Federico Sánchez-Quinto

Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European

Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Braña-Arintero site in León, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer.

Patterns of coding variation in the complete exomes of three Neandertals

Significance We use a hybridization approach to enrich the DNA from the protein-coding fraction of the genomes of two Neandertal individuals from Spain and Croatia. By analyzing these two exomes together with the genome sequence of a Neandertal from Siberia we show that the genetic diversity of Neandertals was lower than that of present-day humans and that the pattern of coding variation suggests that Neandertal populations were small and isolated from one another. We also show that genes involved in skeletal morphology have changed more than expected on the Neandertal evolutionary lineage whereas genes involved in pigmentation and behavior have changed more on the modern human lineage. We present the DNA sequence of 17,367 protein-coding genes in two Neandertals from Spain and Croatia and analyze them together with the genome sequence recently determined from a Neandertal from southern Siberia. Comparisons with present-day humans from Africa, Europe, and Asia reveal that genetic diversity among Neandertals was remarkably low, and that they carried a higher proportion of amino acid-changing (nonsynonymous) alleles inferred to alter protein structure or function than present-day humans. Thus, Neandertals across Eurasia had a smaller long-term effective population than present-day humans. We also identify amino acid substitutions in Neandertals and present-day humans that may underlie phenotypic differences between the two groups. We find that genes involved in skeletal morphology have changed more in the lineage leading to Neandertals than in the ancestral lineage common to archaic and modern humans, whereas genes involved in behavior and pigmentation have changed more on the modern human lineage.

Genetic evidence for patrilocal mating behavior among Neandertal groups

The remains of 12 Neandertal individuals have been found at the El Sidrón site (Asturias, Spain), consisting of six adults, three adolescents, two juveniles, and one infant. Archaeological, paleontological, and geological evidence indicates that these individuals represent all or part of a contemporaneous social group of Neandertals, who died at around the same time and later were buried together as a result of a collapse of an underground karst. We sequenced phylogenetically informative positions of mtDNA hypervariable regions 1 and 2 from each of the remains. Our results show that the 12 individuals stem from three different maternal lineages, accounting for seven, four, and one individual(s), respectively. Using a Y-chromosome assay to confirm the morphological determination of sex for each individual, we found that, although the three adult males carried the same mtDNA lineage, each of the three adult females carried different mtDNA lineages. These findings provide evidence to indicate that Neandertal groups not only were small and characterized by low genetic diversity but also were likely to have practiced patrilocal mating behavior.

Genomic Affinities of Two 7,000-Year-Old Iberian Hunter-Gatherers

The genetic background of the European Mesolithic and the extent of population replacement during the Neolithic is poorly understood, both due to the scarcity of human remains from that period and the inherent methodological difficulties of ancient DNA research. However, advances in sequencing technologies are both increasing data yields and providing supporting evidence for data authenticity, such as nucleotide misincorporation patterns. We use these methods to characterize both the mitochondrial DNA genome and generate shotgun genomic data from two exceptionally well-preserved 7,000-year-old Mesolithic individuals from La Braña-Arintero site in León (Northwestern Spain). The mitochondria of both individuals are assigned to U5b2c1, a haplotype common among the small number of other previously studied Mesolithic individuals from Northern and Central Europe. This suggests a remarkable genetic uniformity and little phylogeographic structure over a large geographic area of the pre-Neolithic populations. Using Approximate Bayesian Computation, a model of genetic continuity from Mesolithic to Neolithic populations is poorly supported. Furthermore, analyses of 1.34% and 0.53% of their nuclear genomes, containing about 50,000 and 20,000 ancestry informative SNPs, respectively, show that these two Mesolithic individuals are not related to current populations from either the Iberian Peninsula or Southern Europe.

Population Genomic Analysis of Ancient and Modern Genomes Yields New Insights into the Genetic Ancestry of the Tyrolean Iceman and the Genetic Structure of Europe

Genome sequencing of the 5,300-year-old mummy of the Tyrolean Iceman, found in 1991 on a glacier near the border of Italy and Austria, has yielded new insights into his origin and relationship to modern European populations. A key finding of that study was an apparent recent common ancestry with individuals from Sardinia, based largely on the Y chromosome haplogroup and common autosomal SNP variation. Here, we compiled and analyzed genomic datasets from both modern and ancient Europeans, including genome sequence data from over 400 Sardinians and two ancient Thracians from Bulgaria, to investigate this result in greater detail and determine its implications for the genetic structure of Neolithic Europe. Using whole-genome sequencing data, we confirm that the Iceman is, indeed, most closely related to Sardinians. Furthermore, we show that this relationship extends to other individuals from cultural contexts associated with the spread of agriculture during the Neolithic transition, in contrast to individuals from a hunter-gatherer context. We hypothesize that this genetic affinity of ancient samples from different parts of Europe with Sardinians represents a common genetic component that was geographically widespread across Europe during the Neolithic, likely related to migrations and population expansions associated with the spread of agriculture.

North African Populations Carry the Signature of Admixture with Neandertals

One of the main findings derived from the analysis of the Neandertal genome was the evidence for admixture between Neandertals and non-African modern humans. An alternative scenario is that the ancestral population of non-Africans was closer to Neandertals than to Africans because of ancient population substructure. Thus, the study of North African populations is crucial for testing both hypotheses. We analyzed a total of 780,000 SNPs in 125 individuals representing seven different North African locations and searched for their ancestral/derived state in comparison to different human populations and Neandertals. We found that North African populations have a significant excess of derived alleles shared with Neandertals, when compared to sub-Saharan Africans. This excess is similar to that found in non-African humans, a fact that can be interpreted as a sign of Neandertal admixture. Furthermore, the Neandertals genetic signal is higher in populations with a local, pre-Neolithic North African ancestry. Therefore, the detected ancient admixture is not due to recent Near Eastern or European migrations. Sub-Saharan populations are the only ones not affected by the admixture event with Neandertals.

Fragmentation of Contaminant and Endogenous DNA in Ancient Samples Determined by Shotgun Sequencing; Prospects for Human Palaeogenomics

Background Despite the successful retrieval of genomes from past remains, the prospects for human palaeogenomics remain unclear because of the difficulty of distinguishing contaminant from endogenous DNA sequences. Previous sequence data generated on high-throughput sequencing platforms indicate that fragmentation of ancient DNA sequences is a characteristic trait primarily arising due to depurination processes that create abasic sites leading to DNA breaks. Methodology/Principals Findings To investigate whether this pattern is present in ancient remains from a temperate environment, we have 454-FLX pyrosequenced different samples dated between 5,500 and 49,000 years ago: a bone from an extinct goat (Myotragus balearicus) that was treated with a depurinating agent (bleach), an Iberian lynx bone not subjected to any treatment, a human Neolithic sample from Barcelona (Spain), and a Neandertal sample from the El Sidrón site (Asturias, Spain). The efficiency of retrieval of endogenous sequences is below 1% in all cases. We have used the non-human samples to identify human sequences (0.35 and 1.4%, respectively), that we positively know are contaminants. Conclusions We observed that bleach treatment appears to create a depurination-associated fragmentation pattern in resulting contaminant sequences that is indistinguishable from previously described endogenous sequences. Furthermore, the nucleotide composition pattern observed in 5′ and 3′ ends of contaminant sequences is much more complex than the flat pattern previously described in some Neandertal contaminants. Although much research on samples with known contaminant histories is needed, our results suggest that endogenous and contaminant sequences cannot be distinguished by the fragmentation pattern alone.

Almost 20 years of Neanderthal palaeogenetics: adaptation, admixture, diversity, demography and extinction

Nearly two decades since the first retrieval of Neanderthal DNA, recent advances in next-generation sequencing technologies have allowed the generation of high-coverage genomes from two archaic hominins, a Neanderthal and a Denisovan, as well as a complete mitochondrial genome from remains which probably represent early members of the Neanderthal lineage. This genomic information, coupled with diversity exome data from several Neanderthal specimens is shedding new light on evolutionary processes such as the genetic basis of Neanderthal and modern human-specific adaptations—including morphological and behavioural traits—as well as the extent and nature of the admixture events between them. An emerging picture is that Neanderthals had a long-term small population size, lived in small and isolated groups and probably practised inbreeding at times. Deleterious genetic effects associated with these demographic factors could have played a role in their extinction. The analysis of DNA from further remains making use of new large-scale hybridization-capture-based methods as well as of new approaches to discriminate contaminant DNA sequences will provide genetic information in spatial and temporal scales that could help clarify the Neanderthals—and our very own—evolutionary history.

A new subclade of mtDNA haplogroup C1 found in icelanders: Evidence of pre-columbian contact?

Although most mtDNA lineages observed in contemporary Icelanders can be traced to neighboring populations in the British Isles and Scandinavia, one may have a more distant origin. This lineage belongs to haplogroup C1, one of a handful that was involved in the settlement of the Americas around 14,000 years ago. Contrary to an initial assumption that this lineage was a recent arrival, preliminary genealogical analyses revealed that the C1 lineage was present in the Icelandic mtDNA pool at least 300 years ago. This raised the intriguing possibility that the Icelandic C1 lineage could be traced to Viking voyages to the Americas that commenced in the 10th century. In an attempt to shed further light on the entry date of the C1 lineage into the Icelandic mtDNA pool and its geographical origin, we used the deCODE Genetics genealogical database to identify additional matrilineal ancestors that carry the C1 lineage and then sequenced the complete mtDNA genome of 11 contemporary C1 carriers from four different matrilines. Our results indicate a latest possible arrival date in Iceland of just prior to 1700 and a likely arrival date centuries earlier. Most surprisingly, we demonstrate that the Icelandic C1 lineage does not belong to any of the four known Native American (C1b, C1c, and C1d) or Asian (C1a) subclades of haplogroup C1. Rather, it is presently the only known member of a new subclade, C1e. While a Native American origin seems most likely for C1e, an Asian or European origin cannot be ruled out.

Genomic analysis of the blood attributed to Louis XVI (1754–1793), king of France

A pyrographically decorated gourd, dated to the French Revolution period, has been alleged to contain a handkerchief dipped into the blood of the French king Louis XVI (1754–1793) after his beheading but recent analyses of living males from two Bourbon branches cast doubts on its authenticity. We sequenced the complete genome of the DNA contained in the gourd at low coverage (~2.5×) with coding sequences enriched at a higher ~7.3× coverage. We found that the ancestry of the gourds genome does not seem compatible with Louis XVIs known ancestry. From a functional perspective, we did not find an excess of alleles contributing to height despite being described as the tallest person in Court. In addition, the eye colour prediction supported brown eyes, while Louis XVI had blue eyes. This is the first draft genome generated from a person who lived in a recent historical period; however, our results suggest that this sample may not correspond to the alleged king.