Distribution of mtDNA haplogroup X among Native North Americans.

Mitochondrial DNA (mtDNA) samples of 70 Native Americans, most of whom had been found not to belong to any of the four common Native American haplogroups (A, B, C, and D), were analyzed for the presence of Dde I site losses at np 1715 and np 10394. These two mutations are characteristic of haplogroup X which might be of European origin. The first hypervariable segment (HVSI) of the non-coding control region (CR) of mtDNA of a representative selection of samples exhibiting these mutations was sequenced to confirm their assignment to haplogroup X. Thirty-two of the samples exhibited the restriction site losses characteristic of haplogroup X and, when sequenced, a representative selection (n = 11) of these exhibited the CR mutations commonly associated with haplogroup X, C --> T transitions at np 16278 and 16223, in addition to as many as three other HVSI mutations. The wide distribution of this haplogroup throughout North America, and its prehistoric presence there, are consistent with its being a fifth founding haplogroup exhibited by about 3% of modern Native Americans. Its markedly nonrandom distribution with high frequency in certain regions, as for the other four major mtDNA haplogroups, should facilitate establishing ancestor/descendant relationships between modern and prehistoric groups of Native Americans. The low frequency of haplogroups other than A, B, C, D, and X among the samples studied suggests a paucity of both recent non-Native American maternal admixture in alleged fullblood Native Americans and mutations at the restriction sites that characterize the five haplogroups as well as the absence of additional (undiscovered) founding haplogroups.     

Fine characterization of the Iceman's mtDNA haplogroup

Starting from specimens of the intestinal contents of the so-called Tyrolean Iceman or Otzi (5,350-5,100 years before present), it was possible by polymerase chain reaction to amplify fragments of the human mitochondrial DNA (mtDNA) control region that correspond to the sequence found in 1994 at the Munich and Oxford laboratories and which had been attributed to the original DNA of the mummy. The particularly favorable condition of the specimens, showing very low contamination levels, made it easier to extend the analyses to the coding region, which had not previously been considered. The mtDNA of the European population is currently divided into nine (H, T, U, V, W, X, I, J, and K) main groups (haplogroups). The K haplogroup, in particular, is composed of two (K1 and K2) subclusters. The results demonstrate that the Iceman's mtDNA belongs to the K1 subcluster, yet it does not fit any of the three known branches (a, b, and c) into which the K1 subcluster is presently divided. In addition, some other sites, reported to be linked to environmental adaptation or pathologies, were investigated.     

Relationship between seasonal cold acclimatization and mtDNA haplogroup in Japanese

Background

The purpose of this study was to elucidate the interaction between mtDNA haplogroup and seasonal variation that contributes to cold adaptation.

Methods

There were 15 subjects (seven haplotype D subjects and eight haplotype non-D subjects). In summer and winter, the subjects were placed in an environment where the ambient temperature dropped from 27 °C to 10 °C in 30 minutes. After that, they were exposed to cold for 60 minutes.

Results

In summer, the decrease in rectal temperature and increase in oxygen consumption was smaller and cold tolerance was higher in the haplotype non-D group than in the haplotype D group. In winter, no significant differences were seen in rectal temperature or oxygen consumption, but the respiratory exchange ratio decreased in the haplotype D group.

Conclusions

The results of the present study suggest that haplogroup D subjects are a group that changes energy metabolism more, and there appears to be a relationship between differences in cold adaptability and mtDNA polymorphism within the population. Moreover, group differences in cold adaptability seen in summer may decrease in winter due to supplementation by seasonal cold acclimatization.     

Spatial and temporal stability of mtDNA haplogroup frequencies in native North America

Mitochondrial DNA lineage frequencies in prehistoric Aleut, eastern Utah Fremont, Southwestern Anasazi, Pyramid Lake, and Stillwater Marsh skeletal samples from northwest Nevada and the Oneota of western Illinois are compared with those in 41 contemporary aboriginal populations of North America. The ancient samples range in age from 300 years to over 6,000 years. The results indicate that the prehistoric inhabitants of North America exhibit the same level of mtDNA variability as contemporary populations of the continent. Variation in modern mtDNA haplogroup frequencies is highly geographically structured, and the prehistoric samples exhibit the same geographic pattern of variation. This indicates that differentiation of regional patterns of mtDNA lineage variation occurred early in North American prehistory (much more than 2,000 years B.P.), has remained relatively stable since its origin, and was little influenced by the disruptions hypothesized for other genetic systems as a result of population declines and relocations at contact.     

mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese

Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (>3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL.     

An evolutionary perspective on pathogenic mtDNA mutations: haplogroup associations of clinical disorders

More than 75 human diseases have been associated with mitochondrial dysfunction, and many of these are directly caused by overtly pathogenic mutations in the mitochondrial genome (mtDNA). In addition, there have been a number of reports that posit a different, subtler role for mtDNA substitutions in the disease process. As we review here, mtDNA evolution has resulted in the distribution of sequences into continent-specific haplogroups, which are defined by a relatively small number of polymorphisms. Thus, mtDNA sequences can be assigned to European, African, or Asian/Native American haplogroups. There are numerous reports that various diseases are haplogroup-associated, and it has been suggested that some of these haplogroup-associated polymorphisms act as risk factors in these disorders. It has also been suggested that there are haplogroup-associations for aging. As we note here, however, such associations have usually been observed only in single studies and it is difficult to draw broad conclusions on the basis of the available evidence. At a minimum, we suggest that, a haplogroup-group association must be detected in multiple subpopulations or in a large, carefully controlled population survey.     

Disuniting uniformity: a pied cladistic canvas of mtDNA haplogroup H in Eurasia

It has been often stated that the overall pattern of human maternal lineages in Europe is largely uniform. Yet this uniformity may also result from an insufficient depth and width of the phylogenetic analysis, in particular of the predominant western Eurasian haplogroup (Hg) H that comprises nearly a half of the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence information from 267 mtDNA Hg H sequences, we have analyzed 830 mtDNA genomes, from 11 European, Near and Middle Eastern, Central Asian, and Altaian populations. In addition to the seven previously specified subhaplogroups, we define fifteen novel subclades of Hg H present in the extant human populations of western Eurasia. The refinement of the phylogenetic resolution has allowed us to resolve a large number of homoplasies in phylogenetic trees of Hg H based on the first hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125 polymorphic positions in HVS-I were found to be mutated in more than one subcluster of Hg H. The phylogeographic analysis revealed that sub-Hgs H1*, H1b, H1f, H2a, H3, H6a, H6b, and H8 demonstrate distinct phylogeographic patterns. The monophyletic subhaplogroups of Hg H provide means for further progress in the understanding of the (pre)historic movements of women in Eurasia and for the understanding of the present-day genetic diversity of western Eurasians in general.     

Mitochondrial DNA variant 11719G is a marker for the mtDNA haplogroup cluster HV

Based on sequencing data and results obtained from applying a tailored mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, we report that the G allele of the mitochondrial DNA (mtDNA) polymorphism at nucleotide position 11719 is associated with the European mtDNA haplogroup cluster HV, and that 11719A is therefore the ancestral allele.     

mtDNA haplogroup distribution in Chinese patients with Leber's hereditary optic neuropathy and G11778A mutation

Mitochondrial DNA background has been shown to be involved in the penetrance of Leber’s hereditary optic neuropathy (LHON) in western Eurasian populations. To analyze mtDNA haplogroup distribution pattern in Han Chinese patients with LHON and G11778A mutation, we analyzed the mtDNA haplogroups of 41 probands with LHON known to harbor G11778A mutation by sequencing the mtDNA control region hypervariable segments and some coding region polymorphisms. Each mtDNA was classified according to the available East Asian haplogroup system. The haplogroup distribution pattern of LHON sample was then compared to the reported Han Chinese samples. Haplogroups M7, D, B, and A were detected in 11 (26.8%), 10 (24.4%), 8 (19.5%), and 5 (12.2%) LHON families, respectively, and accounted for 82.9% of the total samples examined. For the remaining seven mtDNAs, six belonged to M8a, M10a, C, N9a, F1a, and R11, respectively, and one could only be assigned into macro-haplogroup M. The LHON sample was distinguished from other Han Chinese samples in the principal component map based on haplogroup distribution frequency. Our results show that matrilineal genetic components of Chinese LHON patients with G11778A are diverse and differ from related Han Chinese regional samples. mtDNA background might affect the expression of LHON and the G11778A mutation in Chinese population.     

An update to MitoTool: Using a new scoring system for faster mtDNA haplogroup determination

The determination of human mitochondrial DNA (mtDNA) haplogroups is not only crucial in anthropological and forensic studies, but is also helpful in the medical field to prevent establishment of wrong disease associations. In recent years, high-throughput technologies and the huge amounts of data they create, as well as the regular updates to the mtDNA phylogenetic tree, mean that there is a need for an automated approach which can make a speedier determination of haplogroups than can be made by using the traditional manual method. Here, we update the MitoTool (www.mitotool.org) by incorporating a novel scoring system for the determination of mtDNA into haplogroups, which has advantages on speed, accuracy and ease of implementation. In order to make the access to MitoTool easier, we also provide a stand-alone version of the program that will run on a local computer and this version is freely available at the MitoTool website.     

Origin and evolution of X chromosome inactivation

Evolution of the mammalian sex chromosomes heavily impacts on the expression of X-encoded genes, both in marsupials and placental mammals. The loss of genes from the Y chromosome forced a two-fold upregulation of dose sensitive X-linked homologues. As a corollary, female cells would experience a lethal dose of X-linked genes, if this upregulation was not counteracted by evolution of X chromosome inactivation (XCI) that allows for only one active X chromosome per diploid genome. Marsupials rely on imprinted XCI, which inactivates always the paternally inherited X chromosome. In placental mammals, random XCI (rXCI) is the predominant form, inactivating either the maternal or paternal X. In this review, we discuss recent new insights in the regulation of XCI. Based on these findings, we propose an X inactivation center (Xic), composed of a cis-Xic and trans-Xic that encompass all elements and factors acting to control rXCI either in cis or in trans. We also highlight that XCI may have evolved from a very small nucleation site on the X chromosome in the vicinity of the Sox3 gene. Finally, we discuss the possible evolutionary road maps that resulted in imprinted XCI and rXCI as observed in present day mammals.     

Dynamics of haplogroup frequencies and survival rates in a contact zone of two mtDNA lineages of the lizard Lacerta vivipara

The analysis of contact zones between lineages that were previously isolated in allopatry can lead to important insights on evolutionary processes such as selection and adaptation. In this paper we conducted a comparative demographic study of two mitochondrial DNA (mtDNA) lineages of the lizard Lacerta vivipara in the western Pyrénées to provide detail on the dynamics of their contact zone. By surveying haplogroup frequency across the contact area, we revealed the existence of a stable and very narrow contact zone between two parapatric lineages, which we infer to demonstrate a role for selection in the maintenance of this contact zone. We suggest these two lineages evolved in allopatry after retreating to different refugia during the Pleistocene glaciations, and subsequently came into secondary contact after the last glacial maximum. Although haplogroup frequencies were stable over time, we found significant age and environment (temperature) dependent survival differences between mtDNA haplogroups in one contact population sampled yearly from 2002 to 2009. Therefore, temperature‐induced demographic differences between the two mtDNA lineages may be responsible for the stability of this narrow contact zone. This is one of the first demographic studies conducted under natural conditions indicating the possibility of selection on mtDNA.     

中国山羊mtDNA D-loop遗传多样性及其起源研究

采用DNA测序技术分析了中国9个山羊品种（板角山羊、成都麻羊、贵州黑山羊、贵州白山羊、黔北麻羊、马头山羊、陕南白山羊、黄淮山羊和雷州山羊）共计128个个体的mtDNA D-loop全序列。结果表明：山羊mtDNA D-loop全序列长度为1212-1213bp,检测到102个变异位点,约占分析位点总数的8．42％,可变位点中转换占99个,颠换2个,1个转换/颠换共存;界定了92种单倍型,有78种为各品种独享单倍型,另外14种为群体内或群体间共享单倍型。9个山羊品种单倍型多样度为0．9333-1．0000,核苷酸多样度为0．7062％-1．8265％,表明中国山羊品种遗传多样性丰富。根据92种mtDNA单倍型构建了中国山羊的NJ分子系统树,聚类表明,中国山羊mtDNA D-loop序列单倍型分为支系A和支系B两大类。支系A包括75种单倍型,代表95个样本,占总数的74．22％;支系B包括17种单倍型,代表33个样本,占总数的25．78％,说明中国山羊存在支系A和支系B两大母系起源。对中国山羊mtDNA D-loop的支系A和支系B进行核苷酸不配对分布曲线分析和Fu的Fs中性检验,分析表明,支系A的分布曲线呈单峰形,Fs值为-24．6491,P值为0．0000,显著偏离中性,表明山羊支系A曾经历群体扩张;支系B呈近似双峰分布,Fs值为-3．3947,P值为0．0980,中性检验差异不显著,表明山羊支系B没有经历群体扩张,群体大小保持相对稳定。山羊支系B可能起源于中国。     

The Genetic Diversity of mtDNA D-loop and the Origin of Chinese Goats

The complete sequences of mitochondrial DNA D-loop of 128 individuals in nine Chinese goat (Capra hircu) breeds were analyzed by DNA sequencing technology. The results show that the length of mtDNA D-loop in Chinese goats is 1 212-1 213 bp. There are 102 polymorphic sites, accounting for 8.42% of 1 212 bp sequence. Ninety-two mtDNA haplotypes were determined. The haplotype diversity and nucleotide diversity are 0.9333-1 .0000 and 0.7062%-1.8265%, respectively. The results indicate that the genetic diversity of Chinese goats is very abundant. The NJ tree indicates that Chinese goats have two types of maternal origins from lineage A and lineage B. The possibility of lineage B originating from China is also discussed.     

Origin and evolution of Native American mtDNA variation: a reappraisal.

The timing and number of prehistoric migrations involved in the settlement of the American continent is subject to intense debate. Here, we reanalyze Native American control region mtDNA data and demonstrate that only an appropriate phylogenetic analysis accompanied by an appreciation of demographic factors allows us to discern different migrations and to estimate their ages. Reappraising 574 mtDNA control region sequences from aboriginal Siberians and Native Americans, we confirm in agreement with linguistic, archaeological and climatic evidence that (i) the major wave of migration brought one population, ancestral to the Amerinds, from northeastern Siberia to America 20,000-25,000 years ago and (ii) a rapid expansion of a Beringian source population took place at the end of the Younger Dryas glacial phase approximately 11,300 years ago, ancestral to present Eskimo and Na-Dene populations.     

Lineage-specific selection in human mtDNA: lack of polymorphisms in a segment of MTND5 gene in haplogroup J

Human mitochondrial DNA (mtDNA) is a nonrecombining genome that codes for 13 subunits of the mitochondrial oxidative phosphorylation system, 2 rRNAs, and 22 tRNAs. Mutations have accumulated sequentially in mtDNA lineages that diverged tens of thousands of years ago. The genes in mtDNA are subject to different functional constraints and are therefore expected to evolve at different rates, but the rank order of these rates should be the same in all lineages of a phylogeny. Previous studies have indicated, however, that specific regions of mtDNA may have experienced different histories of selection in different lineages, possibly because of lineage-specific interactions or environmental factors such as climate. We report here on a survey for lineage-specific patterns of nucleotide polymorphism in human mtDNA. We calculated molecular polymorphism indices and neutrality tests for classes of functional sites and genes in 837 human mtDNA sequences, compared the results between continent-specific mtDNA lineages, and used two sliding window methods to identify differences in the patterns of polymorphism between haplogroups. A general correlation between nucleotide position and the level of nucleotide polymorphism was identified in the coding region of the mitochondrial genome. Nucleotide diversity in the protein-coding sequence of mtDNA was generally not much higher than that found for many genes in nuclear DNA. A comparison of nonsynonymous/synonymous rate ratios in the 13 protein-coding genes suggested differences in the relative levels of selection between haplogroups, including the European haplogroup clusters. Interestingly, a segment of the MTND5 gene was found to be almost void of segregating sites and nonsynonymous mutations in haplogroup J, which has been associated with susceptibility to certain complex diseases. Our results suggest that there are haplogroup-specific differences in the intensity of selection against particular regions of the mitochondrial genome, indicating that some mutations may be non-neutral within specific phylogenetic lineages but neutral within others.