mtDNA variation of aboriginal Siberians reveals distinct genetic affinities with Native Americans.

The mtDNA variation of 411 individuals from 10 aboriginal Siberian populations was analyzed in an effort to delineate the relationships between Siberian and Native American populations. All mtDNAs were characterized by PCR amplification and restriction analysis, and a subset of them was characterized by control region sequencing. The resulting data were then compiled with previous mtDNA data from Native Americans and Asians and were used for phylogenetic analyses and sequence divergence estimations. Aboriginal Siberian populations exhibited mtDNAs from three (A, C, and D) of the four haplogroups observed in Native Americans. However, none of the Siberian populations showed mtDNAs from the fourth haplogroup, group B. The presence of group B deletion haplotypes in East Asian and Native American populations but their absence in Siberians raises the possibility that haplogroup B could represent a migratory event distinct from the one(s) which brought group A, C, and D mtDNAs to the Americas. Our findings support the hypothesis that the first humans to move from Siberia to the Americas carried with them a limited number of founding mtDNAs and that the initial migration occurred between 17,000-34,000 years before present.     

mtDNA diversity in Chukchi and Siberian Eskimos: implications for the genetic history of Ancient Beringia and the peopling of the New World.

The mtDNAs of 145 individuals representing the aboriginal populations of Chukotka-the Chukchi and Siberian Eskimos-were subjected to RFLP analysis and control-region sequencing. This analysis showed that the core of the genetic makeup of the Chukchi and Siberian Eskimos consisted of three (A, C, and D) of the four primary mtDNA haplotype groups (haplogroups) (A-D) observed in Native Americans, with haplogroup A being the most prevalent in both Chukotkan populations. Two unique haplotypes belonging to haplogroup G (formerly called "other" mtDNAs) were also observed in a few Chukchi, and these have apparently been acquired through gene flow from adjacent Kamchatka, where haplogroup G is prevalent in the Koryak and Itel'men. In addition, a 16111C-->T transition appears to delineate an "American" enclave of haplogroup A mtDNAs in northeastern Siberia, whereas the 16192C-->T transition demarcates a "northern Pacific Rim" cluster within this haplogroup. Furthermore, the sequence-divergence estimates for haplogroups A, C, and D of Siberian and Native American populations indicate that the earliest inhabitants of Beringia possessed a limited number of founding mtDNA haplotypes and that the first humans expanded into the New World approximately 34,000 years before present (YBP). Subsequent migration 16,000-13,000 YBP apparently brought a restricted number of haplogroup B haplotypes to the Americas. For millennia, Beringia may have been the repository of the respective founding sequences that selectively penetrated into northern North America from western Alaska.     

Mitochondrial DNA variation in Koryaks and Itel'men: Population replacement in the Okhotsk Sea–Bering Sea region during the neolithic

In this study, we analyzed the mitochondrial DNA (mtDNA) variation in 202 individuals representing one Itel'men and three Koryak populations from different parts of the Kamchatka peninsula. All mtDNAs were subjected to high resolution restriction (RFLP) analysis and control region (CR) sequencing, and the resulting data were combined with those available for other Siberian and east Asian populations and subjected to statistical and phylogenetic analysis. Together, the Koryaks and Itel'men were found to have mtDNAs belonging to three (A, C, and D) of the four major haplotype groups (haplogroups) observed in Siberian and Native American populations (A–D). In addition, they exhibited mtDNAs belonging to haplogroups G, Y, and Z, which were formerly called “Other” mtDNAs. While Kamchatka harbored the highest frequencies of haplogroup G mtDNAs, which were widely distributed in eastern Siberian and adjacent east Asian populations, the distribution of haplogroup Y was restricted within a relatively small area and pointed to the lower Amur River–Sakhalin Island region as its place of origin. In contrast, the pattern of distribution and the origin of haplogroup Z mtDNAs remained unclear. Furthermore, phylogenetic and statistical analyses showed that Koryaks and Itel'men had stronger genetic affinities with eastern Siberian/east Asian populations than to those of the north Pacific Rim. These results were consistent with colonization events associated with the relatively recent immigration to Kamchatka of new tribes from the Siberian mainland region, although remnants of ancient Beringian populations were still evident in the Koryak and Itel'men gene pools. Am J Phys Anthropol 108:1–39, 1999. © 1999 Wiley‐Liss, Inc.     

mtDNA haplogroup X: An ancient link between Europe/Western Asia and North America?

On the basis of comprehensive RFLP analysis, it has been inferred that approximately 97% of Native American mtDNAs belong to one of four major founding mtDNA lineages, designated haplogroups "A"-"D." It has been proposed that a fifth mtDNA haplogroup (haplogroup X) represents a minor founding lineage in Native Americans. Unlike haplogroups A-D, haplogroup X is also found at low frequencies in modern European populations. To investigate the origins, diversity, and continental relationships of this haplogroup, we performed mtDNA high-resolution RFLP and complete control region (CR) sequence analysis on 22 putative Native American haplogroup X and 14 putative European haplogroup X mtDNAs. The results identified a consensus haplogroup X motif that characterizes our European and Native American samples. Among Native Americans, haplogroup X appears to be essentially restricted to northern Amerindian groups, including the Ojibwa, the Nuu-Chah-Nulth, the Sioux, and the Yakima, although we also observed this haplogroup in the Na-Dene-speaking Navajo. Median network analysis indicated that European and Native American haplogroup X mtDNAs, although distinct, nevertheless are distantly related to each other. Time estimates for the arrival of X in North America are 12,000-36,000 years ago, depending on the number of assumed founders, thus supporting the conclusion that the peoples harboring haplogroup X were among the original founders of Native American populations. To date, haplogroup X has not been unambiguously identified in Asia, raising the possibility that some Native American founders were of Caucasian ancestry.     

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.     

Mitochondrial DNA polymorphisms in Chilean aboriginal populations: implications for the peopling of the southern cone of the continent

The mitochondrial DNAs (mtDNAs) from individuals belonging to three Chilean tribes, the Mapuche, the Pehuenche, and the Yaghan, were studied both by RFLP analysis and D-loop (control region) sequencing. RFLP analysis showed that 3 individuals (1.3%) belonged to haplogroup A, 19 (8%) to haplogroup B, 102 (43%) to haplogroup C, and 113 (47.7%) to haplogroup D. Among the 73 individuals analyzed by D-loop sequencing, we observed 37 different haplotypes defined by 52 polymorphic sites. Joint analysis of data obtained by RFLP and sequencing methods demonstrated that, regardless of the method of analysis, the mtDNA haplotypes of these three contemporary South American aborigine groups clustered into four main haplogroups, in a way similar to those previously described for other Amerindians. These results further revealed the absence of haplogroup A in both the Mapuche and Yaghan as well as the absence of haplogroup B in the Yaghan. These results suggest that the people of Tierra del Fuego are related to tribes from south-central South America.     

A rare mitochondrial DNA haplotype observed in Koreans

The haplogroup affiliations of Korean mitochondrial DNAs (mtDNAs) were determined by restriction analysis. Out of the 101 mtDNAs analyzed, 91 (90%) belonged to Asian-specific haplogroups M, C, D, G, A, B, and F. Haplogroup E was not detected among the Korean mtDNAs. Three mtDNAs represented an unusual mtDNA haplotype characterized by simultaneous presence of E and G haplogroup-specific polymorphisms. To characterize this haplotype in more detail, we sequenced the hypervariable segment I (HVSI) from these mtDNAs as well as from those from selected individuals representing each haplogroup. Sequence data were further used to compare Korean mtDNAs with mtDNAs from other Asian populations. The observed rare haplotype was also found among Japanese, which suggests that it is one of the ancestral lineages originally peopling Japan.     

Uniparental genetic markers in South Amerindians

A comprehensive review of uniparental systems in South Amerindians was undertaken. Variability in the Y-chromosome haplogroups were assessed in 68 populations and 1,814 individuals whereas that of Y-STR markers was assessed in 29 populations and 590 subjects. Variability in the mitochondrial DNA (mtDNA) haplogroup was examined in 108 populations and 6,697 persons, and sequencing studies used either the complete mtDNA genome or the highly variable segments 1 and 2. The diversity of the markers made it difficult to establish a general picture of Y-chromosome variability in the populations studied. However, haplogroup Q1a3a* was almost always the most prevalent whereas Q1a3* occurred equally in all regions, which suggested its prevalence among the early colonizers. The STR allele frequencies were used to derive a possible ancient Native American Q-clade chromosome haplotype and five of six STR loci showed significant geographic variation. Geographic and linguistic factors moderately influenced the mtDNA distributions (6% and 7%, respectively) and mtDNA haplogroups A and D correlated positively and negatively, respectively, with latitude. The data analyzed here provide rich material for understanding the biological history of South Amerindians and can serve as a basis for comparative studies involving other types of data, such as cultural data.     

mtDNA and the origin of Caucasians: identification of ancient Caucasian-specific haplogroups, one of which is prone to a recurrent somatic duplication in the D-loop region.

mtDNA sequence variation was examined in 175 Caucasians from the United States and Canada by PCR amplification and high-resolution restriction-endonuclease analysis. The majority of the Caucasian mtDNAs were subsumed within four mtDNA lineages (haplogroups) defined by mutations that are rarely seen in Africans and Mongoloids. The sequence divergence of these haplogroups indicates that they arose early in Caucasian radiation and gave raise to modern European mtDNAs. Although ancient, none of these haplogroups is old enough to be compatible with a Neanderthal origin, suggesting that Homo sapiens sapiens displaced H. s. neanderthaliensis, rather than mixed with it. The mtDNAs of one of these haplogroups have a unique homoplasmic insertion between nucleotide pair (np) 573 and np 574, within the D-loop control region. This insertion makes these mtDNAs prone to a somatic mutation that duplicates a 270-bp portion of the D-loop region between np 309 and np 572. This finding suggests that certain nonpathogenic mtDNA mutations could predispose individuals to mtDNA rearrangements.     

Unexpected patterns of mitochondrial DNA variation among Native Americans from the southeastern United States

Mitochondrial DNA (mtDNA) haplogroups were determined by restriction fragment length polymorphism-typing for 66 individuals from four southeastern North American populations, and the HVS I portion of the mtDNA control region was sequenced in 48 of these individuals. Although populations from the same geographic region usually exhibit similar haplogroup frequency distributions (Lorenz and Smith [1996] Am. J. Phys. Anthropol. 101:307-323; Malhi et al. [2001] Hum. Biol. 73:17-55), those from the Southeast instead exhibit haplogroup frequency distributions that differ significantly from one another. Such divergent haplogroup frequency distributions are unexpected for the Muskogean-speaking southeastern populations, which share many sociocultural traits, speak closely related languages, and have experienced extensive admixture both with each other and with other eastern North American populations. Independent origins, genetic isolation from other Native American populations due to matrilocality, differential admixture, or a genetic bottleneck could be responsible for this heterogeneous distribution of haplogroup frequencies. Within a given haplogroup, however, the HVS I sequences from the four Muskogean-speaking populations appear relatively similar to one another, providing evidence for close relationships among them and for reduced diversity within haplogroups in the Southeast. Given additional archaeological, linguistic, and ethnographic evidence, these results suggest that a genetic bottleneck associated with the historical population decline is the most plausible explanation for such patterns of mtDNA variation.     

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.     

Native American Mitochondrial DNA Analysis Indicates That the Amerind and the Nadene Populations Were Founded by Two Independent Migrations

Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.     

The Dual Origin and Siberian Affinities of Native American Y Chromosomes

The Y chromosomes of 549 individuals from Siberia and the Americas were analyzed for 12 biallelic markers, which defined 15 haplogroups. The addition of four microsatellite markers increased the number of haplotypes to 111. The major Native American founding lineage, haplogroup M3, accounted for 66% of male Y chromosomes and was defined by the biallelic markers M89, M9, M45, and M3. The founder haplotype also harbored the microsatellite alleles DYS19 (10 repeats), DYS388 (11 repeats), DYS390 (11 repeats), and DYS391 (10 repeats). In Siberia, the M3 haplogroup was confined to the Chukotka peninsula, adjacent to Alaska. The second major group of Native American Y chromosomes, haplogroup M45, accounted for about one-quarter of male lineages. M45 was subdivided by the biallelic marker M173 and by the four microsatellite loci alleles into two major subdivisions: M45a, which is found throughout the Americas, and M45b, which incorporates the M173 variant and is concentrated in North and Central America. In Siberia, M45a haplotypes, including the direct ancestor of haplogroup M3, are concentrated in Middle Siberia, whereas M45b haplotypes are found in the Lower Amur River and Sea of Okhotsk regions of eastern Siberia. Among the remaining 5% of Native American Y chromosomes is haplogroup RPS4Y-T, found in North America. In Siberia, this haplogroup, along with haplogroup M45b, is concentrated in the Lower Amur River/Sea of Okhotsk region. These data suggest that Native American male lineages were derived from two major Siberian migrations. The first migration originated in southern Middle Siberia with the founding haplotype M45a (10-11-11-10). In Beringia, this gave rise to the predominant Native American lineage, M3 (10-11-11-10), which crossed into the New World. A later migration came from the Lower Amur/Sea of Okhkotsk region, bringing haplogroup RPS4Y-T and subhaplogroup M45b, with its associated M173 variant. This migration event contributed to the modern genetic pool of the Na-Dene and Amerinds of North and Central America.     

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.     

Frequency distribution of mitochondrial DNA haplogroups in Corsica and Sardinia

Mitochondrial DNA (mtDNA) polymorphisms were analyzed by polymerase chain reaction amplification and haplogroup-specific restriction screening in populations from Corsica and Sardinia. These included 56 individuals from the area of Corte, central Corsica (France), 51 individuals from Gallura, northern Sardinia (Italy), and 45 individuals from Barbagia, central Sardinia. The screening revealed that about 95% of mtDNAs could be grouped in 8 of the 9 European haplogroups, including H-K, T-V, and X. Our results confirmed that these haplogroups encompass virtually all the mitochondrial lineages present in Europe and can be detected in both northern and southern European populations. We also discovered 2 restriction sites (-73 Alw441 and +75 SphI) that allow the detection of informative nucleotide changes in the second hypervariable segment of the control region, which help to detect the haplogroup identity of mtDNAs without requiring further DNA sequencing. Haplogroup H was the most common mtDNA lineage in this sample, reaching frequencies from about 40% in Corsican and Gallurese populations, to about 65% in the Barbagian population. Haplogroup V, possibly originating in the Iberian peninsula, was found only in the central Sardinian sample. Of the 5 Corsican mtDNAs belonging to the haplogroup T, 4 had a restriction fragment length polymorphism found only in this population. It seems that this mutation originated in Corsica and has had time to spread in the area, since the maternal grandmothers of the subjects came from different villages of the island. The sample from central Sardinia shows a remarkable discontinuity with those from the northern part of the island and from Corsica. Gallura and Corsica seem to have undergone a more recent peopling event, possibly related to the arrival of new mitochondrial variability from continental Italy, while Barbagia has apparently maintained more archaic haplotypes.     

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.     

Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America

There is general agreement that the Native American founder populations migrated from Asia into America through Beringia sometime during the Pleistocene, but the hypotheses concerning the ages and the number of these migrations and the size of the ancestral populations are surrounded by controversy. DNA sequence variations of several regions of the genome of Native Americans, especially in the mitochondrial DNA (mtDNA) control region, have been studied as a tool to help answer these questions. However, the small number of nucleotides studied and the nonclocklike rate of mtDNA control-region evolution impose several limitations to these results. Here we provide the sequence analysis of a continuous region of 8.8 kb of the mtDNA outside the D-loop for 40 individuals, 30 of whom are Native Americans whose mtDNA belongs to the four founder haplogroups. Haplogroups A, B, and C form monophyletic clades, but the five haplogroup D sequences have unstable positions and usually do not group together. The high degree of similarity in the nucleotide diversity and time of differentiation (i.e., approximately 21,000 years before present) of these four haplogroups support a common origin for these sequences and suggest that the populations who harbor them may also have a common history. Additional evidence supports the idea that this age of differentiation coincides with the process of colonization of the New World and supports the hypothesis of a single and early entry of the ancestral Asian population into the Americas.     

Distribution of mitochondrial DNA lineages among Native American tribes of Northeastern North America

The mtDNA haplogroups of 185 individuals from Native American tribes in Northeast North America were determined. A subset of these individuals was analyzed by sequencing hypervariable segments I and II of the control region. The haplogroup frequency distributions of populations in the Northeast exhibit regional continuity that predates European contact. A large amount of gene flow has occurred between Siouan-and Algonquian-speaking groups, probably due to an Algonquian intrusion into the Northeast. The data also support both the Macro-Siouan hypothesis and a relatively recent intrusion of Northern Iroquoians into the Northeast. These conclusions are consistent with archaeological and linguistic evidence.     

Brief communication: molecular analysis of the Kwäday Dän Ts'finchi ancient remains found in a glacier in Canada

DNA was extracted from the frozen remains of a man found in the northwest corner of British Columbia, Canada, in 1999. His clothing was radiocarbon-dated at ca. 550 years old. Nitrogen and carbon content in whole bone and collagen-type residue extracted from both bone and muscle indicated good preservation of proteinaceous macromolecules. Restriction enzyme analysis of mitochondrial DNA (mtDNA) determined that the remains belong to haplogroup A, one of the four major Native American mtDNA haplogroups. Data obtained by PCR direct sequencing of the mtDNA control region, and by sequencing the clones from overlapping PCR products, were duplicated by an independent laboratory. Comparison of these mtDNA sequences with those of North American, Central American, South American, East Siberian, Greenlandic, and Northeast Asian populations indicates that the remains share an mtDNA type with North American, Central American, and South American populations.     

Linguistic and maternal genetic diversity are not correlated in Native Mexicans

Mesoamerica, defined as the broad linguistic and cultural area from middle southern Mexico to Costa Rica, might have played a pivotal role during the colonization of the American continent. The Mesoamerican isthmus has constituted an important geographic barrier that has severely restricted gene flow between North and South America in pre-historical times. Although the Native American component has been already described in admixed Mexican populations, few studies have been carried out in native Mexican populations. In this study, we present mitochondrial DNA (mtDNA) sequence data for the first hypervariable region (HVR-I) in 477 unrelated individuals belonging to 11 different native populations from Mexico. Almost all of the Native Mexican mtDNAs could be classified into the four pan-Amerindian haplogroups (A2, B2, C1, and D1); only two of them could be allocated to the rare Native American lineage D4h3. Their haplogroup phylogenies are clearly star-like, as expected from relatively young populations that have experienced diverse episodes of genetic drift (e.g., extensive isolation, genetic drift, and founder effects) and posterior population expansions. In agreement with this observation, Native Mexican populations show a high degree of heterogeneity in their patterns of haplogroup frequencies. Haplogroup X2a was absent in our samples, supporting previous observations where this clade was only detected in the American northernmost areas. The search for identical sequences in the American continent shows that, although Native Mexican populations seem to show a closer relationship to North American populations, they cannot be related to a single geographical region within the continent. Finally, we did not find significant population structure in the maternal lineages when considering the four main and distinct linguistic groups represented in our Mexican samples (Oto-Manguean, Uto-Aztecan, Tarascan, and Mayan), suggesting that genetic divergence predates linguistic diversification in Mexico.