochondrial DNA variants were associated with individual differences in maximal oxygen uptake (VO2max) and its response to training. VO2max was obtained from a progressive ergocycle test to exhaustion. White blood cell mitochondrial DNA was characterized with the restriction fragment length polymorphism (RFLP) technique using 22 restriction enzymes and human mitochondrial DNA as a probe for hybridization. Multiple mitochondrial DNA variants were detected with 15 of the enzymes. Some subjects exhibited many RFLPs, while others showed no variation. These RFLPs (morphs) were generated by base substitutions located in gene regions coding for mitochondrial proteins as well as in the noncoding regions. Carriers of three mitochondrial DNA morphs, two in the subunit 5 of the NADH dehydrogenase gene and one in the tRNA for threonine, had a VO2max (ml.kg-1.min-1) in the untrained state significantly higher than noncarriers, while carriers of one mitochondrial DNA morph in subunit 2 of NADH dehydrogenase had a lower initial VO2max. Endurance training increased VO2max by a mean of 0.5 l of O2, with individual differences ranging from gains of 0.06 to 1.03. After adjustment for training site and initial VO2max, a lower response was observed for three carriers of a variant in subunit 5 of the NADH dehydrogenase detected with HincII (mean gain of 0.28 l; P < 0.05). These results suggest that sequence variation in mitochondrial DNA may contribute to individual difference in VO2max and its response to training.

Mitochondrial DNA sequence polymorphism, VO2max, and response to endurance training

DIONNE, F. T., L. TURCOTTE, M.-C., THIBAULT, M. R. BOULAY, J. S. SKINNER, and C. BOUCHARD. Mitochondrial DNA sequence polymorphism, VO2max, and response to endurance training. Med. Sci. Sports Exerc., Vol. 23, No. 2, pp. 177–185, 1991. Mitochondrial DNA sequence variation was determined in 46 sedentary young adult males who took part in ergocycle endurance training programs in two laboratories to assess whetther mitochondrial DNA variants were associated with individual differences in maximal oxygen uptake (VO2max) and its response to training. VO2max was obtained from a progressive ergocycle test to exhaustion. White blood cell mitochondrial DNA was characterized with the restriction fragment length polymorphism (RFLP) technique using 22 restriction enzymes and human mitochondrial DNA as a probe for hybridization. Multiple mitochondrial DNA variants were detected with 15 of the enzymes. Some subjects exhibited many RFLPs, while others showed no variation. These RFLPs (morphs) were generated by base substitutions located in gene regions coding for mitochondrial proteins as well as in the noncoding regions. Carriers of three mitochondrial DNA morphs, two in the subunit 5 of the NADH dehydrogenase gene and one in the tRNA for threonine, had a VO2max (ml.kg-1.min-1) in the untrained state significantly higher than noncarriers, while carriers of one mitochondrial DNA morph in subunit 2 of NADH dehydrogenase had a lower initial VO2max. Endurance training increased VO2max, by a mean of 0.51 of O2, with individual differences ranging from gains of 0.06 to 1.03. After adjustment for training site and initial VO2max, a lower response was observed for three carriers of a variant in subunit 5 of the NADH dehydrogenase detected with Hincil (mean gain of 0.28 l; P<0.05). These results suggest that sequence variation in mitochondrial DNA may contribute to individual difference in VO2max and its response to training.