Naturally acquired antibodies from Beninese infants promote Plasmodium falciparum merozoite-phagocytosis by human blood leukocytes: implications for control of asymptomatic malaria infections.

BACKGROUND: Immunoglobulin G (IgG) antibodies are thought to play important roles in the protection against Plasmodium falciparum (P. falciparum) malaria. A longitudinal cohort study performed in the Southern part of Benin, identified a group of infants who were able to control asymptomatic malaria infections (CAIG). METHODS: IgG antibodies against distinct merozoite antigens were quantified in plasma from Beninese infants. Functionality of these antibodies was assessed by the merozoite-phagocytosis assay using THP-1 cells and primary neutrophils as effector cells. Gm allotypes were determined by a serological method of haemagglutination inhibition. RESULTS: Purified IgG from infants in CAIG promoted higher levels of merozoite-phagocytosis than did IgG from children who were unable to control asymptomatic infections (Ologit multivariate regression model, Coef. = 0.06, 95% CI 0.02;0.10, P = 0.002). High level of merozoite-phagocytosis activity was significantly associated with high levels of IgG against AMA1 (Coef. = 1.76, 95% CI 0.39;3.14, P = 0.012) and GLURP-R2 (Coef. = 12.24, 95% CI 1.35;23.12, P = 0.028). Moreover, infants of the G3m5,6,10,11,13,14,24 phenotype showed higher merozoite-phagocytosis activity (Generalized linear model multivariate regression, Coef. = 7.46, 95% CI 0.31;14.61, P = 0.041) than those presenting other G3m phenotypes. CONCLUSION: The results of the present study confirm the importance of antibodies to merozoite surface antigens in the control of asymptomatic malaria infection in Beninese infants. The study also demonstrated that G3m phenotypes impact the functional activity of IgG. This last point could have a considerable impact in the research of candidate vaccines against malaria parasites or other pathogens.

Predicting haplogroups using a versatile machine learning program (PredYMaLe) on a new mutationally balanced 32 Y-STR multiplex (CombYplex): Unlocking the full potential of the human STR mutation rate spectrum to estimate forensic parameters.

We developed a new mutationally well-balanced 32 Y-STR multiplex (CombYplex) together with a machine learning (ML) program PredYMaLe to assess the impact of STR mutability on haplogourp prediction, while respecting forensic community criteria (high DC/HD). We designed CombYplex around two sub-panels M1 and M2 characterized by average and high-mutation STR panels. Using these two sub-panels, we tested how our program PredYmale reacts to mutability when considering basal branches and, moving down, terminal branches. We tested first the discrimination capacity of CombYplex on 996 human samples using various forensic and statistical parameters and showed that its resolution is sufficient to separate haplogroup classes. In parallel, PredYMaLe was designed and used to test whether a ML approach can predict haplogroup classes from Y-STR profiles. Applied to our kit, SVM and Random Forest classifiers perform very well (average 97 %), better than Neural Network (average 91 %) and Bayesian methods (< 90 %). We observe heterogeneity in haplogroup assignation accuracy among classes, with most haplogroups having high prediction scores (99-100 %) and two (E1b1b and G) having lower scores (67 %). The small sample sizes of these classes explain the high tendency to misclassify the Y-profiles of these haplogroups; results were measurably improved as soon as more training data were added. We provide evidence that our ML approach is a robust method to accurately predict haplogroups when it is combined with a sufficient number of markers, well-balanced mutation rate Y-STR panels, and large ML training sets. Further research on confounding factors (such as CNV-STR or gene conversion) and ideal STR panels in regard to the branches analysed can be developed to help classifiers further optimize prediction scores.

Susceptibility to Plasmodium falciparum Malaria: Influence of Combined Polymorphisms of IgG3 Gm Allotypes and Fc Gamma Receptors IIA, IIIA, and IIIB.

The binding of immunoglobulin (Ig) to Fc gamma receptors (FcgR) at the immune cell surface is an important step to initiate immunological defense against malaria. However, polymorphisms in receptors and/or constant regions of the IgG heavy chains may modulate this binding. Here, we investigated whether polymorphisms located in FcgR and constant regions of the heavy chain of IgG are associated with susceptibility to P. falciparum malaria. For this purpose, a clinical and parasitological follow-up on malaria was conducted among 656 infants in southern Benin. G3m allotypes (from total IgG3) were determined by a serological method of hemagglutination inhibition. FcgRIIA 131R/H and FcgRIIIA 176F/V genotypes were determined using the TaqMan method and FcgRIIIB NA1/NA2 genotypes were assessed by polymerase chain reaction using allele-specific primers. Association analyses between the number of malaria infections during the follow-up and polymorphisms in IgG G3m allotypes and FcgR were studied independently by zero inflated binomial negative regression. The influence of combinations of G3m allotypes and FcgRIIA/FcgRIIIA/FcgRIIIB polymorphisms on the number of P. falciparum infections, and their potential interaction with environmental exposure to malaria was assessed by using the generalized multifactor dimensionality reduction (GMDR) method. Results showed that individual carriage of G3m24 single allotype and of G3m5,6,10,11,13,14,24 phenotype was independently associated with a high risk of malaria infection. A risk effect for G3m6 was observed only under high environmental exposure. FcgRIIIA 176VV single genotype and combined carriage of FcgRIIA 131RH/FcgRIIIA 176VV/FcgRIIIB NA1NA2, FcgRIIA 131HH/FcgRIIIA 176FF/FcgRIIIB NA1NA1, FcgRIIA 131HH/FcgRIIIA 176VV/FcgRIIIB NA2NA2 and FcgRIIA 131HH/FcgRIIIA 176VV/FcgRIIIB NA1NA2 genotypes were related to a high number of malaria infections. The risk was accentuated for FcgRIIIA 176VV when considering the influence of environmental exposure to malaria. Finally, the GMDR analysis including environmental exposure showed strengthened associations with a malaria risk when FcgRIIA/FcgRIIIA/FcgRIIIB genotypes were combined to G3m5,6,11,24 and G3m5,6,10,11,13,15,24 phenotypes or G3m10 and G3m13 single allotypes. Our results highlight the relevance of studying IgG heavy chain and FcgR polymorphisms, independently as well as in combination, in relation to the individual susceptibility to P. falciparum infection. The intensity of individual exposure to mosquito bites was demonstrated to impact the relationships found.

Human Genomic Diversity Where the Mediterranean Joins the Atlantic.

Throughout the past few years, a lively debate emerged about the timing and magnitude of the human migrations between the Iberian Peninsula and the Maghreb. Several pieces of evidence, including archaeological, anthropological, historical, and genetic data, have pointed to a complex and intermingled evolutionary history in the western Mediterranean area. To study to what extent connections across the Strait of Gibraltar and surrounding areas have shaped the present-day genomic diversity of its populations, we have performed a screening of 2.5 million single-nucleotide polymorphisms in 142 samples from southern Spain, southern Portugal, and Morocco. We built comprehensive data sets of the studied area and we implemented multistep bioinformatic approaches to assess population structure, demographic histories, and admixture dynamics. Both local and global ancestry inference showed an internal substructure in the Iberian Peninsula, mainly linked to a differential African ancestry. Western Iberia, from southern Portugal to Galicia, constituted an independent cluster within Iberia characterized by an enriched African genomic input. Migration time modeling showed recent historic dates for the admixture events occurring both in Iberia and in the North of Africa. However, an integrative vision of both paleogenomic and modern DNA data allowed us to detect chronological transitions and population turnovers that could be the result of transcontinental migrations dating back from Neolithic times. The present contribution aimed to fill the gaps in the modern human genomic record of a key geographic area, where the Mediterranean and the Atlantic come together.

A multivariate statistical approach for the estimation of the ethnic origin of unknown genetic profiles in forensic genetics.

DNA typing and genetic profile data interpretation are among the most relevant topics in forensic science; among other applications, genetic profile's capability to distinguish biogeographic information about population groups, subgroups and affiliations have been largely explored in the last decade. In fact, for investigative and intelligence purposes, it is extremely useful to identify subjects and estimate their biogeographic origins by examining the recovered DNA profiles from evidence on a crime scene. Current approaches for BiogeoGraphic Ancestry (BGA) estimation using STRs profiles are usually based on Bayesian methods, which quantify the evidence in terms of likelihood ratio, supporting or not the hypothesis that a certain profile belongs to a specific ethnic group. The present study provides an alternative approach to the likelihood ratio method that involves multivariate data analysis strategies for the estimation of multiple populations. Starting from the well-known NIST US autosomal STRs dataset involving African-American, Asian, and Caucasian individuals, and moving towards further and more geographically restricted populations (such as Northern Africans vs sub-Saharan Africans, Afghans vs Iraqis and Italians vs Romanians), powerful multivariate techniques such as Sparse and Logistic Principal Component Analysis (SL-PCA), Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) and Support Vector Machines (SVM) were employed and their discriminating power was also compared. Both sPLS-DA and SVM techniques provided robust classifications, yielding high sensitivity and specificity models capable of discriminating populations on ethnic basis. This application may represent a powerful and dynamic tool for law enforcement agencies whenever a standard autosomal STR profile is obtained from the biological evidence collected at a crime scene or recovered during mass-disaster and missing person investigations.

Paternal lineages in southern Iberia provide time frames for gene flow from mainland Europe and the Mediterranean world.

BACKGROUND: The geography of southern Iberia and an abundant archaeological record of human occupation are ideal conditions for a full understanding of scenarios of genetic history in the area. Recent advances in the phylogeography of Y-chromosome lineages offer the opportunity to set upper bounds for the appearance of different genetic components. AIM: To provide a global knowledge on the Y haplogroups observed in Andalusia with their Y microsatellite variation. Preferential attention is given to the vehement debate about the age, origin and expansion of R1b-M269 clade and sub-lineages. SUBJECT AND METHODS: Four hundred and fourteen male DNA samples from western and eastern autochthonous Andalusians were genotyped for a set of Y-SNPs and Y-STRs. Gene diversity, potential population genetic structures and coalescent times were assessed. RESULTS: Most of the analysed samples belong to the European haplogroup R1b1a1a2-M269, whereas haplogroups E, J, I, G and T show lower frequencies. A phylogenetic dissection of the R1b-M269 was performed and younger time frames than those previously reported in the literature were obtained for its sub-lineages. CONCLUSION: The particular Andalusian R1b-M269 assemblage confirms the shallow topology of the clade. Moreover, the sharing of lineages with the rest of Europe indicates the impact in Iberia of an amount of pre-existing diversity, with the possible exception of R1b-DF27. Lineages such as J2-M172 and G-M201 highlight the importance of maritime travels of early farmers who reached the Iberian Peninsula.

Rapidly mutating Y-STRs in rapidly expanding populations: Discrimination power of the Yfiler Plus multiplex in northern Africa.

The male-specific northern African genetic pool is characterised by a high frequency of the E-M81 haplogroup, which expanded in very recent times (2-3 kiloyears ago). As a consequence of their recent coalescence, E-M81 chromosomes often cannot be completely distinguished on the basis of their Y-STR profiles, unless rapidly-mutating Y-STRs (RM Y-STRs) are analysed. In this study, we used the Yfiler® Plus kit, which includes 7 RM Y-STRs and 20 standard Y-STR, to analyse 477 unrelated males coming from 11 northern African populations sampled from Morocco, Algeria, Libya and Egypt. The Y chromosomes were assigned to monophyletic lineages after the analysis of 72 stable biallelic polymorphisms and, as expected, we found a high proportion of E-M81 subjects (about 46%), with frequencies decreasing from west to east. We found low intra-population diversity indexes, in particular in the populations that experienced long-term isolation. The AMOVA analysis showed significant differences between the countries and between most of the 11 populations, with a rough differentiation between northwestern Africa and northeastern Africa, where the Egyptians Berbers from Siwa represented an outlier population. The comparison between the Yfiler® and the Yfiler® Plus network of the E-M81 Y chromosomes confirmed the high power of discrimination of the latter kit, thanks to higher variability of the RM Y-STRs: indeed, the number of chromosomes sharing the same haplotype was drastically reduced from 201 to 81 and limited, in the latter case, to subjects from the same population.

Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance.

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.

The peopling of the last Green Sahara revealed by high-coverage resequencing of trans-Saharan patrilineages.

BACKGROUND: Little is known about the peopling of the Sahara during the Holocene climatic optimum, when the desert was replaced by a fertile environment. RESULTS: In order to investigate the role of the last Green Sahara in the peopling of Africa, we deep-sequence the whole non-repetitive portion of the Y chromosome in 104 males selected as representative of haplogroups which are currently found to the north and to the south of the Sahara. We identify 5,966 mutations, from which we extract 142 informative markers then genotyped in about 8,000 subjects from 145 African, Eurasian and African American populations. We find that the coalescence age of the trans-Saharan haplogroups dates back to the last Green Sahara, while most northern African or sub-Saharan clades expanded locally in the subsequent arid phase. CONCLUSIONS: Our findings suggest that the Green Sahara promoted human movements and demographic expansions, possibly linked to the adoption of pastoralism. Comparing our results with previously reported genome-wide data, we also find evidence for a sex-biased sub-Saharan contribution to northern Africans, suggesting that historical events such as the trans-Saharan slave trade mainly contributed to the mtDNA and autosomal gene pool, whereas the northern African paternal gene pool was mainly shaped by more ancient events.

Reconstructing an African haploid genome from the 18th century.

A genome is a mosaic of chromosome fragments from ancestors who existed some arbitrary number of generations earlier. Here, we reconstruct the genome of Hans Jonatan (HJ), born in the Caribbean in 1784 to an enslaved African mother and European father. HJ migrated to Iceland in 1802, married and had two children. We genotyped 182 of his 788 descendants using single-nucleotide polymorphism (SNP) chips and whole-genome sequenced (WGS) 20 of them. Using these data, we reconstructed 38% of HJ's maternal genome and inferred that his mother was from the region spanned by Benin, Nigeria and Cameroon.

Genome-wide Ancestry and Demographic History of African-Descendant Maroon Communities from French Guiana and Suriname.

The transatlantic slave trade was the largest forced migration in world history. However, the origins of the enslaved Africans and their admixture dynamics remain unclear. To investigate the demographic history of African-descendant Marron populations, we generated genome-wide data (4.3 million markers) from 107 individuals from three African-descendant populations in South America, as well as 124 individuals from six west African populations. Throughout the Americas, thousands of enslaved Africans managed to escape captivity and establish lasting communities, such as the Noir Marron. We find that this population has the highest proportion of African ancestry (∼98%) of any African-descendant population analyzed to date, presumably because of centuries of genetic isolation. By contrast, African-descendant populations in Brazil and Colombia harbor substantially more European and Native American ancestry as a result of their complex admixture histories. Using ancestry tract-length analysis, we detect different dates for the European admixture events in the African-Colombian (1749 CE; confidence interval [CI]: 1737-1764) and African-Brazilian (1796 CE; CI: 1789-1804) populations in our dataset, consistent with the historically attested earlier influx of Africans into Colombia. Furthermore, we find evidence for sex-specific admixture patterns, resulting from predominantly European paternal gene flow. Finally, we detect strong genetic links between the African-descendant populations and specific source populations in Africa on the basis of haplotype sharing patterns. Although the Noir Marron and African-Colombians show stronger affinities with African populations from the Bight of Benin and the Gold Coast, the African-Brazilian population from Rio de Janeiro has greater genetic affinity with Bantu-speaking populations from the Bight of Biafra and west central Africa.

Dispersals and genetic adaptation of Bantu-speaking populations in Africa and North America.

Bantu languages are spoken by about 310 million Africans, yet the genetic history of Bantu-speaking populations remains largely unexplored. We generated genomic data for 1318 individuals from 35 populations in western central Africa, where Bantu languages originated. We found that early Bantu speakers first moved southward, through the equatorial rainforest, before spreading toward eastern and southern Africa. We also found that genetic adaptation of Bantu speakers was facilitated by admixture with local populations, particularly for the HLA and LCT loci. Finally, we identified a major contribution of western central African Bantu speakers to the ancestry of African Americans, whose genomes present no strong signals of natural selection. Together, these results highlight the contribution of Bantu-speaking peoples to the complex genetic history of Africans and African Americans.

Human Immunoglobulin Heavy Gamma Chain Polymorphisms: Molecular Confirmation Of Proteomic Assessment.

Immunoglobulin G (IgG) proteins are known for the huge diversity of the variable domains of their heavy and light chains, aimed at protecting each individual against foreign antigens. The IgG also harbor specific polymorphism concentrated in the CH2 and CH3-CHS constant regions located on the Fc fragment of their heavy chains. But this individual particularity relies only on a few amino acids among which some could make accurate sequence determination a challenge for mass spectrometry-based techniques.The purpose of the study was to bring a molecular validation of proteomic results by the sequencing of encoding DNA fragments. It was performed using ten individual samples (DNA and sera) selected on the basis of their Gm (gamma marker) allotype polymorphism in order to cover the main immunoglobulin heavy gamma (IGHG) gene diversity. Gm allotypes, reflecting part of this diversity, were determined by a serological method. On its side, the IGH locus comprises four functional IGHG genes totalizing 34 alleles and encoding the four IgG subclasses. The genomic study focused on the nucleotide polymorphism of the CH2 and CH3-CHS exons and of the intron. Despite strong sequence identity, four pairs of specific gene amplification primers could be designed. Additional primers were identified to perform the subsequent sequencing. The nucleotide sequences obtained were first assigned to a specific IGHG gene, and then IGHG alleles were deduced using a home-made decision tree reading of the nucleotide sequences. IGHG amino acid (AA) alleles were determined by mass spectrometry. Identical results were found at 95% between alleles identified by proteomics and those deduced from genomics. These results validate the proteomic approach which could be used for diagnostic purposes, namely for a mother-and-child differential IGHG detection in a context of suspicion of congenital infection.

Genetic Variations in the TP53 Pathway in Native Americans Strongly Suggest Adaptation to the High Altitudes of the Andes.

The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway (TP53, rs1042522; MDM2, rs2279744; MDM4, rs1563828; USP7, rs1529916; and LIF, rs929271) were studied in a total of 282 individuals belonging to Quechua, Aymara, Chivay, Cabanaconde, Yanke, Taquile, Amantani, Anapia, Uros, Guarani Ñandeva, and Guarani Kaiowá populations, characterized as Native American or as having a high level (> 90%) of Native American ancestry. In addition, published data pertaining to 100 persons from five other Native American populations (Surui, Karitiana, Maya, Pima, and Piapoco) were analyzed. The populations were classified as living in high altitude (≥ 2,500 m) or in lowlands (< 2,500 m). Our analyses revealed that alleles USP7-G, LIF-T, and MDM2-T showed significant evidence that they were selected for in relation to harsh environmental variables related to high altitudes. Our results show for the first time that alleles of classical TP53 network genes have been evolutionary co-opted for the successful human colonization of the Andes.

Genetic population study of Y-chromosome markers in Benin and Ivory Coast ethnic groups.

Ninety-six single nucleotide polymorphisms (SNPs) and seventeen short tandem repeat (STRs) were investigated on the Y-chromosome of 288 unrelated healthy individuals from populations in Benin (Bariba, Yoruba, and Fon) and the Ivory Coast (Ahizi and Yacouba). We performed a multidimensional scaling analysis based on FST and RST genetic distances using a large extensive database of sub-Saharan African populations. There is more genetic homogeneity in Ivory Coast populations compared with populations from Benin. Notably, the Beninese Yoruba are significantly differentiated from neighbouring groups, but also from the Yoruba from Nigeria (FST>0.05; P<0.01). The Y-chromosome dataset presented here provides new valuable data to understand the complex genetic diversity and human male demographic events in West Africa.

Phylogeographic Refinement and Large Scale Genotyping of Human Y Chromosome Haplogroup E Provide New Insights into the Dispersal of Early Pastoralists in the African Continent.

Haplogroup E, defined by mutation M40, is the most common human Y chromosome clade within Africa. To increase the level of resolution of haplogroup E, we disclosed the phylogenetic relationships among 729 mutations found in 33 haplogroup DE Y-chromosomes sequenced at high coverage in previous studies. Additionally, we dissected the E-M35 subclade by genotyping 62 informative markers in 5,222 samples from 118 worldwide populations. The phylogeny of haplogroup E showed novel features compared with the previous topology, including a new basal dichotomy. Within haplogroup E-M35, we resolved all the previously known polytomies and assigned all the E-M35* chromosomes to five new different clades, all belonging to a newly identified subhaplogroup (E-V1515), which accounts for almost half of the E-M35 chromosomes from the Horn of Africa. Moreover, using a Bayesian phylogeographic analysis and a single nucleotide polymorphism-based approach we localized and dated the origin of this new lineage in the northern part of the Horn, about 12 ka. Time frames, phylogenetic structuring, and sociogeographic distribution of E-V1515 and its subclades are consistent with a multistep demic spread of pastoralism within north-eastern Africa and its subsequent diffusion to subequatorial areas. In addition, our results increase the discriminative power of the E-M35 haplogroup for use in forensic genetics through the identification of new ancestry-informative markers.

Surnames and Y-chromosomal markers reveal low relationships in Southern Spain.

A sample of 416 males from western and eastern Andalusia has been jointly analyzed for surnames and Y-chromosome haplogroups and haplotypes. The observed number of different surnames was 222 (353 when the second surname of the Spanish system of naming is considered). The great majority of recorded surnames have a Castilian-Leonese origin, while Catalan or Basque surnames have not been found. A few Arab-related surnames appear but none discernible of Sephardic-Jewish descent. Low correlation among surnames with different population frequencies and Y-chromosome markers, at different levels of genetic resolution, has been observed in Andalusia. This finding could be explained mainly by the very low rate of monophyletic surnames because of the historical process of surname ascription and the resulting high frequencies of the most common Spanish surnames. The introduction of surnames in Spain during the Middle Ages coincided with Reconquest of the territories under Islamic rule, and Muslims and Jews progressively adopted the present male line surname system. Sampled surnames and Y-chromosome lineages fit well a power-law distribution and observed isonymy is very close to that of the general population. Besides, our data and results show that the reliability of the isonymy method should be questioned because of the high rate of polyphyletic surnames, even in small geographic regions and autochthonous populations. Random isonymy would be consistently dependent of the most common surname frequencies in the population.

Determined about sex: sex-testing in 45 primate species using a 2Y/1X sex-typing assay.

Sex-testing using molecular genetic technique is routinely used in the fields of forensics, population genetics and conservation biology. However, none of the assay used so far allows a non-ambiguous and successful sex determination for human and non-human primate species. The most widely used method, AMELY/X, and its alternatives suffer from a set of drawbacks in humans and can rarely be used in New World primate species. Here, we designed a new sex-typing assay using a multiplexed PCR amplification of UTX and UTY-homologous loci and combined male-specific SRY locus. This method was successfully tested on 1048 samples, including 82 non-human primates from 45 Anthropoidea and Lemuriformes species and 966 human samples from 24 populations (Africans, Europeans, and South Americans). This sex-typing method is applicable across all primate species tested from Hominoidea to Indriidae, and also on various populations with different background origins; it represents a robust and cheap sex-typing assay to be used both by the anthropologist and primatologist communities.

Immunoglobulin genes in Andalusia (Spain). Genetic diversity in the Mediterranean space.

Andalusia is the most densely populated region of Spain since ancient times, and has a rich history of contacts across the Mediterranean. Earlier studies have underlined the relatively high frequency of the Sub-Saharan GM 1,17 5* haplotype in western Andalusia (Huelva province, n=252) and neighbouring Atlantic regions. Here, we provide novel data on GM/KM markers in eastern Andalusians (n=195) from Granada province, where African GM*1,17 5* frequency is relatively high (0.044). The most frequent GM haplotypes in Andalusia parallel the most common in Europe. Altogether, these data allow us to gain insight into the genetic diversity of southern Iberia. Additionally, we assess population structure by comparing our Iberian samples with 41 Mediterranean populations. GM haplotype variation across the Mediterranean reflects intense and complex interactions between North Africans and South Europeans along human history, highlighting that African influence over the Iberian Peninsula does not follow an isotropic pattern.

Ancient human genomes suggest three ancestral populations for present-day Europeans.

We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.