Adressing Neandertal evolutionary genetics at three different resolution levels : admixture with modern humans, demography and social structure

Almost 20 years of Neandertal paleogenetics studies have significantly increased our knowledge about their evolutionary history. The analysis of DNA recovered from Neandertal remains to date, suggest that although they were a distinct hominin population to modern humans, a certain degree of gene flow occurred between the two of them. Furthermore, recent evidence suggests that archaic introgressed material could have been biologically relevant for modern humans to adapt to new environments. Moreover, insights from a wide geographic and temporally different sampling of Neandertal mitochondrial sequences and from a high-coverage genome, suggest that Neandertals probably had a low effective population, which was possibly decreasing towards the end of their evolutionary time. This thesis focus to address the evolutionary genetic history of Neandertals at three different levels of resolution from: analyzing further aspects of their relatedness to modern humans, better characterizing their population history and identify the genetic basis for some of their distinctive morphological features, to describing their genetic structure within a social group. Insights from these three lines of research intend to reconstruct key aspects of their population history and its implications towards their eventual demise.Casi veinte años de estudios de paleogenética Neandertal han incrementado significativamente nuestro conocimiento sobre su historia evolutiva. El análisis de secuencias genéticas recuperadas a partir de fósiles Neandertales, sugiere que a pesar de que éstos era un grupo de homínidos diferentes a los humanos modernos, cierta grado de introgresión genética ocurrió de Neandertales hacia humanos modernos. Más aún, estudios recientes sugieren que el material genético introducido a éstos pudo haber sido relevante biológicamente para adaptarse a nuevos ambientes. Por otro lado, inferencias a partir de datos genéticos mitocondriales provenientes de muestras de diferentes zonas geográficas y origen temporal, a la par con la secuencia de un genoma completo de alta calidad sugieren que los Neandertales tenían un tamaño efectivo de población reducido y que probablemente estaba disminuyendo hacia el final de su tiempo. La tesis aquí presentada, se enfoca a abordar la historia evolutiva Neandertal a tres niveles de resolución diferentes, analizando datos genéticos provenientes de fósiles. Primero, se analizan otros posibles eventos de introgresión genética con humanos modernos, no descritos hasta la fecha. Posteriormente, se caracteriza a detalle su demografía e identifica cambios específicos para su linaje evolutivo que podrían estar relacionados con las bases genéticas de algunos de sus rasgos morfológicos más distintivos. Finalmente, se describe la estructura genética y dinámica de un grupo social Neandertal. Las perspectivas de estas tres líneas de investigación pretenden no sólo reconstruir aspectos claves de su historia evolutiva, sino también entender las consecuencias que ésta pudo haber tenido con su eventual extinción

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.CL-F, OR and SC are supported by a grant from the Ministerio de Innovación y Ciencia from Spain (BFU2009-06974). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

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 Neandertal's 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.FS-Q, SC, CA and CL-F are supported by a grant from the Ministerio de Ciencia e Innovación of Spain (BFU2009-06974) and CGL2010-14944/BOS

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.The POPRES data were obtained from dbGaP (accession number # 2038). The Danish National Research Foundation, ERC Starting Grant (260372) to TM-B, and (310372) to MGN, FEDER and Spanish Government Grants BFU2009-13409-C02-02, BFU2012-38236 to AN, BFU2011-28549 to TM-B, BFU2012-34157 to CL-F, ERC (Marie Cure Actions) to MEA, NIH NRSA postdoctoral fellowship (F32GM106656) to CWKC, NIH (R01-HG007089) to JN, NSF postdoctoral fellowship (DBI-1103639) to MD

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 gourd's genome does not seem compatible with Louis XVI's 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.This work is supported by FEDER and Spanish Government grants BFU2012-38236 and the Spanish Multiple Sclerosis Netowrk (REEM) of the Instituto de Salud Carlos III (RD12/0032/0011) to A.N., BFU2011-28549 and ERC Starting Grant (260372) to T.M.-B. and BFU2012-34157 to C.L.-F. and S.C., and a predoctoral fellowship from the Basque Government (DEUI) to I.

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 gourd's genome does not seem compatible with Louis XVI's 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.This work is supported by FEDER and Spanish Government grants BFU2012-38236 and the Spanish Multiple Sclerosis Netowrk (REEM) of the Instituto de Salud Carlos III (RD12/0032/0011) to A.N., BFU2011-28549 and ERC Starting Grant (260372) to T.M.-B. and BFU2012-34157 to C.L.-F. and S.C., and a predoctoral fellowship from the Basque Government (DEUI) to I.