Untangling Neolithic and Bronze Age mitochondrial lineages in South Asia

Abstract

Two key moments shaped the extant South Asian gene pool within the last 10 thousand years (ka): the Neolithic period, with the advent of agriculture and the rise of the Harappan/Indus Valley Civilisation; and Late Bronze Age events that witnessed the abrupt fall of the Harappan Civilisation and the arrival of Indo-European speakers. This study focuses on the phylogeographic patterns of mitochondrial haplogroups H2 and H13 in the Indian Subcontinent and incorporates evidence from recently released ancient genomes from Central and South Asia. It found signals of Neolithic arrivals from Iran and later movements in the Bronze Age from Central Asia that derived ultimately from the Steppe. This study shows how a detailed mtDNA phylogeographic approach, combining both modern and ancient variation, can provide evidence of population movements, even in a scenario of strong male bias such as in the case of the Bronze Age Steppe dispersals.     

Mitochondrial haplogroup C in ancient mitochondrial DNA from Ukraine extends the presence of East Eurasian genetic lineages in Neolithic Central and Eastern Europe

Recent studies of ancient mitochondrial DNA (mtDNA) lineages have revealed the presence of East Eurasian mtDNA haplogroups in the Central European Neolithic. Here we report the finding of East Eurasian lineages in ancient mtDNA from two Neolithic cemeteries of the North Pontic Region (NPR) in Ukraine. In our study, comprehensive haplotyping information was obtained for 7 out of 18 specimens. Although the majority of identified mtDNA haplogroups belonged to the traditional West Eurasian lineages of H and U, three specimens were determined to belong to the lineages of mtDNA haplogroup C. This find extends the presence of East Eurasian lineages in Neolithic Europe from the Carpathian Mountains to the northern shores of the Black Sea and provides the first genetic account of Neolithic mtDNA lineages from the NPR.     

Genetic characteristics and migration history of a bronze culture population in the West Liao-River valley revealed by ancient DNA

In order to study the genetic characteristics of the Lower Xiajiadian culture (LXC) population, a main bronze culture branch in northern China dated 4500-3500 years ago, two uniparentally inherited markers, mitochondrial DNA and Y-chromosome single-nucleotide polymorphisms (Y-SNPs), were analyzed on 14 human remains excavated from the Dadianzi site. The 14 sequences, which contained 13 haplotypes, were assigned to 9 haplogroups, and Y-SNP typing of 5 male individuals assigned them to haplogroups N (M231) and O3 (M122). The results indicate that the LXC population mainly included people carrying haplogroups from northern Asia who had lived in this region since the Neolithic period, as well as genetic evidence of immigration from the Central Plain. Later in the Bronze Age, part of the population migrated to the south away from a cooler climate, which ultimately influenced the gene pool in the Central Plain. Thus, climate change is an important factor, which drove the population migration during the Bronze Age in northern China. Based on these results, the local genetic continuity did not seem to be affected by outward migration, although more data are needed especially from other ancient populations to determine the influence of return migration on genetic continuity.     

High-throughput sequencing of complete human mtDNA genomes from the Caucasus and West Asia: high diversity and demographic inferences

To investigate the demographic history of human populations from the Caucasus and surrounding regions, we used high-throughput sequencing to generate 147 complete mtDNA genome sequences from random samples of individuals from three groups from the Caucasus (Armenians, Azeri and Georgians), and one group each from Iran and Turkey. Overall diversity is very high, with 144 different sequences that fall into 97 different haplogroups found among the 147 individuals. Bayesian skyline plots (BSPs) of population size change through time show a population expansion around 40–50 kya, followed by a constant population size, and then another expansion around 15–18 kya for the groups from the Caucasus and Iran. The BSP for Turkey differs the most from the others, with an increase from 35 to 50 kya followed by a prolonged period of constant population size, and no indication of a second period of growth. An approximate Bayesian computation approach was used to estimate divergence times between each pair of populations; the oldest divergence times were between Turkey and the other four groups from the South Caucasus and Iran (∼400–600 generations), while the divergence time of the three Caucasus groups from each other was comparable to their divergence time from Iran (average of ∼360 generations). These results illustrate the value of random sampling of complete mtDNA genome sequences that can be obtained with high-throughput sequencing platforms.     

Mitochondrial super-haplogroup U diversity in Serbians

Abstract

Background: Available mitochondrial (mtDNA) data demonstrate genetic differentiation among South Slavs inhabiting the Balkan Peninsula. However, their resolution is insufficient to elucidate the female-specific aspects of the genetic history of South Slavs, including the genetic impact of various migrations which were rather common within the Balkans, a region having a turbulent demographic history.

Aim: The aim was to thoroughly study complete mitogenomes of Serbians, a population linking westward and eastward South Slavs.

Subjects and methods: Forty-six predominantly Serbian super-haplogroup U complete mitogenomes were analysed phylogenetically against ～4000 available complete mtDNAs of modern and ancient Western Eurasians.

Results: Serbians share a number of U mtDNA lineages with Southern, Eastern-Central and North-Western Europeans. Putative Balkan-specific lineages (e.g. U1a1c2, U4c1b1, U5b3j, K1a4l and K1a13a1) and lineages shared among Serbians (South Slavs) and West and East Slavs were detected (e.g. U2e1b1, U2e2a1d, U4a2a, U4a2c, U4a2g1, U4d2b and U5b1a1).

Conclusion: The exceptional diversity of maternal lineages found in Serbians may be associated with the genetic impact of both autochthonous pre-Slavic Balkan populations whose mtDNA gene pool was affected by migrations of various populations over time (e.g. Bronze Age pastoralists) and Slavic and Germanic newcomers in the early Middle Ages.     

In the heartland of Eurasia: the multilocus genetic landscape of Central Asian populations

Located in the Eurasian heartland, Central Asia has played a major role in both the early spread of modern humans out of Africa and the more recent settlements of differentiated populations across Eurasia. A detailed knowledge of the peopling in this vast region would therefore greatly improve our understanding of range expansions, colonizations and recurrent migrations, including the impact of the historical expansion of eastern nomadic groups that occurred in Central Asia. However, despite its presumable importance, little is known about the level and the distribution of genetic variation in this region. We genotyped 26 Indo-Iranian- and Turkic-speaking populations, belonging to six different ethnic groups, at 27 autosomal microsatellite loci. The analysis of genetic variation reveals that Central Asian diversity is mainly shaped by linguistic affiliation, with Turkic-speaking populations forming a cluster more closely related to East-Asian populations and Indo-Iranian speakers forming a cluster closer to Western Eurasians. The scattered position of Uzbeks across Turkic- and Indo-Iranian-speaking populations may reflect their origins from the union of different tribes. We propose that the complex genetic landscape of Central Asian populations results from the movements of eastern, Turkic-speaking groups during historical times, into a long-lasting group of settled populations, which may be represented nowadays by Tajiks and Turkmen. Contrary to what is generally thought, our results suggest that the recurrent expansions of eastern nomadic groups did not result in the complete replacement of local populations, but rather into partial admixture.     

Admixture, migrations, and dispersals in Central Asia: evidence from maternal DNA lineages

Mitochondrial DNA (mtDNA) lineages of 232 individuals from 12 Central Asian populations were sequenced for both control region hypervariable segments, and additional informative sites in the coding region were also determined. Most of the mtDNA lineages belong to branches of the haplogroups with an eastern Eurasian (A, B, C, D, F, G, Y, and M haplogroups) or a western Eurasian (HV, JT, UK, I, W, and N haplogroups) origin, with a small fraction of Indian M lineages. This suggests that the extant genetic variation found in Central Asia is the result of admixture of already differentiated populations from eastern and western Eurasia. Nonetheless, two groups of lineages, D4c and G2a, seem to have expanded from Central Asia and might have their Y-chromosome counterpart in lineages belonging to haplotype P(xR1a). The present results suggest that the mtDNA found out of Africa might be the result of a maturation phase, presumably in the Middle East or eastern Africa, that led to haplogroups M and N, and subsequently expanded into Eurasia, yielding a geographically structured group of external branches of these two haplogroups in western and eastern Eurasia, Central Asia being a contact zone between two differentiated groups of peoples.     

Mitochondrial DNA sequence diversity in two groups of Italian Veneto speakers from Veneto

Although frequencies of mitochondrial DNA (mtDNA) haplogroups in the different European populations are rather homogenous, there are a few European populations or linguistic isolates that show different mtDNA haplogroup distributions; examples are the Saami and Ladin speakers from the eastern Italian Alps.
MtDNA sequence diversity was analysed from subjects from two villages in Veneto. The first, Posina, is situated in the Venetian Alps near Vicenza. The second, Barco di Pravisdomini is a village on the plains near Venice. In spite of their common Veneto dialect, the two group populations have not preserved a genetic homogeneity; particularly, they show differences in T and J haplogroups frequencies. MtDNA diversity in these two groups seems to depend more on their geographic situation.     

Mitochondrial DNA analysis reveals diverse histories of tribal populations from India

We analyzed 370 bp of the first hypervariable region of the mitochondrial DNA (mtDNA) control region in 752 individuals from 17 tribal and four nontribal groups from the Indian subcontinent, to address questions concerning the origins, genetic structure and relationships of these groups. Southern Indian tribes showed reduced diversity and large genetic distances, both among themselves and when compared with other groups, and no signal of prehistoric demographic expansions. These results probably reflect enhanced genetic drift because of small population sizes and/or bottlenecks in these groups. By contrast, northern groups exhibited more diversity and signals of prehistoric demographic expansions. Phylogenetic analyses revealed that southern and northern groups (except northeastern ones) have related mtDNA sequences albeit at different frequencies, further supporting the larger impact of drift on the genetic structure of southern groups. The Indian mtDNA gene pool appears to be more closely related to the east Eurasian gene pool (including central, east and southeast Asian populations) than the west Eurasian one (including European and Caucasian populations). Within India, northeastern tribes are quite distinct from other groups; they are more closely related to east Asians than to other Indians. This is consistent with linguistic evidence in that these populations speak Tibeto-Burman languages of east Asian origin. Otherwise, analyses of molecular variance suggested that caste and tribal groups are genetically similar with respect to mtDNA variation.     

Afghanistan from a Y-chromosome perspective

Central Asia has served as a corridor for human migrations providing trading routes since ancient times. It has functioned as a conduit connecting Europe and the Middle East with South Asia and far Eastern civilizations. Therefore, the study of populations in this region is essential for a comprehensive understanding of early human dispersal on the Eurasian continent. Although Y- chromosome distributions in Central Asia have been widely surveyed, present-day Afghanistan remains poorly characterized genetically. The present study addresses this lacuna by analyzing 190 Pathan males from Afghanistan using high-resolution Y-chromosome binary markers. In addition, haplotype diversity for its most common lineages (haplogroups R1a1a*-M198 and L3-M357) was estimated using a set of 15 Y-specific STR loci. The observed haplogroup distribution suggests some degree of genetic isolation of the northern population, likely due to the Hindu Kush mountain range separating it from the southern Afghans who have had greater contact with neighboring Pathans from Pakistan and migrations from the Indian subcontinent. Our study demonstrates genetic similarities between Pathans from Afghanistan and Pakistan, both of which are characterized by the predominance of haplogroup R1a1a*-M198 (>50%) and the sharing of the same modal haplotype. Furthermore, the high frequencies of R1a1a-M198 and the presence of G2c-M377 chromosomes in Pathans might represent phylogenetic signals from Khazars, a common link between Pathans and Ashkenazi groups, whereas the absence of E1b1b1a2-V13 lineage does not support their professed Greek ancestry.     

Rapid coastal spread of First Americans: novel insights from South America's Southern Cone mitochondrial genomes

It is now widely agreed that the Native American founders originated from a Beringian source population ~15-18 thousand years ago (kya) and rapidly populated all of the New World, probably mainly following the Pacific coastal route. However, details about the migration into the Americas and the routes pursued on the continent still remain unresolved, despite numerous genetic, archaeological, and linguistic investigations. To examine the pioneering peopling phase of the South American continent, we screened literature and mtDNA databases and identified two novel mitochondrial DNA (mtDNA) clades, here named D1g and D1j, within the pan-American haplogroup D1. They both show overall rare occurrences but local high frequencies, and are essentially restricted to populations from the Southern Cone of South America (Chile and Argentina). We selected and completely sequenced 43 D1g and D1j mtDNA genomes applying highest quality standards. Molecular and phylogeographic analyses revealed extensive variation within each of the two clades and possibly distinct dispersal patterns. Their age estimates agree with the dating of the earliest archaeological sites in South America and indicate that the Paleo-Indian spread along the entire longitude of the American double continent might have taken even <2000 yr. This study confirms that major sampling and sequencing efforts are mandatory for uncovering all of the most basal variation in the Native American mtDNA haplogroups and for clarification of Paleo-Indian migrations, by targeting, if possible, both the general mixed population of national states and autochthonous Native American groups, especially in South America.     

A comprehensive review of HVS-I mitochondrial DNA variation of 19 Iranian populations

Iran is located along the Central Asian corridor, a natural artery that has served as a cross-continental route since the first anatomically modern human populations migrated out of Africa. We compiled and reanalyzed the HVS-I (hypervariable segment-I) of 3840 mitochondrial DNA (mtDNA) sequences from 19 Iranian populations and from 26 groups from adjacent countries to give a comprehensive review of the maternal genetic variation and investigate the impact of historical events and cultural factors on the maternal genetic structure of modern Iranians. We conclude that Iranians have a high level of genetic diversity. Thirty-six haplogroups were observed in Iran's populations, and most of them belong to widespread West-Eurasian haplogroups, such as H, HV, J, N, T, and U. In contrast, the predominant haplogroups observed in most of the adjacent countries studied here are H, M, D, R, U, and C haplogroups. Using principal component analysis, clustering, and genetic distance-based calculations, we estimated moderate genetic relationships between Iranian and other Eurasian groups. Further, analyses of molecular variance and comparing geographic and genetic structures indicate that mtDNA HVS-I sequence diversity does not exhibit any sharp geographic structure in the country. Barring a few from some culturally distinct and naturally separated minorities, most Iranian populations have a homogenous maternal genetic structure.     

Genetic features of ancient West Siberian people of the Middle Ages, revealed by mitochondrial DNA haplogroup analysis

In order to investigate the genetic features of ancient West Siberian people of the Middle Ages, we studied ancient DNA from bone remains excavated from two archeological sites in West Siberia: Saigatinsky 6 (eighth to eleventh centuries) and Zeleny Yar (thirteenth century). Polymerase chain reaction amplification and nucleotide sequencing of mitochondrial DNA (mtDNA) succeeded for 9 of 67 specimens examined, and the sequences were assigned to mtDNA haplogroups B4, C4, G2, H and U. This distribution pattern of mtDNA haplogroups in medieval West Siberian people was similar to those previously reported in modern populations living in West Siberia, such as the Mansi, Ket and Nganasan. Exact tests of population differentiation showed no significant differences between the medieval people and modern populations in West Siberia. The findings suggest that some medieval West Siberian people analyzed in the present study are included in direct ancestral lineages of modern populations native to West Siberia.     

Data from complete mtDNA sequencing of Tunisian centenarians: Testing haplogroup association and the “golden mean” to longevity

Since the mitochondrial theory of ageing was proposed, mitochondrial DNA (mtDNA) diversity has been largely studied in old people, however complete genomes are still rare, being limited to Japanese and UK/US samples. In this work, we evaluated possible longevity associated polymorphisms/haplogroups in an African population, from Tunisia, by performing complete mtDNA sequencing. This population has a mixed Eurasian/sub-Saharan mtDNA gene pool, which could potentially facilitate the evaluation of association for sub-Saharan lineages. Sub-Saharan haplogroups were shown to be significantly less represented in centenarians (9.5%) than in controls (54.5%), but it is not possible to rule out an influence of population structure, which is high in these populations. No recurrent polymorphism were more frequent in centenarians than in controls, and although the Tunisian centenarians presented less synonymous and replacement polymorphisms than controls, this difference was not statistically significant. So far, it does not seem that centenarians have significantly less mildly deleterious substitutions, not only in Tunisia but also in Japanese and UK/US samples, as tested here, not favouring a “golden mean” to longevity.     

Genetic evidence for an origin of the Armenians from Bronze Age mixing of multiple populations

The Armenians are a culturally isolated population who historically inhabited a region in the Near East bounded by the Mediterranean and Black seas and the Caucasus, but remain under-represented in genetic studies and have a complex history including a major geographic displacement during World War I. Here, we analyse genome-wide variation in 173 Armenians and compare them with 78 other worldwide populations. We find that Armenians form a distinctive cluster linking the Near East, Europe, and the Caucasus. We show that Armenian diversity can be explained by several mixtures of Eurasian populations that occurred between ~3000 and ~2000 bce, a period characterized by major population migrations after the domestication of the horse, appearance of chariots, and the rise of advanced civilizations in the Near East. However, genetic signals of population mixture cease after ~1200 bce when Bronze Age civilizations in the Eastern Mediterranean world suddenly and violently collapsed. Armenians have since remained isolated and genetic structure within the population developed ~500 years ago when Armenia was divided between the Ottomans and the Safavid Empire in Iran. Finally, we show that Armenians have higher genetic affinity to Neolithic Europeans than other present-day Near Easterners, and that 29% of Armenian ancestry may originate from an ancestral population that is best represented by Neolithic Europeans.     

Review of Croatian genetic heritage as revealed by mitochondrial DNA and Y chromosomal lineages

The aim of this review is to summarize the existing data collected in high-resolution phylogenetic studies of mitochondrial DNA and Y chromosome variation in mainland and insular Croatian populations. Mitochondrial DNA polymorphisms were explored in 721 individuals by sequencing mtDNA HVS-1 region and screening a selection of 24 restriction fragment length polymorphisms (RFLPs), diagnostic for main Eurasian mtDNA haplogroups. Whereas Y chromosome variation was analyzed in 451 men by using 19 single nucleotide polymorphism (SNP)/indel and 8 short tandem repeat (STR) loci. The phylogeography of mtDNA and Y chromosome variants of Croatians can be adequately explained within typical European maternal and paternal genetic landscape, with the exception of mtDNA haplogroup F and Y-chromosomal haplogroup P* which indicate a connection to Asian populations. Similar to other European and Near Eastern populations, the most frequent mtDNA haplogroups in Croatians were H (41.1%), U5 (10.3%), and J (9.7%). The most frequent Y chromosomal haplogroups in Croatians, I-P37 (41.7%) and R1a-SRY1532 (25%), as well as the observed structuring of Y chromosomal variance reveal a clearly evident Slavic component in the paternal gene pool of contemporary Croatian men. Even though each population and groups of populations are well characterized by maternal and paternal haplogroup distribution, it is important to keep in mind that linking phylogeography of various haplogroups with known historic and prehistoric scenarios should be cautiously performed.     

Human Y chromosome haplogroup R-V88: a paternal genetic record of early mid Holocene trans-Saharan connections and the spread of Chadic languages

Although human Y chromosomes belonging to haplogroup R1b are quite rare in Africa, being found mainly in Asia and Europe, a group of chromosomes within the paragroup R-P25^* are found concentrated in the central-western part of the African continent, where they can be detected at frequencies as high as 95%. Phylogenetic evidence and coalescence time estimates suggest that R-P25^* chromosomes (or their phylogenetic ancestor) may have been carried to Africa by an Asia-to-Africa back migration in prehistoric times. Here, we describe six new mutations that define the relationships among the African R-P25^* Y chromosomes and between these African chromosomes and earlier reported R-P25 Eurasian sub-lineages. The incorporation of these new mutations into a phylogeny of the R1b haplogroup led to the identification of a new clade (R1b1a or R-V88) encompassing all the African R-P25^* and about half of the few European/west Asian R-P25^* chromosomes. A worldwide phylogeographic analysis of the R1b haplogroup provided strong support to the Asia-to-Africa back-migration hypothesis. The analysis of the distribution of the R-V88 haplogroup in >1800 males from 69 African populations revealed a striking genetic contiguity between the Chadic-speaking peoples from the central Sahel and several other Afroasiatic-speaking groups from North Africa. The R-V88 coalescence time was estimated at 9200–5600 kya, in the early mid Holocene. We suggest that R-V88 is a paternal genetic record of the proposed mid-Holocene migration of proto-Chadic Afroasiatic speakers through the Central Sahara into the Lake Chad Basin, and geomorphological evidence is consistent with this view.     

Analyses of the mitochondrial mutations in the Chinese patients with sporadic Creutzfeldt–Jakob disease

Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause a variety of chronic diseases in central nervous system (CNS). However, the role of mtDNA mutations in sporadic Creutzfeldt–Jakob disease (sCJD) has still been unknown. In this study, we comparatively analyzed complete mtDNA sequences of 31 Chinese sCJD patients and 32 controls. Using MITOMASTER and PhyloTree, we characterized 520 variants in sCJD patients and 507 variants in control by haplogroup and allele frequencies. We classified the mtDNAs into 40 sub-haplogroups of 5 haplogroups, most of them being Asian-specific haplogroups. Haplogroup U, an European-specific haplogroups mtDNA, was found only in sCJD. The analysis to control region (CR) revealed a 31% increase in the frequency of mtDNA CR mutations in sCJD versus controls. In functional elements of the mtDNA CR, six CR mutations were in conserved sequence blocks I (CSBI) in sCJD, while only one in control (P<0.05). More mutants in transfer ribonucleic acid-Leu (tRNA-Leu) were detected in sCJD. The frequencies of two synonymous amino-acid changes, m.11467A>G, p.(=) in NADH dehydrogenase subunit 4 (ND4) and m.12372G>A, p.(=) in NADH dehydrogenase subunit 5 (ND5), in sCJD patients were higher than that of controls. Our study, for the first time, screened the variations of mtDNA of Chinese sCJD patients and identified some potential disease-related mutations for further investigations.     

The Etruscan timeline: a recent Anatolian connection

The origin of the Etruscans (the present day Tuscany, Italy), one of the most enigmatic non-Indo-European civilizations, is under intense controversy. We found novel genetic evidences on the mitochondrial DNA (mtDNA) establishing a genetic link between Anatolia and the ancient Etruria. By way of complete mtDNA genome sequencing of a novel autochthonous Tuscan branch of haplogroup U7 (namely U7a2a), we have estimated an historical time frame for the arrival of Anatolian lineages to Tuscany ranging from 1.1±0.1 to 2.3±0.4 kya B.P.     

Linking the sub-Saharan and West Eurasian gene pools: maternal and paternal heritage of the Tuareg nomads from the African Sahel

The Tuareg presently live in the Sahara and the Sahel. Their ancestors are commonly believed to be the Garamantes of the Libyan Fezzan, ever since it was suggested by authors of antiquity. Biological evidence, based on classical genetic markers, however, indicates kinship with the Beja of Eastern Sudan. Our study of mitochondrial DNA (mtDNA) sequences and Y chromosome SNPs of three different southern Tuareg groups from Mali, Burkina Faso and the Republic of Niger reveals a West Eurasian-North African composition of their gene pool. The data show that certain genetic lineages could not have been introduced into this population earlier than ∼9000 years ago whereas local expansions establish a minimal date at around 3000 years ago. Some of the mtDNA haplogroups observed in the Tuareg population were involved in the post-Last Glacial Maximum human expansion from Iberian refugia towards both Europe and North Africa. Interestingly, no Near Eastern mtDNA lineages connected with the Neolithic expansion have been observed in our population sample. On the other hand, the Y chromosome SNPs data show that the paternal lineages can very probably be traced to the Near Eastern Neolithic demic expansion towards North Africa, a period that is otherwise concordant with the above-mentioned mtDNA expansion. The time frame for the migration of the Tuareg towards the African Sahel belt overlaps that of early Holocene climatic changes across the Sahara (from the optimal greening ∼10 000 YBP to the extant aridity beginning at ∼6000 YBP) and the migrations of other African nomadic peoples in the area.