The protozoan Plasmodium vivax is responsible for 42% of all cases of malaria outside Africa. The parasite is currently largely restricted to tropical and subtropical latitudes in Asia, Oceania, and the Americas. Though, it was historically present in most of Europe before being finally eradicated during the second half of the 20th century. The lack of genomic information on the extinct European lineage has prevented a clear understanding of historical population structuring and past migrations of P. vivax. We used medical microscope slides prepared in 1944 from malaria-affected patients from the Ebro Delta in Spain, one of the last footholds of malaria in Europe, to generate a genome of a European P. vivax strain. Population genetics and phylogenetic analyses placed this strain basal to a cluster including samples from the Americas. This genome allowed us to calibrate a genomic mutation rate for P. vivax, and to estimate the mean age of the last common ancestor between European and American strains to the 15th century. This date points to an introduction of the parasite during the European colonization of the Americas. In addition, we found that some known variants for resistance to antimalarial drugs, including Chloroquine and Sulfadoxine, were already present in this European strain, predating their use. Our results shed light on the evolution of an important human pathogen and illustrate the value of antique medical collections as a resource for retrieving genomic information on pathogens from the past.

Malaria, caused by Plasmodium parasites, is thought to be one of the strongest selective forces that has shaped the genome of modern humans and was endemic in Europe until recent times. Due to its eradication around mid-twentieth century, the potential selective history of malaria in European populations is largely unknown. Here, we screen 224 ancient European genomes from the Upper Palaeolithic to the post-Roman period for 22 malaria-resistant alleles in twelve genes described in the literature. None of the most specific mutations for malaria resistance, like those at G6PD, HBB or Duffy blood group, have been detected among the available samples, while many other malaria-resistant alleles existed well before the advent of agriculture. We detected statistically significant differences between ancient and modern populations for the ATP2B4, FCGR2B and ABO genes and we found evidence of selection at IL-10 and ATP2B4 genes. However it is unclear whether malaria is the causative agent, because these genes are also involved in other immunological challenges. These results suggest that the selective force represented by malaria was relatively weak in Europe, a fact that could be associated to a recent historical introduction of the severe malaria pathogen.The malaria parasite Plasmodium falciparum is one of the main causes of child mortality worldwide, although other species from the same genus, P. vivax, P. malariae and P. ovale are also causative agents of the disease. Therefore, it is not surprising that malaria is one of the strongest known selective pressures that have recently shaped the human genome. Malaria is the evolutionary driving force behind sickle-cell disease (HbS), thalassemia, glucose-6-phosphatase deficiency (G6PD) and other erythrocyte defects that together comprise the most common Mendelian diseases of humankind. Remarkably, populations from different geographical areas have developed different genetic mechanisms adapted to malaria resistance; for instance, the HbS allele at the HBB gene is common in Africa but rare in Southeast Asia, whereas the HbE alelle shows a reversed pattern. Resistance to malaria includes primarily genes involved in immunological response, but also some involved in inflammation and cell adhesion and even genes related to metabolic pathways. The fact that different malaria-resistance alleles have arisen in different places suggests that this adaptation occurred relatively recent in human history, at least well after the Out of Africa migration 1 . P. falciparum may have rapidly spread from its African tropical origins to other tropical and subtropical regions of the world only within the last 6,000 years 2 . The recent origin of the worldwide P. falciparum populations, which are the most malignant of human malarial parasites, may account for its virulence 3 . Thus, haplotype analysis at the G6PD locus suggests that the African resistance allele to P. falciparum originated within the last 10,000 years 4 while a similar analysis at the HbE alleles (variants of the HBB gene) in...

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Malaria was present in most of Europe until the second half of the 20th century, when it was eradicated through a combination of increased surveillance and mosquito control strategies, together with cross-border and political collaboration. Despite the severe burden of malaria on human populations, it remains contentious how the disease arrived and spread in Europe. Here, we report a partial Plasmodium falciparum nuclear genome derived from a set of antique medical slides stained with the blood of malaria-infected patients from Spain’s Ebro Delta, dating to the 1940s. Our analyses of the genome of this now eradicated European P. falciparum strain confirms stronger phylogeographical affinity to present-day strains in circulation in central south Asia, rather than to those in Africa. This points to a longitudinal, rather than a latitudinal, spread of malaria into Europe. In addition, this genome displays two derived alleles in the pfmrp1 gene that have been associated with drug resistance. Whilst this could represent standing variation in the ancestral P. falciparum population, these mutations may also have arisen due to the selective pressure of quinine treatment, which was an anti-malarial drug already in use by the time the sample we sequenced was mounted on a slide.

Background Bioko is one of the few islands that exist around Africa, the most genetically diverse continent on the planet. The native Bantu-speaking inhabitants of Bioko, the Bubi, are believed to have colonized the island about 2000 years ago. Here, we sequenced the genome of thirteen Bubi individuals at high coverage and analysed their sequences in comparison to mainland populations from the Gulf of Guinea. Results We found that, genetically, the closest mainland population to the Bubi are Bantu-speaking groups from Angola instead the geographically closer groups from Cameroon. The Bubi possess a lower proportion of rainforest hunter-gatherer (RHG) ancestry than most other Bantu-speaking groups. However, their RHG component most likely came from the same source and could have reached them by gene flow from the mainland after island settlement. By studying identity by descent (IBD) genomic blocks and runs of homozygosity (ROHs), we found evidence for a significant level of genetic isolation among the Bubi, isolation that can be attributed to the island effect. Additionally, as this population is known to have one of the highest malaria incidence rates in the world we analysed their genome for malaria-resistant alleles. However, we were unable to detect any specific selective sweeps related to this disease. Conclusions By describing their dispersal to the Atlantic islands, the genomic characterization of the Bubi contributes to the understanding of the margins of the massive Bantu migration that shaped all Sub-Saharan African populations. Electronic supplementary material The online version of this article (10.1186/s12864-019-5529-0) contains supplementary material, which is available to authorized users.

The Xerces Blue (Glaucopsyche xerces) is considered to be the first butterfly to become extinct at global scale in historical times. It was notable for its chalky lavender wings with conspicuous white spots on the ventral wings. The last individuals were collected in their restricted habitat, in the dunes near the Presidio military base in San Francisco, in 1941. We sequenced the genomes of four 80 to 100-year-old Xerces Blue, and seven historical and one modern specimens of its closest relative, the Silvery Blue (G. lygdamus). We compared these to a novel annotated genome of the Green-Underside Blue (G. alexis). Phylogenetic relationships inferred from complete mitochondrial genomes indicate that Xerces Blue was a distinct species that diverged from the Silvery Blue lineage at least 850,000 years ago. Using nuclear genomes, both species experienced population growth during the Eemian interglacial period, but the Xerces Blue decreased to a very low effective population size subsequently, a trend opposite to that observed in the Silvery Blue. Runs of homozygosity and deleterious load in the Xerces Blue were significantly greater than in the Silvery Blue, suggesting a higher incidence of inbreeding. These signals of population decline observed in Xerces Blue could be used to identify and monitor other insects threatened by human activities, whose extinction patterns are still not well known.

Historical genetic links among similar populations can be difficult to establish. Identity by descent (IBD) analyses find genomic blocks that represent direct genealogical relationships among individuals. However, this method has rarely been applied to ancient genomes because IBD stretches are progressively fragmented by recombination and thus not recognizable after few tens of generations. To explore such genealogical relationships, we estimated long IBD blocks among modern Europeans, generating networks to uncover the genetic structures. We found that Basques, Sardinians, Icelanders and Orcadians form, each of them, highly intraconnected sub-clusters in a European network, indicating dense genealogical links within small, isolated populations. We also exposed individual genealogical links -such as the connection between one Basque and one Icelandic individual-that cannot be uncovered with other, widely used population genetics methods such as PCA or ADMIXTURE. Moreover, using ancient DNA technology we sequenced a Late Medieval individual (Barcelona, Spain) to high genomic coverage and identified IBD blocks shared between her and modern Europeans. The Medieval IBD blocks are statistically overrepresented only in modern Spaniards, which is the geographically closest population. This approach can be used to produce a fine-scale reflection of shared ancestry across different populations of the world, offering a direct genetic link from the past to the present.Many studies have demonstrated that human population genetic structuring in Europe correlates with geography; for instance, a two dimensional representation of the genetic variation with principal component analysis (PCA) essentially mirrors a geographical map of Europe 1,2 . Several ancient DNA (aDNA) studies have shown that the overall genetic structure was shaped by three ancestral and over-imposed genomic components respectively deriving from the Mesolithic hunter-gatherers, the Early Neolithic farmers, and the steppe nomads that entered Europe from the East around 5,000 years ago 3-7 . However, it is expected that the genetic homogenisation of the European populations during the last two millennia complicates our ability to discern subtle changes in ancestry by using some common population genetic tools.Complementary to these analyses, the distribution of so-called identity by descent (IBD) genomic stretches, which are co-inherited genetic segments delimited by recombination events, can provide information on more recently shared ancestry among individuals [8][9][10] . Such genomic block characterization in current populations has demonstrated the presence of co-ancestry across geographically distant Europeans shared over the last few thousand years, and revealed more recently shared co-ancestry in neighboring populations 11 . Nevertheless, most IBD blocks are not expected to be recognizable after a few hundreds of years because they are being broken by recombination during meiosis. Since the far majority of ancient human genomes sequenced to date are >2,...