Ancient mitochondrial diversity reveals population homogeneity in Neolithic Greece and identifies population dynamics along the Danubian expansion axis.

The aim of the study is to investigate mitochondrial diversity in Neolithic Greece and its relation to hunter-gatherers and farmers who populated the Danubian Neolithic expansion axis. We sequenced 42 mitochondrial palaeogenomes from Greece and analysed them together with European set of 328 mtDNA sequences dating from the Early to the Final Neolithic and 319 modern sequences. To test for population continuity through time in Greece, we use an original structured population continuity test that simulates DNA from different periods by explicitly considering the spatial and temporal dynamics of populations. We explore specific scenarios of the mode and tempo of the European Neolithic expansion along the Danubian axis applying spatially explicit simulations coupled with Approximate Bayesian Computation. We observe a striking genetic homogeneity for the maternal line throughout the Neolithic in Greece whereas population continuity is rejected between the Neolithic and present-day Greeks. Along the Danubian expansion axis, our best-fitting scenario supports a substantial decrease in mobility and an increasing local hunter-gatherer contribution to the gene-pool of farmers following the initial rapid Neolithic expansion. Οur original simulation approach models key demographic parameters rather than inferring them from fragmentary data leading to a better understanding of this important process in European prehistory.

The population genomics of archaeological transition in west Iberia: Investigation of ancient substructure using imputation and haplotype-based methods.

We analyse new genomic data (0.05-2.95x) from 14 ancient individuals from Portugal distributed from the Middle Neolithic (4200-3500 BC) to the Middle Bronze Age (1740-1430 BC) and impute genomewide diploid genotypes in these together with published ancient Eurasians. While discontinuity is evident in the transition to agriculture across the region, sensitive haplotype-based analyses suggest a significant degree of local hunter-gatherer contribution to later Iberian Neolithic populations. A more subtle genetic influx is also apparent in the Bronze Age, detectable from analyses including haplotype sharing with both ancient and modern genomes, D-statistics and Y-chromosome lineages. However, the limited nature of this introgression contrasts with the major Steppe migration turnovers within third Millennium northern Europe and echoes the survival of non-Indo-European language in Iberia. Changes in genomic estimates of individual height across Europe are also associated with these major cultural transitions, and ancestral components continue to correlate with modern differences in stature.

Instrumented hip joint replacements, femoral replacements and femoral fracture stabilizers.

This paper reviews instrumented hip joint replacements, instrumented femoral replacements and instrumented femoral fracture stabilizers. Examination of the evolution of such implants was carried out, including the detailed analysis of 16 architectures, designed by 8 research teams and implanted in 32 patients. Their power supply, measurement, communication, processing and actuation systems were reviewed, as were the tests carried out to evaluate their performance and safety. These instrumented implants were only designed to measure biomechanical and thermodynamic quantities in vivo, in order to use such data to conduct research projects and optimize rehabilitation processes. The most promising trend is to minimize aseptic loosening and/or infection following hip or femoral replacements or femoral stabilization procedures by using therapeutic actuators inside instrumented implants to apply controlled stimuli in the bone-implant interface.

Instrumented hip implants: electric supply systems.

Instrumented hip implants were proposed as a method to monitor and predict the biomechanical and thermal environment surrounding such implants. Nowadays, they are being developed as active implants with the ability to prevent failures by loosening. The generation of electric energy to power active mechanisms of instrumented hip implants remains a question. Instrumented implants cannot be implemented without effective electric power systems. This paper surveys the power supply systems of seventeen implant architectures already implanted in-vivo, namely from instrumented hip joint replacements and instrumented fracture stabilizers. Only inductive power links and batteries were used in-vivo to power the implants. The energy harvesting systems, which were already designed to power instrumented hip implants, were also analyzed focusing their potential to overcome the disadvantages of both inductive-based and battery-based power supply systems. From comparative and critical analyses of the methods to power instrumented implants, one can conclude that: inductive powering and batteries constrain the full operation of instrumented implants; motion-driven electromagnetic energy harvesting is a promising method to power instrumented passive and active hip implants.

Investigating European genetic history through computer simulations.

BACKGROUND/AIMS: The genetic diversity of Europeans has been shaped by various evolutionary forces including their demographic history. Genetic data can thus be used to draw inferences on the population history of Europe using appropriate statistical methods such as computer simulation, which constitutes a powerful tool to study complex models. METHODS: Here, we focus on spatially explicit simulation, a method which takes population movements over space and time into account. We present its main principles and then describe a series of studies using this approach that we consider as particularly significant in the context of European prehistory. RESULTS AND CONCLUSION: All simulation studies agree that ancient demographic events played a significant role in the establishment of the European gene pool; but while earlier works support a major genetic input from the Near East during the Neolithic transition, the most recent ones revalue positively the contribution of pre-Neolithic hunter-gatherers and suggest a possible impact of very ancient demographic events. This result of a substantial genetic continuity from pre-Neolithic times to the present challenges some recent studies analyzing ancient DNA. We discuss the possible reasons for this discrepancy and identify future lines of investigation in order to get a better understanding of European evolution.

Human neutral genetic variation and forensic STR data.

The forensic genetics field is generating extensive population data on polymorphism of short tandem repeats (STR) markers in globally distributed samples. In this study we explored and quantified the informative power of these datasets to address issues related to human evolution and diversity, by using two online resources: an allele frequency dataset representing 141 populations summing up to almost 26 thousand individuals; a genotype dataset consisting of 42 populations and more than 11 thousand individuals. We show that the genetic relationships between populations based on forensic STRs are best explained by geography, as observed when analysing other worldwide datasets generated specifically to study human diversity. However, the global level of genetic differentiation between populations (as measured by a fixation index) is about half the value estimated with those other datasets, which contain a much higher number of markers but much less individuals. We suggest that the main factor explaining this difference is an ascertainment bias in forensics data resulting from the choice of markers for individual identification. We show that this choice results in average low variance of heterozygosity across world regions, and hence in low differentiation among populations. Thus, the forensic genetic markers currently produced for the purpose of individual assignment and identification allow the detection of the patterns of neutral genetic structure that characterize the human population but they do underestimate the levels of this genetic structure compared to the datasets of STRs (or other kinds of markers) generated specifically to study the diversity of human populations.

Pleistocene-Holocene boundary in Southern Arabia from the perspective of human mtDNA variation.

It is now known that several population movements have taken place at different times throughout southern Arabian prehistory. One of the principal questions under debate is if the Early Holocene peopling of southern Arabia was mainly due to input from the Levant during the Pre-Pottery Neolithic B, to the expansion of an autochthonous population, or some combination of these demographic processes. Since previous genetic studies have not been able to include all parts of southern Arabia, we have helped fill this lacuna by collecting new population datasets from Oman (Dhofar) and Yemen (Al-Mahra and Bab el-Mandab). We identified several new haplotypes belonging to haplogroup R2 and generated its whole genome mtDNA tree with age estimates undertaken by different methods. R2, together with other considerably frequent southern Arabian mtDNA haplogroups (R0a, HV1, summing up more than 20% of the South Arabian gene pool) were used to infer the past effective population size through Bayesian skyline plots. These data indicate that the southern Arabian population underwent a large expansion already some 12 ka. A founder analysis of these haplogroups shows that this expansion is largely attributed to demographic input from the Near East. These results support thus the spread of a population coming from the north, but at a significantly earlier date than presently considered by archaeologists. Our data suggest that some of the mtDNA lineages found in southern Arabia have persisted in the region since the end of the Last Ice Age.

A "Copernican" reassessment of the human mitochondrial DNA tree from its root.

Mutational events along the human mtDNA phylogeny are traditionally identified relative to the revised Cambridge Reference Sequence, a contemporary European sequence published in 1981. This historical choice is a continuous source of inconsistencies, misinterpretations, and errors in medical, forensic, and population genetic studies. Here, after having refined the human mtDNA phylogeny to an unprecedented level by adding information from 8,216 modern mitogenomes, we propose switching the reference to a Reconstructed Sapiens Reference Sequence, which was identified by considering all available mitogenomes from Homo neanderthalensis. This "Copernican" reassessment of the human mtDNA tree from its deepest root should resolve previous problems and will have a substantial practical and educational influence on the scientific and public perception of human evolution by clarifying the core principles of common ancestry for extant descendants.

The Arabian cradle: mitochondrial relicts of the first steps along the southern route out of Africa.

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.

The Expansion of mtDNA Haplogroup L3 within and out of Africa.

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.

Population history of the Red Sea--genetic exchanges between the Arabian Peninsula and East Africa signaled in the mitochondrial DNA HV1 haplogroup.

Archaeological studies have revealed cultural connections between the two sides of the Red Sea dating to prehistory. The issue has still not been properly addressed, however, by archaeogenetics. We focus our attention here on the mitochondrial haplogroup HV1 that is present in both the Arabian Peninsula and East Africa. The internal variation of 38 complete mitochondrial DNA sequences (20 of them presented here for the first time) affiliated into this haplogroup testify to its emergence during the late glacial maximum, most probably in the Near East, with subsequent dispersion via population expansions when climatic conditions improved. Detailed phylogeography of HV1 sequences shows that more recent demographic upheavals likely contributed to their spread from West Arabia to East Africa, a finding concordant with archaeological records suggesting intensive maritime trade in the Red Sea from the sixth millennium BC onwards. Closer genetic exchanges are apparent between the Horn of Africa and Yemen, while Egyptian HV1 haplotypes seem to be more similar to the Near Eastern ones.

Internal diversification of mitochondrial haplogroup R0a reveals post-last glacial maximum demographic expansions in South Arabia.

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.

Population expansion in the North African late Pleistocene signalled by mitochondrial DNA haplogroup U6.

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.

The trans-Saharan slave trade - clues from interpolation analyses and high-resolution characterization of mitochondrial DNA lineages.

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.

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

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

A ß-glucosidase from Oenococcus oeni ATCC BAA-1163 with potential for aroma release in wine: Cloning and expression in E. coli.

Lactic acid bacteria (LAB) are responsible for olfactory changes in wine during malolactic fermentation (MLF). A side characteristic of MLF is the release of grape derived aroma compounds from their glycosylated precursors by ß-glycosidase activities of these bacteria. Apart from Oenococcus oeni, which is regarded as the most promising species for MLF, glycosidic activities have also been observed in wine related members of the genera Lactobacillus and Pediococcus. Nevertheless, information on the involved enzymes including their potential use in winemaking is limited. In this study we report that ß-glucosidases with similar protein sequences can be identified in the genomes of Lactobacillus brevis, O. oeni and Leuconostoc mesenteroides. TTG serves as start codon for the glucosidase gene of O. oeni. The ß-glucosidase of O. oeni ATCC BAA-1163 was expressed in E. coli and partially characterized. The enzyme displayed characteristics similar to ß-glucosidases isolated from L. brevis and L. mesenteroides. A pH optimum between 5.0 and 5.5, and a K(m) of 0.17 mmol L(-1 )pNP-ß-D-glucopyranoside were determined. A glycosyltransferase activity was observed in the presence of ethanol. The enzyme from O. oeni was capable to hydrolyze glycosides extracted from Muskat wine. This study also contains a report on glycosidase activities of several LAB species including Oenococcus kitaharae.