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Field epidemiology and viral sequencing provide a comprehensive characterization of transmission chains and allow a better identification of superspreading events. However, very few examples have been presented to date during the COVID-19 pandemic. We studied the first COVID-19 cluster detected in Portugal (59 individuals involved amongst extended family and work environments), following the return of four related individuals from work trips to Italy. The first patient to introduce the virus would be misidentified following the traditional field inquiry alone, as shown by the viral sequencing in isolates from 23 individuals. The results also pointed out family, and not work environment, as the primary mode of transmission. This work was funded by Portuguese Foundation for Science and Technology (FCT; Research4COVID19 projects 198_596862267, 617_613735895, 186_596855206). FCT also financed the PhD grant to NP (SFRH/BD/136299/2018) and post-doc grant to VF (SFRH/BPD/114927/2016).

The Arabian Peninsula is strategic for investigations centered on the early structuring of modern humans in the wake of the out-of-Africa migration. Despite its poor climatic conditions for the recovery of ancient human DNA evidence, the availability of both genomic data from neighboring ancient specimens and informative statistical tools allow modeling the ancestry of local modern populations. We applied this approach to a data set of 741,000 variants screened in 291 Arabians and 78 Iranians, and obtained insightful evidence. The west-east axis was a strong forcer of population structure in the Peninsula, and, more importantly, there were clear continuums throughout time linking western Arabia with the Levant, and eastern Arabia with Iran and the Caucasus. Eastern Arabians also displayed the highest levels of the basal Eurasian lineage of all tested modern-day populations, a signal that was maintained even after correcting for a possible bias due to a recent sub-Saharan African input in their genomes. Not surprisingly, eastern Arabians were also the ones with highest similarity with Iberomaurusians, who were, so far, the best proxy for the basal Eurasians amongst the known ancient specimens. The basal Eurasian lineage is the signature of ancient non-Africans who diverged from the common European-eastern Asian pool before 50,000 years ago, prior to the later interbred with Neanderthals. Our results appear to indicate that the exposed basin of the Arabo-Persian Gulf was the possible home of basal Eurasians, a scenario to be further investigated by searching ancient Arabian human specimens.

A few molecularly proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding coronavirus disease 2019 (COVID-19) case in a 17-year-old Portuguese female. She had two hospitalizations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. The viral genome was sequenced in seven serial samples and in the diagnostic sample from her infected mother. A human genome-wide array (&gt, 900 K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. The patient had co-infection by two SARS-CoV-2 lineages, which were affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with the patient’s mother), but nine days later, the 20B lineage had 3% frequency, and two months later, the 20B lineage had 100% frequency. The 900 K profiles confirmed the identity of the patient in the serial samples, and they allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. The early-on dynamic co-infection may have contributed to the severity of COVID-19 in this otherwise healthy young patient, and to her prolonged SARS-CoV-2 shedding profile.

ObjectivesA few molecularly proven SARS-CoV-2 cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding COVID-19 case in a teenager Portuguese female. She had two hospitalisations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days.MethodsThe viral genome was sequenced in seven serial samples and in the diagnostic sample from an infected close relative. A human genome-wide array (>900K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples.ResultsThe patient had co-infection by two SARS-CoV-2 strains, affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with a cohabitating relative), but nine days later the 20B lineage had 3% frequency, and two months later the 20B lineage had 100% frequency. The 900K profiles confirmed the identity of the patient in the serial samples, and allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort.ConclusionsThe early-on dynamic co-infection was the probable cause for the severity of COVID-19 in this otherwise healthy young patient, and for her prolonged SARS-CoV-2 shedding profile.

O conceito de resiliência familiar menciona que uma família se pode tornar mais resiliente através de experiências vividas no decorrer do ciclo vital, em interação com o meio envolvente. Em todas as famílias são vivenciadas situações de stress e momentos de crise, como a descoberta da doença crónica. O convívio familiar com a doença crónica pode tornar-se desgastante para os membros da família, principalmente para o cuidador informal. Torna-se essencial os enfermeiros de saúde familiar adotarem cuidados que visem ao aumento da resiliência familiar, potenciando a família a ultrapassar a crise, readaptando-se. Este estudo teve como objetivos: conhecer o perfil de resiliência familiar de uma amostra de cuidadores informais em doentes com doença crónica; identificar quais os recursos comunidade que promovem a resiliência da família; avaliar a relação entre os fatores sociodemográficos familiares e a resiliência familiar. Desenvolveu-se um estudo quantitativo, transversal, de caracter descritivo, numa amostra não probabilística por conveniência, constituída por 26 cuidadores informais de utentes institucionalizados nas Unidades de Cuidados Continuados, pertencentes ao grupo Naturidade. Foi aplicado um questionário relativo à caraterização sociodemográfica e um questionário que avalia a resiliência familiar, denominado de Family Resilience Assessment Scale, adaptado para a população portuguesa. Verificou-se que a amostra apresentava um elevado nível de resiliência familiar (M=170,23; DP=14,49). Apesar 92,3% dos questionados referirem não recorrerem a ninguém perante a dificuldade, os mesmos assinalam em 65,4% recorrer aos vizinhos, em 57,7% aos sistemas de saúde, em 50% a outros familiares e em 96,2% à igreja. Foi verificado que não existe correlação estatisticamente significativa entre a resiliência familiar e a idade do inquirido (p>0,005). Da mesma forma, foi possível observar que não existe correlação estatisticamente significativa entre a resiliência familiar e o género da amostra (p>0,005).

Prevalence of many complex diseases, including dengue disease, is not even across the world. Dengue is endemic in several overpopulated urban centers in poor Asian and American countries, representing a risk to two-thirds of the human population. High-throughput genomic screenings and new algorithms of admixture mapping are allowing confirming that ancestry plays a major role in dengue disease. Allele and haplotype candidate frequencies display high heterogeneity between population groups, especially in comparison with Africans. Genetic risk evaluation testifies African ancestry protection against the more severe forms of the disease, most probably due to natural selection of protective variants. European genetic predisposition is identical to the Asian for severer forms, but lower for mild dengue fever.

Background Today, African pastoralists are found mainly in the Sahel/Savannah belt spanning 6,000 km from west to east, flanked by the Sahara to the north and tropical rainforests to the south. The most significant group among them are the Fulani who not only keep cattle breeds of possible West Eurasian ancestry, but form themselves a gene pool containing some paternally and maternally-transmitted West Eurasian haplogroups. Materials and Methods We generated complete sequences for 33 mitogenomes belonging to haplogroups H1 and U5 (23 and 10, respectively), and genotyped 16 STRs in 65 Y chromosomes belonging to haplogroup R1b-V88. Results We show that age estimates of the maternal lineage H1cb1, occurring almost exclusively in the Fulani, point to the time when the first cattle herders settled the Sahel/Savannah belt. Similar age estimates were obtained for paternal lineage R1b-V88, which occurs today in the Fulani but also in other, mostly pastoral populations. Maternal clade U5b1b1b, reported earlier in the Berbers, shows a shallower age, suggesting another possibly independent input into the Sahelian pastoralist gene pool. Conclusions Despite the fact that animal domestication originated in the Near East ∼ 10 ka, and that it was from there that animals such as sheep, goats as well as cattle were introduced into Northeast Africa soon thereafter, contemporary cattle keepers in the Sahel/Savannah belt show uniparental genetic affinities that suggest the possibility of an ancient contact with an additional ancestral population of western Mediterranean ancestry.

The Austronesian dispersal across the Indonesian Ocean to Madagascar and the Comoros has been well documented, but in an unexplained anomaly, few to no traces have been found of the Austronesian expansion in East Africa or the Arabian Peninsula. To revisit this peculiarity, we surveyed the Western Indian Ocean rim populations to identify potential Austronesian genetic ancestry. We generated full mitochondrial DNA genomes and genome-wide genotyping data for these individuals and compared them with the Banjar, the Indonesian source population of the westward Austronesian dispersal. We find strong support for Asian genetic contributions to maternal lineages and autosomal variation in modern day Somalia and Yemen. Surprisingly, this input reveals two apparently different geographic origins and timings of admixture for the Austronesian contact; one at a very early phase (likely associated with the early Austronesian dispersals), and a later movement dating to the end of nineteenth century. These Austronesian gene flows come, respectively, from Madagascar and directly from an unidentified location in Island Southeast Asia. This result reveals a far more complex dynamic of Austronesian dispersals through the Western Indian Ocean than has previously been understood and suggests that Austronesian movements within the Indian Ocean may have been part of a lengthy process, probably continuing well into the modern era., GenoToul bioinformatics facility of Genopole Toulouse Midi-Pyrénées, France. We thank the CNRGH production team for genotyping data generation. This work was supported by French Ministry of Research grant ANR-14-CE31-0013-01 (OCEOADAPTO) to F.-X.R, the French Ministry of Foreign and European Affairs (French Archaeological Mission in Borneo (MAFBO) to F.-X.R.), and the French Embassy in Indonesia through its Cultural and Cooperation Services (Institut Français en Indonésie); a fellowship from the Alexander von Humboldt Foundation to M.P.C.; funding from the Max Planck Society to M.S.; and grants from COMPETE 2020 and a Fundação para a Ciência e a Tecnologia-funded project (POCI-01-0145-FEDER-016609) to V.F

Due to its long genetic evolutionary history, Africans exhibit more genetic variation than any other population in the world. Their genetic diversity further lends itself to subdivisions of Africans into groups of individuals with a genetic similarity of varying degrees of granularity. It remains challenging to detect fine-scale structure in a computationally efficient and meaningful way. In this paper, we present a proof-of-concept of a novel fine-scale population structure detection tool with Western African samples. These samples consist of 1396 individuals from 25 ethnic groups (two groups are African American descendants). The strategy is based on a recently developed tool called IPCAPS. IPCAPS, or Iterative Pruning to CApture Population Structure, is a genetic divisive clustering strategy that enhances iterative pruning PCA, is robust to outliers and does not require a priori computation of haplotypes. Our strategy identified in total 12 groups and 6 groups were revealed as fine-scale structure detected in the samples from Cameroon, Gambia, Mali, Southwest USA, and Barbados. Our finding helped to explain evolutionary processes in the analyzed West African samples and raise awareness for fine-scale structure resolution when conducting genome-wide association and interaction studies. Electronic supplementary material The online version of this article (10.1007/s00439-019-02069-7) contains supplementary material, which is available to authorized users.

International audience; Population genetics theory predicted that rare frequent markers would be the main contributors for heritability of complex diseases, but meta-analyses of genome-wide association studies are revealing otherwise common markers, present in all population groups, as the identified candidate genes. In this work, we applied a population-genetics informed meta-analysis to 10 markers located in seven genes said to be associated with dengue fever disease. Seven markers (in PLCE1, CD32, CD209, OAS1 and OAS3 genes) have high-frequency and the other three (in MICB and TNFA genes) have intermediate frequency. Most of these markers have high discriminatory power between population groups, but their frequencies follow the rules of genetic drift, and seem to have not been under strong selective pressure. There was a good agreement in directional consistency across trans-ethnic association signals, in East Asian and Latin American cohorts, with heterogeneity generated by randomness between studies and especially by low sample sizes. This led to confirm the following significant associations: with DF, odds ratio of 0.67 for TNFA-rs1800629-A; with DHF, 0.82 for CD32-rs1801274-G; with DSS, 0.55 for OAS3-rs2285933-G, 0.80 for PLCE1-rs2274223-G and 1.32 for MICB-rs3132468-C. The overall genetic risks confirmed sub-Saharan African populations and descendants as the best protected against the severer forms of the disease, while Southeast and Northeast Asians are the least protected ones. European and close neighbours are the best protected against dengue fever, while, again, Southeast and Northeast Asians are the least protected ones. These risk scores provide important predictive information for the largely na\"ive European and North American regions, as well as for Africa where misdiagnosis with other hemorrhagic diseases is of concern.

The physiopathology of autoimmune hepatitis (AIH) is complex and still not fully elucidated. The genes localized outside the histocompatibility complex involved in regulation and signal transduction of the immune system SH2B3, TGFβ1, STAT4 and PTPN22 could be associated to the susceptibility and hepatocyte lysis mechanism of this lethal autoimmune disorder. Patients and methods We investigated four polymorphic sites in SH2B3 (rs3184504), TGFβ1 (rs1800471), STAT4 (rs7574865) and PTPN22 (rs2476601) in 45 AIH patients and 150 healthy controls from Tunisia using real-time PCR. Results Significant associations were found for SH2B3 T allele (OR = 1.861; p = 0.015, pc = 0.366) and PTPN22 A allele (OR = 7.070; p = 0.026; pc = 1.00) and AIH with opposite homozygous being protective against the disease (CC genotype with OR = 0.420, p = 0.025; GG genotype with OR = 0.136, p = 0.025, respectively). No statistically significant associations were found for the TGFβ1 and STAT4 polymorphisms with AIH susceptibility. Conclusion Our work enlarges information on non-HLA genes that are associated with AIH by focusing in a region of the world that was poorly molecularly characterized for this disease.

Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS., Author summary Dengue fever is endemic in tropical and subtropical areas of East Asia and America, but globalization and climate changes are introducing vector and virus to the naïve regions of Europe and North America. In this work we conducted a statistically robust, coupled association-admixture test in two dengue cohorts from Thailand (classical dengue fever, DF, and dengue shock syndrome, DSS) and a published Vietnamese (DSS only) cohort. We identified new candidate genes associated with DF risk and confirmed known gene family association with DSS risk. In DF, phosphatase control is crucial, including through binding to viral proteins, as we showed for PPP2R5E protein co-localization with DENV1 and DENV2-NS5 proteins within liver cells and differential cellular localizations along time. In DSS, cytokine dynamics, inflammation and activation of vascular endothelium cells are dominant features. The particular genetic risk conferred by these genes indicates that Southeast and Northeast Asians are highly susceptible to both phenotypes, while Africans are best protected against DSS, and Europeans best protected against DF but the most susceptible against DSS.

At the dawn of the second millennium, the expansion of the Indian Ocean trading network aligned with the emergence of an outward-oriented community along the East African coast to create a cosmopolitan cultural and trading zone known as the Swahili Corridor. On the basis of analyses of new genome-wide genotyping data and uniparental data in 276 individuals from coastal Kenya and the Comoros islands, along with large-scale genetic datasets from the Indian Ocean rim, we reconstruct historical population dynamics to show that the Swahili Corridor is largely an eastern Bantu genetic continuum. Limited gene flows from the Middle East can be seen in Swahili and Comorian populations at dates corresponding to historically documented contacts. However, the main admixture event in southern insular populations, particularly Comorian and Malagasy groups, occurred with individuals from Island Southeast Asia as early as the 8th century, reflecting an earlier dispersal from this region. Remarkably, our results support recent archaeological and linguistic evidence-based suggestions that the Comoros archipelago was the earliest location of contact between Austronesian and African populations in the Swahili Corridor. We acknowledge support from the GenoToul bioinformatics facility of Genopole Toulouse Midi-Pyre´ne´es, France. This research was supported by French Ministry of Research grant ANR-14-CE31-0013-01 (OCEOADAPTO) to F.-X.R, a Rutherford Fellowship from the Royal Society of New Zealand (RDF-10- MAU-001), a fellowship from the Alexander von Humboldt Foundation to M.P.C., and grants from COMPETE 2020 and a Fundac¸a˜o para a Cieˆncia e a Tecnologia-funded project (POCI-01-0145-FEDER-016609) to V.F. We thank Kamil Merito for his help collecting East African samples. We thank all the local Swahili and Comorian communities who participated in this study.

We conducted the first systematic omics study of the oncocytic phenotype in 488 papillary thyroid carcinomas (PTC) from The Cancer Genome Atlas. Oncocytic phenotype is secondary to PTC, being unrelated to several pathologic scores. The nuclear genome had low impact on this phenotype (except in specific copy number variation), which was mostly driven by the significant accumulation of mitochondrial DNA non-synonymous and frameshift mutations at high heteroplasmy levels. Energy and mitochondrial-related pathways were significantly enriched in oncocytic tumors that also displayed increased levels of expression for genes involved in autophagy and fusion of mitochondria. Our in vitro tests confirmed that autophagy is increased and functional while mitophagy is decreased in these tumors.

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. This work was funded by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche (ANR) grant AGRHUM (ANR-14-CE02-0003-01), and the “Histoire du Génome des Populations Humaines Gabonaises” project (Institut Pasteur/Republic of Gabon).

Human mitochondrial DNA haplogroup U is among the initial maternal founders in Southwest Asia and Europe and one that best indicates matrilineal genetic continuity between late Pleistocene hunter-gatherer groups and present-day populations of Europe. While most haplogroup U subclades are older than 30 thousand years, the comparatively recent coalescence time of the extant variation of haplogroup U7 (∼16-19 thousand years ago) suggests that its current distribution is the consequence of more recent dispersal events, despite its wide geographical range across Europe, the Near East and South Asia. Here we report 267 new U7 mitogenomes that - analysed alongside 100 published ones - enable us to discern at least two distinct temporal phases of dispersal, both of which most likely emanated from the Near East. The earlier one began prior to the Holocene (∼11.5 thousand years ago) towards South Asia, while the later dispersal took place more recently towards Mediterranean Europe during the Neolithic (∼8 thousand years ago). These findings imply that the carriers of haplogroup U7 spread to South Asia and Europe before the suggested Bronze Age expansion of Indo-European languages from the Pontic-Caspian Steppe region., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Os grupos em situação de exclusão social estão sobrerrepresentados na população reclusa, sendo que as desigualdades económicas e sociais estão muitas vezes relacionadas com diferenças no acesso aos serviços de saúde. Como resultado, a população reclusa apresenta um nível de saúde significativamente inferior ao da população geral. Os profissionais de saúde que trabalham em contextos prisionais confrontam-se, assim, com uma série de dificuldades, ligadas não só a aspetos próprios do fenómeno da reclusão, como também a particularidades da própria população. No presente trabalho partimos da reflexão em torno de algumas questões relacionadas com a saúde em contexto prisional, chegando a um conjunto de medidas e princípios operativos. Prison population is overrepresented by social disadvantaged groups. These economic and social inequalities are often related to differences in access to health services. As a result, prison population has a lower level of health compared to general population. Health care providers must face a number of difficulties, which are not only linked to the characteristics of confinement, but also derived by individual characteristics. In this work, we start from a reflection on some issues related to health in the prison context, arriving at a set of measures and operating principles. Les groupes en situation d’exclusion sociale sont surreprésentés dans la population carcérale. Ces inégalités économiques et sociales sont souvent liées à des différences dans l’accès aux services de santé. En conséquence, la population carcérale présente un niveau de santé nettement inférieur à celui de la population en général. Le professionnel de santé travaillant en milieu carcéral est confronté avec un certain nombre de difficultés, liées non seulement aux caractéristiques du phénomène d’emprisonnement, mais également à des spécificités provenant de la population elle-même. Avec ce travail nous nous appuyons sur une réflexion autour de certaines questions liées à la santé en milieu carcéral, afin d’arriver à une série de démarches et principes opérationnels.

A high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (∼11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed., Contract grant sponsors: FCT, the Portuguese Foundation for Science and Technology (PTDC/IVC-ANT/4917/2012, SFRH/BD/78990/2011, and IF/01641/2013); FEDER, COMPETE, and FCT (FCOMP-01-0124-FEDER-029291, PEst-C/SAU/LA0003/2013, and PEst-OE/BIA/UI4050/2014); Luso American Foundation (FLAD).

At the crossroads between Africa and Eurasia, Arabia is necessarily a melting pot, its peoples enriched by successive gene flow over the generations. Estimating the timing and impact of these multiple migrations are important steps in reconstructing the key demographic events in the human history. However, current methods based on genome-wide information identify admixture events inefficiently, tending to estimate only the more recent ages, as here in the case of admixture events across the Red Sea (~8-37 generations for African input into Arabia, and 30-90 generations for "back-to-Africa" migrations). An mtDNA-based founder analysis, corroborated by detailed analysis of the whole-mtDNA genome, affords an alternative means by which to identify, date and quantify multiple migration events at greater time depths, across the full range of modern human history, albeit for the maternal line of descent only. In Arabia, this approach enables us to infer several major pulses of dispersal between the Near East and Arabia, most likely via the Gulf corridor. Although some relict lineages survive in Arabia from the time of the out-of-Africa dispersal, 60 ka, the major episodes in the peopling of the Peninsula took place from north to south in the Late Glacial and, to a lesser extent, the immediate post-glacial/Neolithic. Exchanges across the Red Sea were mainly due to the Arab slave trade and maritime dominance (from ~2.5 ka to very recent times), but had already begun by the early Holocene, fuelled by the establishment of maritime networks since ~8 ka. The main "back-to-Africa" migrations, again undetected by genome-wide dating analyses, occurred in the Late Glacial period for introductions into eastern Africa, whilst the Neolithic was more significant for migrations towards North Africa.

The origins of Ashkenazi Jews remain highly controversial. Like Judaism, mitochondrial DNA is passed along the maternal line. Its variation in the Ashkenazim is highly distinctive, with four major and numerous minor founders. However, due to their rarity in the general population, these founders have been difficult to trace to a source. Here we show that all four major founders, ~40% of Ashkenazi mtDNA variation, have ancestry in prehistoric Europe, rather than the Near East or Caucasus. Furthermore, most of the remaining minor founders share a similar deep European ancestry. Thus the great majority of Ashkenazi maternal lineages were not brought from the Levant, as commonly supposed, nor recruited in the Caucasus, as sometimes suggested, but assimilated within Europe. These results point to a significant role for the conversion of women in the formation of Ashkenazi communities, and provide the foundation for a detailed reconstruction of Ashkenazi genealogical history., Ashkenazi mitochondrial DNA variation has four major founders whose sources are difficult to trace due to the rarity of Ashkenazi Jews in the general population. Here, the authors provide evidence that all four major founders originated from Europe and provide a genealogical record of the Ashkenazi.

A major unanswered question regarding the dispersal of modern humans around the world concerns the geographical site of the first human steps outside of Africa. The "southern coastal route" model predicts that the early stages of the dispersal took place when people crossed the Red Sea to southern Arabia, but genetic evidence has hitherto been tenuous. We have addressed this question by analyzing the three minor west-Eurasian haplogroups, N1, N2, and X. These lineages branch directly from the first non-African founder node, the root of haplogroup N, and coalesce to the time of the first successful movement of modern humans out of Africa, ∼60 thousand years (ka) ago. We sequenced complete mtDNA genomes from 85 Southwest Asian samples carrying these haplogroups and compared them with a database of 300 European examples. The results show that these minor haplogroups have a relict distribution that suggests an ancient ancestry within the Arabian Peninsula, and they most likely spread from the Gulf Oasis region toward the Near East and Europe during the pluvial period 55-24 ka ago. This pattern suggests that Arabia was indeed the first staging post in the spread of modern humans around the world. FCT, the Portuguese Foundation for Science and Technology, supported this work through the research project PTDC/CS-ANT/113832/2009 and the personal grants to V.F. (SFRH/BD/61342/2009), N.M.S. (SFRH/BD/69119/2010), J.B.P. (SFRH/BD/45657/2008), M.D.C. (SFRH/BD/48372/2008), and P.S. (SFRH/BPD/64233/2009). We also thank the Leverhulme Trust (research project grant 10 105/D) and the DeLaszlo Foundation for financial support to P.S. The Instituto de Patologia e Imunologia Molecular da Universidade do Porto is an Associate Laboratory of the Portuguese Ministry of Science, Technology, and Higher Education and is partially supported by FCT.

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Although fossil remains show that anatomically modern humans dispersed out of Africa into the Near East ∼100 to 130 ka, genetic evidence from extant populations has suggested that non-Africans descend primarily from a single successful later migration. Within the human mitochondrial DNA (mtDNA) tree, haplogroup L3 encompasses not only many sub-Saharan Africans but also all ancient non-African lineages, and its age therefore provides an upper bound for the dispersal out of Africa. An analysis of 369 complete African L3 sequences places this maximum at ∼70 ka, virtually ruling out a successful exit before 74 ka, the date of the Toba volcanic supereruption in Sumatra. The similarity of the age of L3 to its two non-African daughter haplogroups, M and N, suggests that the same process was likely responsible for both the L3 expansion in Eastern Africa and the dispersal of a small group of modern humans out of Africa to settle the rest of the world. The timing of the expansion of L3 suggests a link to improved climatic conditions after ∼70 ka in Eastern and Central Africa rather than to symbolically mediated behavior, which evidently arose considerably earlier. The L3 mtDNA pool within Africa suggests a migration from Eastern Africa to Central Africa ∼60 to 35 ka and major migrations in the immediate postglacial again linked to climate. The largest population size increase seen in the L3 data is 3-4 ka in Central Africa, corresponding to Bantu expansions, leading diverse L3 lineages to spread into Eastern and Southern Africa in the last 3-2 ka. FCT, the Portuguese Foundation for Science and Technology, supported this work through the research project PTDC/ANT/66275/2006 and the personal grants to V.F. (SFRH/BD/61342/2009), J.B.P. (SFRH/BD/45657/2008), M.D.C. (SFRH/BD/48372/2008), N.M.S. (SFRH/BD/69119/2010), and P.S. (SFRH/BPD/64233/2009). P.S. also thanks the de Laszlo Foundation for financial support. The Ministry of Education of the Czech Republic also supported this work through the grant KONTAKT ME 917. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology, and Higher Education and is partially supported by FCT.

Widespread interest in the first successful Out of Africa dispersal of modern humans ∼60-80 thousand years ago via a southern migration route has overshadowed the study of later periods of South Arabian prehistory. In this work, we show that the post-Last Glacial Maximum period of the past 20,000 years, during which climatic conditions were becoming more hospitable, has been a significant time in the formation of the extant genetic composition and population structure of this region. This conclusion is supported by the internal diversification displayed in the highly resolved phylogenetic tree of 89 whole mitochondrial genomes (71 being newly presented here) for haplogroup R0a-the most frequent and widespread haplogroup in Arabia. Additionally, two geographically specific clades (R0a1a1a and R0a2f1) have been identified in non-Arabic speaking peoples such as the Soqotri and Mahri living in the southern part of the Arabian Peninsula where a past refugium was identified by independent archaeological studies. Estimates of time to the most recent common ancestor of these lineages match the earliest archaeological evidence for seafaring activity in the peninsula in the sixth millennium BC. This project was supported by the Fulbright-Masaryk Fellowship of V.C. at the Department of Anthropology, University of Florida, the Ministry of Education of the Czech Republic, Grant number: KONTAKT ME 917, the Council of American Overseas Research Centers, the American Institute for Yemeni Studies, and the Portuguese Fundação para a Ciência e a Tecnologia (PTDC/ANT/66275/2006) (L.P.), (Instituto de Patologia e Imunologia Molecular da Universidade do Porto is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by the Portuguese Foundation for Science and Technology, FCT). This research was also supported by a grant from the National Science Foundation to C.J.M. (BSR-0518530).

We analyzed the current status (as of the end of August 2008) of human mitochondrial genomes deposited in GenBank, amounting to 5140 complete or coding-region sequences, in order to present an overall picture of the diversity present in the mitochondrial DNA of the global human population. To perform this task, we developed mtDNA-GeneSyn, a computer tool that identifies and exhaustedly classifies the diversity present in large genetic data sets. The diversity observed in the 5140 human mitochondrial genomes was compared with all possible transitions and transversions from the standard human mitochondrial reference genome. This comparison showed that tRNA and rRNA secondary structures have a large effect in limiting the diversity of the human mitochondrial sequences, whereas for the protein-coding genes there is a bias toward less variation at the second codon positions. The analysis of the observed amino acid variations showed a tolerance of variations that convert between the amino acids V, I, A, M, and T. This defines a group of amino acids with similar chemical properties that can interconvert by a single transition. This work was financed by a project (PTDC/AFR/71422/2006) funded by FCT (Fundação para a Ciência e a Tecnologia). IPATIMUP is supported by Programa Operacional Ciência, Tecnologia e Inovação (POCTI) e Quadro Comunitário de Apoio III. The authors state that they have no conflicts of interest.

Background Chad Basin, lying within the bidirectional corridor of African Sahel, is one of the most populated places in Sub-Saharan Africa today. The origin of its settlement appears connected with Holocene climatic ameliorations (aquatic resources) that started ~10,000 years before present (YBP). Although both Nilo-Saharan and Niger-Congo language families are encountered here, the most diversified group is the Chadic branch belonging to the Afro-Asiatic language phylum. In this article, we investigate the proposed ancient migration of Chadic pastoralists from Eastern Africa based on linguistic data and test for genetic traces of this migration in extant Chadic speaking populations. Results We performed whole mitochondrial genome sequencing of 16 L3f haplotypes, focused on clade L3f3 that occurs almost exclusively in Chadic speaking people living in the Chad Basin. These data supported the reconstruction of a L3f phylogenetic tree and calculation of times to the most recent common ancestor for all internal clades. A date ~8,000 YBP was estimated for the L3f3 sub-haplogroup, which is in good agreement with the supposed migration of Chadic speaking pastoralists and their linguistic differentiation from other Afro-Asiatic groups of East Africa. As a whole, the Afro-Asiatic language family presents low population structure, as 92.4% of mtDNA variation is found within populations and only 3.4% of variation can be attributed to diversity among language branches. The Chadic speaking populations form a relatively homogenous cluster, exhibiting lower diversification than the other Afro-Asiatic branches (Berber, Semitic and Cushitic). Conclusion The results of our study support an East African origin of mitochondrial L3f3 clade that is present almost exclusively within Chadic speaking people living in Chad Basin. Whole genome sequence-based dates show that the ancestral haplogroup L3f must have emerged soon after the Out-of-Africa migration (around 57,100 ± 9,400 YBP), but the "Chadic" L3f3 clade has much less internal variation, suggesting an expansion during the Holocene period about 8,000 ± 2,500 YBP. This time period in the Chad Basin is known to have been particularly favourable for the expansion of pastoralists coming from northeastern Africa, as suggested by archaeological, linguistic and climatic data.

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. We thank all the sample donors, especially the centenarians. This work was financed by a project (PTDC/AFR/71422/2006) funded by FCT (Fundação para a Ciência e a Tecnologia). IPATIMUP is supported by Programa Operacional Ciência, Tecnologia e Inovação (POCTI) e Quadro Comunitario de Apoio III.

The Egyptian Western Desert lies on an important geographic intersection between Africa and Asia. Genetic diversity of this region has been shaped, in part, by climatic changes in the Late Pleistocene and Holocene epochs marked by oscillating humid and arid periods. We present here a whole genome analysis of mitochondrial DNA (mtDNA) and high-resolution molecular analysis of nonrecombining Y-chromosomal (NRY) gene pools of a demographically small but autochthonous population from the Egyptian Western Desert oasis el-Hayez. Notwithstanding signs of expected genetic drift, we still found clear genetic evidence of a strong Near Eastern input that can be dated into the Neolithic. This is revealed by high frequencies and high internal variability of several mtDNA lineages from haplogroup T. The whole genome sequencing strategy and molecular dating allowed us to detect the accumulation of local mtDNA diversity to 5,138 +/- 3,633 YBP. Similarly, theY-chromosome gene pool reveals high frequencies of the Near Eastern J1 and the North African E1b1b1b lineages, both generally known to have expanded within North Africa during the Neolithic. These results provide another piece of evidence of the relatively young population history of North Africa. Czech Science Foundation; Grant number: GA206/08/1587; Grant sponsor: Fundacao para a Ciencia e a Tecnologia (Programa Operacional Ciencia, Tecnologia e Inovacao–Quadro Comunitario de Apoio III); Grant number: PTDC/ANT/66275/2006; Grant sponsor: Ministry of Education, Youth and Sports; Grant number: 0048620802.

The first large-scale fine characterization of Tunisian H lineages clarifies that the post-Last glacial maximum expansion originating in Iberia not only led to the resettlement of Europe but also of North Africa. We found that 46% of 81 Tunisian H lineages subscreened for 1,580 bp in mtDNA coding region were affiliated with H1 and H3 subhaplogroups, which are known to have originated in Iberia. Although no signs of local expansion were detected, which would allow a clear dating of their introduction, the younger and less diverse Tunisian H1 and H3 lineages indicate Iberia as the radiating centre. Major contributions from historical migrations to this Iberian genetic imprint in Tunisia were ruled out by the mtDNA gene pool similarity between Berber/Arab/cosmopolitan samples and some "Andalusian" communities, settled by the descendents of the "Moors" who once lived in Iberia for 10 centuries (between 8th and 17th centuries), before being expelled to Tunisia. Fundacao para a Ciencia e a Tecnologia; Grant numbers: POCTI/ANT/45139/2002, PTDC/ANT/66275/2006, a BIPTDC/ANT/66275/2006, SFRH/BD/16518/2004; Grant sponsors: IPATIMUP (Programa Operacional Ciencia), Tecnologia e Inovacao (POCTI), Quadro Comunitario de Apoio III, GRICES (Gabinete de Relacoes Internacionais da Ciencia e do Ensino Superior), The Tunisian Ministry of Higher Education, Scientific Research and Technology.

A major effort must be put in East and sub-Saharan African mtDNA diversity characterisation for the construction of an informative database. We contribute 102 new HVRI+HVRII Sudanese sequences. As expected this sample is highly diverse, mainly constituted of unique haplotypes (2.07% random match probability for HVRI alone), 72.5% of which belong to sub-Saharan haplogroups.

Background\ud \ud The archaeology of North Africa remains enigmatic, with questions of population continuity versus discontinuity taking centre-stage. Debates have focused on population transitions between the bearers of the Middle Palaeolithic Aterian industry and the later Upper Palaeolithic populations of the Maghreb, as well as between the late Pleistocene and Holocene.\ud \ud Results\ud Improved resolution of the mitochondrial DNA (mtDNA) haplogroup U6 phylogeny, by the screening of 39 new complete sequences, has enabled us to infer a signal of moderate population expansion using Bayesian coalescent methods. To ascertain the time for this expansion, we applied both a mutation rate accounting for purifying selection and one with an internal calibration based on four approximate archaeological dates: the settlement of the Canary Islands, the settlement of Sardinia and its internal population re-expansion, and the split between haplogroups U5 and U6 around the time of the first modern human settlement of the Near East.\ud \ud Conclusions\ud \ud A Bayesian skyline plot placed the main expansion in the time frame of the Late Pleistocene, around 20 ka, and spatial smoothing techniques suggested that the most probable geographic region for this demographic event was to the west of North Africa. A comparison with U6's European sister clade, U5, revealed a stronger population expansion at around this time in Europe. Also in contrast with U5, a weak signal of a recent population expansion in the last 5,000 years was observed in North Africa, pointing to a moderate impact of the late Neolithic on the local population size of the southern Mediterranean coast.

Background A proportion of 1/4 to 1/2 of North African female pool is made of typical sub-Saharan lineages, in higher frequencies as geographic proximity to sub-Saharan Africa increases. The Sahara was a strong geographical barrier against gene flow, at least since 5,000 years ago, when desertification affected a larger region, but the Arab trans-Saharan slave trade could have facilitate enormously this migration of lineages. Till now, the genetic consequences of these forced trans-Saharan movements of people have not been ascertained. Results The distribution of the main L haplogroups in North Africa clearly reflects the known trans-Saharan slave routes: West is dominated by L1b, L2b, L2c, L2d, L3b and L3d; the Center by L3e and some L3f and L3w; the East by L0a, L3h, L3i, L3x and, in common with the Center, L3f and L3w; while, L2a is almost everywhere. Ages for the haplogroups observed in both sides of the Saharan desert testify the recent origin (holocenic) of these haplogroups in sub-Saharan Africa, claiming a recent introduction in North Africa, further strengthened by the no detection of local expansions. Conclusions The interpolation analyses and complete sequencing of present mtDNA sub-Saharan lineages observed in North Africa support the genetic impact of recent trans-Saharan migrations, namely the slave trade initiated by the Arab conquest of North Africa in the seventh century. Sub-Saharan people did not leave traces in the North African maternal gene pool for the time of its settlement, some 40,000 years ago.