The Neolithic transition in Europe: archaeological models and genetic evidence

The major pattern in the European gene pool is a southeast-northwest frequency gradient of classic genetic markers such as blood groups, which population geneticists initially attributed to the demographic impact of Neolithic farmers dispersing from the Near East. Molecular genetics has enriched this picture, with analyses of mitochondrial DNA and the Y chromosome allowing a more detailed exploration of alternative models for the spread of the Neolithic into Europe. This paper considers a range of possible models in the light of the detailed information now emerging from genetic studies

Palaeogenomics: Mitogenomes and Migrations in Europe’s Past

The latest in a series of transformative studies of DNA from prehistoric Europeans focuses on mitochondrial DNA, bringing fresh surprises and filling in important details of the early stages of a European ancestry stretching back more than 40,000 years

Rectifying long-standing misconceptions about the p statistic for molecular dating

When divided by a given mutation rate, the ρ (rho) statistic provides a simple estimator of the age of a clade within a phylogenetic tree by averaging the number of mutations from each sample in the clade to its root. However, a long-standing critique of the use of ρ in genetic dating has been quite often cited. Here we show that the critique is unfounded. We demonstrate by a formal mathematical argument and illustrate with a simulation study that ρ estimates are unbiased and also that ρ and maximum likelihood estimates do not differ in any systematic fashion. We also demonstrate that the claim that the associated confidence intervals commonly estimate the uncertainty inappropriately is flawed since it relies on a means of calculating standard errors that is not used by any other researchers, whereas an established expression for the standard error is largely unproblematic. We conclude that ρ dating, alongside approaches such as maximum likelihood (ML) and Bayesian inference, remains a useful tool for genetic dating

A Genetic Perspective on African Prehistory

The various genetic systems (mitochondrial DNA, the Y chromosome and the genome-wide autosomes) indicate that Africa is the most genetically diverse continent in the world and the most likely place of origin for anatomically modern humans. However, where in Africa modern human arose and how the current genetic makeup within the continent was shaped is still open to debate. Here, we summarise the debate and focus especially on the maternally-inherited mitochondrial DNA (mtDNA) and a recently revised chronology for the African mtDNA tree. We discuss the possible origin of modern humans in southern, eastern or central Africa; the possibility of a migration from southern to eastern Africa more than 100 ka, carrying lineages within mtDNA haplogroup L0; the evidence for a climate-change-mediated population expansion in eastern Africa involving mtDNA haplogroup L3, leading to the “out-of-Africa” migration around 70–60 ka; the re-population of North Africa from the Near East around 40–30 ka suggested by mtDNA haplogroups U6 and M1; the evidence for population expansions and dispersals across the continent in the onset of the Holocene; and the impact of the Bantu dispersals in central, eastern and southern Africa within the last few millennia

Genetic Stratigraphy of Key Demographic Events in Arabia

The issue of admixture in human populations is normally addressed by genome-wide (GW) studies, and several approaches have been developed to date admixture events [1,2,3,4,5]. Admixed populations bear chromosomes with segments of DNA from all contributing source groups, the size of which decreases over successive generations until recombination renders them undetectably short. Several algorithms attempt to date admixture events by inferring the size of the nuclear ancestry segments, and these can work well when dating recent episodes in human history, such as the sub-Saharan African input into the New World [6], but they fail to detect several known episodes that took place at earlier times, such as the African input into Iberia [1] and genetic exchanges across the Red Sea [7]. Simulations with the suite of methods available at the ADMIXTOOLS package indicated that these methods could detect admixture events as early as 500 generation ago, but real data did not allow the tracing of such old events [8]. A recent improved algorithm, called GLOBETROTTER, has been used to tackle the detection of the co-occurrence of several mixture events by decomposing each chromosome into a series of haplotypic chunks and then analysing each chunk independently [3], but the problem of detecting ancient events remains. Its application to the systematic screening of worldwide admixture events was able to reveal around 100 events, but all occurring over only the past 4,000 years [3

Natural polymorphism in the thrombospondin-related adhesive protein of Plasmodium falciparum

We have developed a typing system using natural sequence variation in the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum. This method permits a haplotype to be assigned to any particular TRAP gene. We have applied this method to a hospital-based, case control-study in Mali. Previous sequence variation and conservation in TRAP has been confirmed. Particular TRAP haplotypes can be used as geographic hallmarks. Because of the high level of conflict between characters, we have examined the phylogenetic relationships between parasites using a network approach. Having received patient samples from urban and periurban areas of Bamako, the majority of haplotypes were closely related and distinct from TRAP sequences present in other continents. This suggests that the structure of TRAP can only tolerate a limited number of sequence variations to preserve its function but that this is sufficient to allow the parasite to evade the host's immune system until a long-lived immune response can be maintained. It may also reflect host genetics in that certain variants may escape the host immune response more efficiently than others. For vaccine design, sequences from the major regional variants may need to be considered in the production of effective subunit vaccines

Phylogeography of 27,000 SARS-CoV-2 genomes: Europe as the major source of the COVID-19 pandemic

Supplementary Material available at: https://www.mdpi.com/2076-2607/8/11/1678/s1The novel coronavirus SARS-CoV-2 emerged from a zoonotic transmission in China towards the end of 2019, rapidly leading to a global pandemic on a scale not seen for a century. In order to cast fresh light on the spread of the virus and on the effectiveness of the containment measures adopted globally, we used 26,869 SARS-CoV-2 genomes to build a phylogeny with 20,247 mutation events and adopted a phylogeographic approach. We confirmed that the phylogeny pinpoints China as the origin of the pandemic with major founders worldwide, mainly during January 2020. However, a single specific East Asian founder underwent massive radiation in Europe and became the main actor of the subsequent spread worldwide during March 2020. This lineage accounts for the great majority of cases detected globally and even spread back to the source in East Asia. Despite an East Asian source, therefore, the global pandemic was mainly fueled by its expansion across and out of Europe. It seems likely that travel bans established throughout the world in the second half of March helped to decrease the number of intercontinental exchanges, particularly from mainland China, but were less effective between Europe and North America where exchanges in both directions are visible up to April, long after bans were imposed.This work was supported by strategic project ICVS/3B’s (UID/Multi/50025), financed by Fundação para a Ciência e Tecnologia/MCTES through national funds (PIDDAC) to Teresa Rito. Martin B. Richards and Maria Pala received support from a Leverhulme Doctoral Scholarship program. This work was partially supported by project NORTE-01-0145-FEDER000009) by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by “Contrato-Programa” UIDB/04050/2020 funded by Portuguese national funds through the Fundação para a Ciência e Tecnologia to Pedro A. Soares

Climate change and postglacial human dispersals in southeast Asia

Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years. Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years--in particular, on a proposed Neolithic dispersal from China and Taiwan. Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized. We show that haplogroup E, an important component of mtDNA diversity in the region, evolved in situ over the last 35,000 years and expanded dramatically throughout ISEA around the beginning of the Holocene, at the time when the ancient continent of Sundaland was being broken up into the present-day archipelago by rising sea levels. It reached Taiwan and Near Oceania more recently, within the last approximately 8,000 years. This suggests that global warming and sea-level rises at the end of the Ice Age, 15,000-7,000 years ago, were the main forces shaping modern human diversity in the region

Molecular Anthropology in the genomic era

Molecular Anthropology is a relatively young field of research. In fact, less than 50 years have passed since the symposium ''Classification and Human Evolution'' ( 1962, Burg Wartenstein, Austria), where the term was formally introduced by Emil Zuckerkandl. In this time, Molecular Anthropology has developed both methodologically and theoretically and extended its applications, so covering key aspects of human evolution such as the reconstruction of the history of human populations and peopling processes, the characterization of DNA in extinct humans and the role of adaptive processes in shaping the genetic diversity of our species. In the current scientific panorama, molecular anthropologists have to face a double challenge. As members of the anthropological community, we are strongly committed to the integration of biological findings and other lines of evidence (e.g. linguistic and archaeological), while keeping in line with methodological innovations which are moving the approach from the genetic to the genomic level. In this framework, the meeting "DNA Polymorphisms in Human Populations: Molecular Anthropology in the Genomic Era" ( Rome, December 3-5, 2009) offered an opportunity for discussion among scholars from different disciplines, while paying attention to the impact of recent methodological innovations. Here we present an overview of the meeting and discuss perspectives and prospects of Molecular Anthropology in the genomic era

Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels

Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signals that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signals involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of release from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes