Viola Grugni

Reconciling migration models to the Americas with the variation of North American native mitogenomes

In this study we evaluated migration models to the Americas by using the information contained in native mitochondrial genomes (mitogenomes) from North America. Molecular and phylogeographic analyses of B2a mitogenomes, which are absent in Eskimo–Aleut and northern Na-Dene speakers, revealed that this haplogroup arose in North America ∼11–13 ka from one of the founder Paleo-Indian B2 mitogenomes. In contrast, haplogroup A2a, which is typical of Eskimo–Aleuts and Na-Dene, but also present in the easternmost Siberian groups, originated only 4–7 ka in Alaska, led to the first Paleo-Eskimo settlement of northern Canada and Greenland, and contributed to the formation of the Na-Dene gene pool. However, mitogenomes also show that Amerindians from northern North America, without any distinction between Na-Dene and non–Na-Dene, were heavily affected by an additional and distinctive Beringian genetic input. In conclusion, most mtDNA variation (along the double-continent) stems from the first wave from Beringia, which followed the Pacific coastal route. This was accompanied or followed by a second inland migratory event, marked by haplogroups X2a and C4c, which affected all Amerindian groups of Northern North America. Much later, the ancestral A2a carriers spread from Alaska, undertaking both a westward migration to Asia and an eastward expansion into the circumpolar regions of Canada. Thus, the first American founders left the greatest genetic mark but the original maternal makeup of North American Natives was subsequently reshaped by additional streams of gene flow and local population dynamics, making a three-wave view too simplistic.

DISTINGUISHING THE CO-ANCESTRIES OF HAPLOGROUP G Y-CHROMOSOMES IN THE POPULATIONS OF EUROPE AND THE CAUCASUS

Haplogroup G, together with J2 clades, has been associated with the spread of agriculture, especially in the European context. However, interpretations based on simple haplogroup frequency clines do not recognize underlying patterns of genetic diversification. Although progress has been recently made in resolving the haplogroup G phylogeny, a comprehensive survey of the geographic distribution patterns of the significant sub-clades of this haplogroup has not been conducted yet. Here we present the haplogroup frequency distribution and STR variation of 16 informative G sub-clades by evaluating 1472 haplogroup G chromosomes belonging to 98 populations ranging from Europe to Pakistan. Although no basal G-M201* chromosomes were detected in our data set, the homeland of this haplogroup has been estimated to be somewhere nearby eastern Anatolia, Armenia or western Iran, the only areas characterized by the co-presence of deep basal branches as well as the occurrence of high sub-haplogroup diversity. The P303 SNP defines the most frequent and widespread G sub-haplogroup. However, its sub-clades have more localized distribution with the U1-defined branch largely restricted to Near/Middle Eastern and the Caucasus, whereas L497 lineages essentially occur in Europe where they likely originated. In contrast, the only U1 representative in Europe is the G-M527 lineage whose distribution pattern is consistent with regions of Greek colonization. No clinal patterns were detected suggesting that the distributions are rather indicative of isolation by distance and demographic complexities.

Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole.

Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure.

Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct populations.

Sociocultural Behavior, Sex-Biased Admixture, and Effective Population Sizes in Central African Pygmies and Non-Pygmies

Sociocultural phenomena, such as exogamy or phylopatry, can largely determine human sex-specific demography. In Central Africa, diverging patterns of sex-specific genetic variation have been observed between mobile hunter-gatherer Pygmies and sedentary agricultural non-Pygmies. However, their sex-specific demography remains largely unknown. Using population genetics and approximate Bayesian computation approaches, we inferred male and female effective population sizes, sex-specific migration, and admixture rates in 23 Central African Pygmy and non-Pygmy populations, genotyped for autosomal, X-linked, Y-linked, and mitochondrial markers. We found much larger effective population sizes and migration rates among non-Pygmy populations than among Pygmies, in agreement with the recent expansions and migrations of non-Pygmies and, conversely, the isolation and stationary demography of Pygmy groups. We found larger effective sizes and migration rates for males than for females for Pygmies, and vice versa for non-Pygmies. Thus, although most Pygmy populations have patrilocal customs, their sex-specific genetic patterns resemble those of matrilocal populations. In fact, our results are consistent with a lower prevalence of polygyny and patrilocality in Pygmies compared with non-Pygmies and a potential female transmission of reproductive success in Pygmies. Finally, Pygmy populations showed variable admixture levels with the non-Pygmies, with often much larger introgression from male than from female lineages. Social discrimination against Pygmies triggering complex movements of spouses in intermarriages can explain these male-biased admixture patterns in a patrilocal context. We show how gender-related sociocultural phenomena can determine highly variable sex-specific demography among populations, and how population genetic approaches contrasting chromosomal types allow inferring detailed human sex-specific demographic history.

The phylogenetic and geographic structure of Y-chromosome haplogroup R1a

R1a-M420 is one of the most widely spread Y-chromosome haplogroups; however, its substructure within Europe and Asia has remained poorly characterized. Using a panel of 16 244 male subjects from 126 populations sampled across Eurasia, we identified 2923 R1a-M420 Y-chromosomes and analyzed them to a highly granular phylogeographic resolution. Whole Y-chromosome sequence analysis of eight R1a and five R1b individuals suggests a divergence time of ∼25 000 (95% CI: 21 300–29 000) years ago and a coalescence time within R1a-M417 of ∼5800 (95% CI: 4800–6800) years. The spatial frequency distributions of R1a sub-haplogroups conclusively indicate two major groups, one found primarily in Europe and the other confined to Central and South Asia. Beyond the major European versus Asian dichotomy, we describe several younger sub-haplogroups. Based on spatial distributions and diversity patterns within the R1a-M420 clade, particularly rare basal branches detected primarily within Iran and eastern Turkey, we conclude that the initial episodes of haplogroup R1a diversification likely occurred in the vicinity of present-day Iran.

The First Peopling of South America: New Evidence from Y-Chromosome Haplogroup Q

Recent progress in the phylogenetic resolution of the Y-chromosome phylogeny permits the male demographic dynamics and migratory events that occurred in Central and Southern America after the initial human spread into the Americas to be investigated at the regional level. To delve further into this issue, we examined more than 400 Native American Y chromosomes (collected in the region ranging from Mexico to South America) belonging to haplogroup Q – virtually the only branch of the Y phylogeny observed in modern-day Amerindians of Central and South America – together with 27 from Mongolia and Kamchatka. Two main founding lineages, Q1a3a1a-M3 and Q1a3a1-L54(xM3), were detected along with novel sub-clades of younger age and more restricted geographic distributions. The first was also observed in Far East Asia while no Q1a3a1-L54(xM3) Y chromosome was found in Asia except the southern Siberian-specific sub-clade Q1a3a1c-L330. Our data not only confirm a southern Siberian origin of ancestral populations that gave rise to Paleo-Indians and the differentiation of both Native American Q founding lineages in Beringia, but support their concomitant arrival in Mesoamerica, where Mexico acted as recipient for the first wave of migration, followed by a rapid southward migration, along the Pacific coast, into the Andean region. Although Q1a3a1a-M3 and Q1a3a1-L54(xM3) display overlapping general distributions, they show different patterns of evolution in the Mexican plateau and the Andean area, which can be explained by local differentiations due to demographic events triggered by the introduction of agriculture and associated with the flourishing of the Great Empires.

In search of the genetic footprints of Sumerians: a survey of Y-chromosome and mtDNA variation in the Marsh Arabs of Iraq

BackgroundFor millennia, the southern part of the Mesopotamia has been a wetland region generated by the Tigris and Euphrates rivers before flowing into the Gulf. This area has been occupied by human communities since ancient times and the present-day inhabitants, the Marsh Arabs, are considered the population with the strongest link to ancient Sumerians. Popular tradition, however, considers the Marsh Arabs as a foreign group, of unknown origin, which arrived in the marshlands when the rearing of water buffalo was introduced to the region.ResultsTo shed some light on the paternal and maternal origin of this population, Y chromosome and mitochondrial DNA (mtDNA) variation was surveyed in 143 Marsh Arabs and in a large sample of Iraqi controls. Analyses of the haplogroups and sub-haplogroups observed in the Marsh Arabs revealed a prevalent autochthonous Middle Eastern component for both male and female gene pools, with weak South-West Asian and African contributions, more evident in mtDNA. A higher male than female homogeneity is characteristic of the Marsh Arab gene pool, likely due to a strong male genetic drift determined by socio-cultural factors (patrilocality, polygamy, unequal male and female migration rates).ConclusionsEvidence of genetic stratification ascribable to the Sumerian development was provided by the Y-chromosome data where the J1-Page08 branch reveals a local expansion, almost contemporary with the Sumerian City State period that characterized Southern Mesopotamia. On the other hand, a more ancient background shared with Northern Mesopotamia is revealed by the less represented Y-chromosome lineage J1-M267*. Overall our results indicate that the introduction of water buffalo breeding and rice farming, most likely from the Indian sub-continent, only marginally affected the gene pool of autochthonous people of the region. Furthermore, a prevalent Middle Eastern ancestry of the modern population of the marshes of southern Iraq implies that if the Marsh Arabs are descendants of the ancient Sumerians, also the Sumerians were most likely autochthonous and not of Indian or South Asian ancestry.

Mitogenomes from Two Uncommon Haplogroups Mark Late Glacial/Postglacial Expansions from the Near East and Neolithic Dispersals within Europe

The current human mitochondrial (mtDNA) phylogeny does not equally represent all human populations but is biased in favour of representatives originally from north and central Europe. This especially affects the phylogeny of some uncommon West Eurasian haplogroups, including I and W, whose southern European and Near Eastern components are very poorly represented, suggesting that extensive hidden phylogenetic substructure remains to be uncovered. This study expanded and re-analysed the available datasets of I and W complete mtDNA genomes, reaching a comprehensive 419 mitogenomes, and searched for precise correlations between the ages and geographical distributions of their numerous newly identified subclades with events of human dispersal which contributed to the genetic formation of modern Europeans. Our results showed that haplogroups I (within N1a1b) and W originated in the Near East during the Last Glacial Maximum or pre-warming period (the period of gradual warming between the end of the LGM, ∼19 ky ago, and the beginning of the first main warming phase, ∼15 ky ago) and, like the much more common haplogroups J and T, may have been involved in Late Glacial expansions starting from the Near East. Thus our data contribute to a better definition of the Late and postglacial re-peopling of Europe, providing further evidence for the scenario that major population expansions started after the Last Glacial Maximum but before Neolithic times, but also evidencing traces of diffusion events in several I and W subclades dating to the European Neolithic and restricted to Europe.

Phylogenetic applications of whole Y-chromosome sequences and the Near Eastern origin of Ashkenazi Levites

Previous Y-chromosome studies have demonstrated that Ashkenazi Levites, members of a paternally inherited Jewish priestly caste, display a distinctive founder event within R1a, the most prevalent Y-chromosome haplogroup in Eastern Europe. Here we report the analysis of 16 whole R1 sequences and show that a set of 19 unique nucleotide substitutions defines the Ashkenazi R1a lineage. While our survey of one of these, M582, in 2,834 R1a samples reveals its absence in 922 Eastern Europeans, we show it is present in all sampled R1a Ashkenazi Levites, as well as in 33.8% of other R1a Ashkenazi Jewish males and 5.9% of 303 R1a Near Eastern males, where it shows considerably higher diversity. Moreover, the M582 lineage also occurs at low frequencies in non-Ashkenazi Jewish populations. In contrast to the previously suggested Eastern European origin for Ashkenazi Levites, the current data are indicative of a geographic source of the Levite founder lineage in the Near East and its likely presence among pre-Diaspora Hebrews.