Ancient mtDNA haplogroups: a new insight into the genetic history of European populations

In the present work, DNA was extracted from 63 skeletal samples recovered at the Neolithic site of San Juan ante Portam Latinam (SJAPL) (Araba, Basque Country). These samples have proved useful as genetic material for the performance of population studies. To achieve this it was necessary to overcome the methodological problems arising when working with damaged DNA molecules. We succeeded in performing an amplification and restriction analysis of the polymorphisms present in the mtDNA. Ninety seven percent of the samples were classified as belonging to one of the nine mtDNA haplogroups described in Caucasians. This work shows that restriction analysis is a useful methodological tool to perform reliable population genetic analysis on archaeological remains. Tha analysis of ancient and modern haplogroup distribution can shed more light on the genetic evolution of human populations. Moreover, a more exhaustive data on prehistoric populations will allow to build stronger hypothesis on the genetic relationships among human populations.     

Analysis of mtDNA variation in African populations reveals the most ancient of all human continent-specific haplogroups.

mtDNA sequence variation was examined in 140 Africans, including Pygmies from Zaire and Central African Republic (C.A.R.) and Mandenkalu, Wolof, and Pular from Senegal. More than 76% of the African mtDNAs (100% of the Pygmies and 67.3% of the Senegalese) formed one major mtDNA cluster (haplogroup L) defined by an African-specific HpaI site gain at nucleotide pair (np) 3592. Additional mutations subdivided haplogroup L into two subhaplogroups, each encompassing both Pygmy and Senegalese mtDNAs. A novel 12-bp homoplasmic insertion in the intergenic region between tRNA(Tyr) and cytochrome oxidase I (COI) genes was also observed in 17.6% of the Pygmies from C.A.R. This insertion is one of the largest observed in human mtDNAs. Another 25% of the Pygmy mtDNAs harbored a 9-bp deletion between the cytochrome oxidase II (COII) and tRNA(Lys) genes, a length polymorphism previously reported in non-African populations. In addition to haplogroup L, other haplogroups were observed in the Senegalese. These haplogroups were more similar to those observed in Europeans and Asians than to haplogroup L mtDNAs, suggesting that the African mtDNAs without the HpaI np 3592 site could be the ancestral types from which European and Asian mtDNAs were derived. Comparison of the intrapopulation sequence divergence in African and non-African populations confirms that African populations exhibit the largest extent of mtDNA variation, a result that further supports the hypothesis that Africans represent the most ancient human group and that all modern humans have a common and recent African origin. The age of the total African variation was estimated to be 101,000-133,000 years before present (YBP), while the age of haplogroup L was estimated at 98,000-130,000 YBP. These values substantially exceed the ages of all Asian- and European-specific mtDNA haplogroups.     

African Haplogroup L mtDNA sequences show violations of clock-like evolution

A set of 96 complete mtDNA sequences that belong to the three major African haplogroups (L1, L2, and L3) was analyzed to determine if mtDNA has evolved as a molecular clock. Likelihood ratio tests (LRTs) were carried out with each of the haplogroups and with combined haplogroup sequence sets. Evolution has not been clock-like, neither for the coding region nor for the control region, in combined sets of African haplogroup L mtDNA sequences. In tests of individual haplogroups, L2 mtDNAs showed violations of a molecular clock under all conditions and in both the control and coding regions. In contrast, haplogroup L1 and L3 sequences, both for the coding and control regions, show clock-like evolution. In clock tests of individual L2 subclades, the L2a sequences showed a marked violation of clock-like evolution within the coding region. In addition, the L2a and L2c branch lengths of both the coding and control regions were shorter relative to those of the L2b and L2d sequences, a result that indicates lower levels of sequence divergence. Reduced median network analyses of the L2a sequences indicated the occurrence of marked homoplasy at multiple sites in the control region. After exclusion of the L2a and L2c sequences, African mtDNA coding region evolution has not significantly departed from a molecular clock, despite the results of neutrality tests that indicate the mitochondrial coding region has evolved under nonneutral conditions. In contrast, control region evolution is clock-like only at the haplogroup level, and it thus appears to have evolved essentially independently from the coding region. The results of the clock tests, the network analyses, and the branch length comparisons all caution against the use of simple mtDNA clocks.     

The evolution of two west African populations

Summary The identification of genetically coherent populations is essential for understanding human evolution. Among the culturally uniform ethnic groups of west Africa, there are two geographically distinct populations with high frequencies of sickle-cell hemoglobin (HbS). Although the HbS mutation in each group is found on distinguishable chromosomes 11, these populations have been assumed to be parts of a single population. Analysis of mitochondrial DNA (mtDNA) in these populations demonstrated that the two populations identified by alternative chromosomes 11 bearing HbS have distinct distributions of mitochondrial genotypes, i.e., they are maternally separate. These studies also showed that, contrary to expectation, the mtDNA of some individuals is heteroplasmic. For nuclear loci, a comparison of the frequency of alternative alleles established that these populations are genetically distinct. Both the mitochondrial and nuclear data indicate that these populations have been separate for approximately 50,000 years. Although HbS in the two populations is usually attributed to recent, independent mutations, the duration of the separation and the observed geographic distribution of the population allow for the possibility of an ancient origin of HbS. Assuming an ancient mutation and considering the known biogeography, we suggest that HbS protected selected populations from malaria in rain forest refuges during the most recent ice age.Offprint requests to: O.C. Stine     

mtDNA variation in the South African Kung and Khwe-and their genetic relationships to other African populations

The mtDNA variation of 74 Khoisan-speaking individuals (Kung and Khwe) from Schmidtsdrift, in the Northern Cape Province of South Africa, was examined by high-resolution RFLP analysis and control region (CR) sequencing. The resulting data were combined with published RFLP haplotype and CR sequence data from sub-Saharan African populations and then were subjected to phylogenetic analysis to deduce the evolutionary relationships among them. More than 77% of the Kung and Khwe mtDNA samples were found to belong to the major mtDNA lineage, macrohaplogroup L* (defined by a HpaI site at nucleotide position 3592), which is prevalent in sub-Saharan African populations. Additional sets of RFLPs subdivided macrohaplogroup L* into two extended haplogroups-L1 and L2-both of which appeared in the Kung and Khwe. Besides revealing the significant substructure of macrohaplogroup L* in African populations, these data showed that the Biaka Pygmies have one of the most ancient RFLP sublineages observed in African mtDNA and, thus, that they could represent one of the oldest human populations. In addition, the Kung exhibited a set of related haplotypes that were positioned closest to the root of the human mtDNA phylogeny, suggesting that they, too, represent one of the most ancient African populations. Comparison of Kung and Khwe CR sequences with those from other African populations confirmed the genetic association of the Kung with other Khoisan-speaking peoples, whereas the Khwe were more closely linked to non-Khoisan-speaking (Bantu) populations. Finally, the overall sequence divergence of 214 African RFLP haplotypes defined in both this and an earlier study was 0.364%, giving an estimated age, for all African mtDNAs, of 125,500-165,500 years before the present, a date that is concordant with all previous estimates derived from mtDNA and other genetic data, for the time of origin of modern humans in Africa.     

Comparison of mtDNA haplogroups in Hungarians with four other European populations: a small incidence of descents with Asian origin

Hungarians are unique among the other European populations because according to history, the ancient Magyars had come from the eastern side of the Ural Mountains and settled down in the Carpathian basin in the 9th century AD. Since variations in the human mitochondrial genome (mtDNA) are routinely used to infer the histories of different populations, we examined the distribution of restriction fragment length polymorphism (RFLP) sites of the mtDNA in apparently healthy, unrelated Hungarian subjects in order to collect data on the genetic origin of the Hungarian population. Among the 55 samples analyzed, the large majority belonged to haplogroups common in other European populations, however, three samples fulfilled the requirements of haplogroup M. Since haplogroup M is classified as a haplogroup characteristic mainly for Asian populations, the presence of haplogroup M found in approximately 5% of the total suggests that an Asian matrilineal ancestry, even if in a small incidence, can be detected among modern Hungarians.     

Distribution of four founding mtDNA haplogroups among Native North Americans

The mtDNA of most Native Americans has been shown to cluster into four lineages, or haplogroups. This study provides data on the haplogroup affiliation of nearly 500 Native North Americans including members of many tribal groups not previously studied. Phenetic cluster analysis shows a fundamental difference among 1) Eskimos and northern Na-Dene groups, which are almost exclusively mtDNA haplogroup A, 2) tribes of the Southwest and adjacent regions, predominantly Hokan and Uto-Aztecan speakers, which lack haplogroup A but exhibit high frequencies of haplogroup B, 3) tribes of the Southwest and Mexico lacking only haplogroup D, and 4) a geographically heterogeneous group of tribes which exhibit varying frequencies of all four haplogroups. There is some correspondence between language group affiliations and the frequencies of the mtDNA haplogroups in certain tribes, while geographic proximity appears responsible for the genetic similarity among other tribes. Other instances of similarity among tribes suggest hypotheses for testing with more detailed studies. This study also provides a context for understanding the relationships between ancient and modern populations of Native Americans. © 1996 Wiley-Liss, Inc.     

MtDNA haplogroups in the populations of Croatian Adriatic Islands

The number of previous anthropological studies pointed to very complex ethnohistorical processes that shaped the current genetic structure of Croatian island isolates. The scope of this study was limited to the general insight into their founding populations and the overall level of genetic diversity based on the study mtDNA variation. A total of 444 randomly chosen adult individuals from 32 rural communities of the islands of Krk, Brac, Hvar and Korcula were sampled. MtDNA HVS-I region together with RFLP sites diagnostic for main Eurasian and African mtDNA haplogroups were analysed in order to determine the haplogroup structure. The most frequent haplogroups were "H" (27.8-60.2%), "U" (10.2-24.1%), "J" (6.1-9.0%) and "T" (5.1-13.9%), which is similar to the other European and Near Eastern populations. The genetic drift could have been important aspect in history, as there were examples of excess frequencies of certain haplogroups (11.3% of "I" and 7.5% of "W" in Krk, 10.5% of "HV" in Brac, 13.9% of "J" in Hvar and 60.2% of "H" in Korcula). As the settlements on the islands were formed trough several immigratory episodes of genetically distant populations, this analysis (performed at the level of entire islands) showed greater genetic diversity (0.940-0.972) than expected at the level of particular settlements.     

Role of mtDNA haplogroups in COPD susceptibility in a southwestern Han Chinese population

The interplay of a complex genetic basis with the environmental factors of chronic obstructive pulmonary disease (COPD) may account for the differences in individual susceptibility to COPD. Mitochondrial DNA (mtDNA) contributes to an individual's ability to resist oxidation, an important determinant that affects COPD susceptibility. To investigate whether mtDNA haplogroups play important roles in COPD susceptibility, the frequencies of mtDNA haplogroups and an 822-bp mtDNA deletion in 671 COPD patients and 724 control individuals from southwestern China were compared. Multivariate logistic regression analysis revealed that, whereas mtDNA haplogroups A and M7 might be associated with an increased risk for COPD (OR=1.996, 95% CI=1.149-2.831, p=0.006, and OR=1.754, 95% CI=1.931-2.552, p=0.021, respectively), haplogroups F, D, and M9 might be associated with a decreased risk for COPD in this population (OR=0.554, 95% CI=0.390-0.787, p=0.001; OR=0.758, 95% CI=0.407-0.965, p=0.002; and OR=0.186, 95% CI=0.039-0.881, p=0.034, respectively). Additionally, the increased frequency of the 822-bp mtDNA deletion in male cigarette-smoking subjects among COPD patients and controls of haplogroup D indicated that haplogroup D might increase an individual's susceptibility to DNA damage from external reactive oxygen species derived from heavy cigarette smoking. We conclude that haplogroups A and M7 might be risk factors for COPD, whereas haplogroups D, F, and M9 might decrease the COPD risk in this Han Chinese population.     

Rare mtDNA haplogroups and genetic differences in rich and poor Danish Iron-Age villages

The Roman Iron‐Age (0–400 AD) in Southern Scandinavia was a formative period, where the society changed from archaic chiefdoms to a true state formation, and the population composition has likely changed in this period due to immigrants from Middle Scandinavia. We have analyzed mtDNA from 22 individuals from two different types of settlements, Bøgebjerggård and Skovgaarde, in Southern Denmark. Bøgebjerggård (ca. 0 AD) represents the lowest level of free, but poor farmers, whereas Skovgaarde 8 km to the east (ca. 200–270 AD) represents the highest level of the society. Reproducible results were obtained for 18 subjects harboring 17 different haplotypes all compatible (in their character states) with the phylogenetic tree drawn from present day populations of Europe. This indicates that the South Scandinavian Roman Iron‐Age population was as diverse as Europeans are today. Several of the haplogroups (R0a, U2, I) observed in Bøgebjerggård are rare in present day Scandinavians. Most significantly, R0a, harbored by a male, is a haplogroup frequent in East Africa and Arabia but virtually absent among modern Northern Europeans. We suggest that this subject was a soldier or a slave, or a descendant of a female slave, from Roman Legions stationed a few hundred kilometers to the south. In contrast, the haplotype distribution in the rich Skovgaarde shows similarity to that observed for modern Scandinavians, and the Bøgebjerggård and Skovgaarde population samples differ significantly (P ≈ 0.01). Skovgaarde may represent a new upper‐class formed by migrants from Middle Scandinavia bringing with them Scandinavian haplogroups. Am J Phys Anthropol, 2008. © 2007 Wiley‐Liss, Inc.     

Mitochondrial DNA (mtDNA) haplogroups in 1526 unrelated individuals from 11 Departments of Colombia

The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest.     

Testing the adaptive selection of human mtDNA haplogroups: an experimental bioenergetics approach

The evolution of human mtDNA (mitochondrial DNA) has been characterized by the emergence of distinct haplogroups, which are associated with the major global ethnic groups and defined by the presence of specific mtDNA polymorphic variants. A recent analysis of complete mtDNA genome sequences has suggested that certain mtDNA haplogroups may have been positively selected as humans populated colder climates due to a decreased mitochondrial coupling efficiency, in turn leading to increased generation of heat instead of ATP synthesis by oxidative phosphorylation. If this is true, implying different evolutionary processes in different haplogroups, this could potentially void the usefulness of mtDNA as a genetic tool to study the timing of major events in evolutionary history. In this issue of the Biochemical Journal, Taku Amo and Martin Brand present experimental biochemical data to test this hypothesis. Measurements of the bioenergetic capacity of cybrid cells harbouring specific Arctic or tropical climate mtDNA haplogroups on a control nuclear background reveal no significant changes in coupling efficiency between the two groups, indicating that mtDNA remains a viable evolutionary tool to assess the timing of major events in the history of humans and other species.     

Frequencies of the four major Amerindian mtDNA haplogroups in the population of Montevideo, Uruguay

mtDNA Amerindian polymorphisms were studied in 108 inhabitants of Montevideo, Uruguay, using PCR RFLP analysis. Amerindian haplogroups were found in 20.4% of the sample. The frequency of Amerindian polymorphisms in Montevideo differed significantly from that observed in Tacuarembó, a city about 400 km away, indicating the high level of variation within Uruguay. Results for mitochondrial markers indicate that admixture occurred primarily as a result of Amerindian females mating with European males.     

Rapid deployment of the five founding Amerind mtDNA haplogroups via coastal and riverine colonization

Numerous studies of variation in mtDNA in Amerindian populations established that four haplogroups are present throughout both North and South America. These four haplogroups (A, B, C, and D) and perhaps a fifth (X) in North America are postulated to be present in the initial founding migration to the Americas. Furthermore, studies of ancient mtDNA in North America suggested long-term regional continuity of the frequencies of these founding haplogroups. Present-day tribal groups possess high frequencies of private mtDNA haplotypes (variants within the major haplogroups), consistent with early establishment of local isolation of regional populations. Clearly these patterns have implications for the mode of colonization of the hemisphere. Recently, the earlier consensus among archaeologists for an initial colonization by Clovis hunters arriving through an ice-free corridor and expanding in a "blitzkrieg " wave was shown to be inconsistent with extensive genetic variability in Native Americans; a coastal migration route avoids this problem. The present paper demonstrates through a computer simulation model how colonization along coasts and rivers could have rapidly spread the founding lineages widely through North America.     

Extreme mtDNA homogeneity in continental Asian populations

Mitochondrial DNA (mtDNA) variation in continental Asia has not been well-studied. Here, we report mtDNA HV1 sequences for 84 Xi'an and 82 Changsha Han Chinese, 89 Honshu Japanese, and 35 Vietnamese. Comparison of these sequences with other Asian mtDNA sequences reveals high variability within populations, but extremely low differentiation among Asian populations. Correlations between genetic distance and geographic distance, based on mtDNA and Y chromosome variation, indicate a higher migration rate in females than in males. This may reflect patrilocality, as suggested previously, but another plausible hypothesis is that the demographic expansion associated with the spread of agriculture in Asia may be responsible for the extreme genetic homogeneity in Asia.     

Mitochondrial DNA haplogroups in Amerindian populations from the Gran Chaco.

Mitochondrial DNA from 141 individuals was typed for diagnostic restriction sites and the 9-bp region V deletion to examine the distribution of the founding mtDNA lineage haplotypes in three Amerindian populations (Mataco, Toba, and Pilagá) who currently inhabit the Argentinian part of the Gran Chaco. All four lineages were identified in the three tribes and four population samples studied. Disregarding ethnic or geographic origin, haplogroups B and D exhibit high incidence among the Gran Chaco inhabitants, whereas haplogroups A and C are present in a lower frequency. Three individuals possess none of the characteristic markers and, therefore, could not be assigned to one of those lineages. A neighbor-joining representation of F(ST) distances reflects the current geographic location of the populations, and this also corresponds to their historic distribution. After separating South America into four major regions (Tropical Forest, Andes, Gran Chaco, and Patagonia-Tierra del Fuego), the Gran Chaco populations present the highest average intragroup variability (Hs = 0.64) as well as the lowest intergroup diversity (G(')(ST) = 0.06). These findings suggest high levels of gene flow among the Chaco tribes, as well as with neighbor populations from outside the region.     

线粒体DNA在分子进化研究中的应用

线粒体作为古老的细胞器广泛存在于真核生物中,由于线粒体DNA的高进化速率,已被作为DNA标记广泛应用于现代分子生物学研究。长期以来,线粒体DNA一直被认为是中性进化或者受到纯净化选择。线粒体通过氧化呼吸链提供>95%的动物运动所需的自由能,并提供保持体温的热能。据此,近期已有研究推测并验证了线粒体与动物运动能力及气候适应性的相关性。该文简述线粒体基因组成及其进化,通过列举线粒体DNA在分子进化研究中的应用(如利用线粒体DNA重建物种的系统发育关系、从线粒体DNA角度分析生物能量代谢的适应性进化以及线粒体DNA密码子重定义对生物适应性的作用等),概述了线粒体DNA的分子进化研究。