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Qiaomei Fu,
Alissa Mittnik,
Philip L F Johnson,
Kirsten Bos,
Martina Lari,
Ruth Bollongino,
Chengkai Sun,
Liane Giemsch,
Ralf Schmitz,
Joachim Burger,
Anna Maria Ronchitelli,
Fabio Martini,
Renata G Cremonesi,
Jiří Svoboda,
Peter Bauer,
David Caramelli,
Sergi Castellano,
David Reich,
Svante Pääbo, Johannes Krause
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ABSTRACT: BACKGROUND: Recent analyses of de novo DNA mutations in modern humans have suggested a nuclear substitution rate that is approximately half that of previous estimates based on fossil calibration. This result has led to suggestions that major events in human evolution occurred far earlier than previously thought. RESULTS: Here, we use mitochondrial genome sequences from ten securely dated ancient modern humans spanning 40,000 years as calibration points for the mitochondrial clock, thus yielding a direct estimate of the mitochondrial substitution rate. Our clock yields mitochondrial divergence times that are in agreement with earlier estimates based on calibration points derived from either fossils or archaeological material. In particular, our results imply a separation of non-Africans from the most closely related sub-Saharan African mitochondrial DNAs (haplogroup L3) that occurred less than 62-95 kya. CONCLUSIONS: Though single loci like mitochondrial DNA (mtDNA) can only provide biased estimates of population divergence times, they can provide valid upper bounds. Our results exclude most of the older dates for African and non-African population divergences recently suggested by de novo mutation rate estimates in the nuclear genome.
Current biology: CB 03/2013; · 10.99 Impact Factor
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Katerina Guschanski, Johannes Krause,
Susanna Sawyer,
Luis M. Valente,
Sebastian Bailey,
Knut Finstermeier,
Richard Sabin,
Emmanuel Gilissen,
Gontran Sonet,
Zoltan T. Nagy,
Georges Lenglet,
Frieder Mayer,
Vincent Savolainen
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ABSTRACT: Guenons (tribe Cercopithecini) are one of the most diverse groups of primates. They occupy all of sub-Saharan Africa and show great variation in ecology, behavior, and morphology. This variation led to the description of over 60 species and subspecies. Here, using next-generation DNA sequencing (NGS) in combination with targeted DNA capture, we sequenced 92 mitochondrial genomes from museum-preserved specimens as old as 117 years. We infer evolutionary relationships and estimate divergence times of almost all guenon taxa based on mitochondrial genome sequences. Using this phylogenetic framework, we infer divergence dates and reconstruct ancestral geographic ranges. We conclude that the extraordinary radiation of guenons has been a complex process driven by, among other factors, localized fluctuations of African forest cover. We find incongruences between phylogenetic trees reconstructed from mitochondrial and nuclear DNA sequences, which can be explained by either incomplete lineage sorting or hybridization. Furthermore, having produced the largest mitochondrial DNA dataset from museum specimens, we document how NGS technologies can 'unlock' museum collections, thereby helping to unravel the tree-of-life.
Systematic Biology 03/2013; · 10.23 Impact Factor
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ABSTRACT: The successful reconstruction of an ancient bacterial genome from archaeological material presents an important methodological advancement for infectious disease research. The reliability of evolutionary histories inferred by the incorporation of ancient data, however, are highly contingent upon the level of genetic diversity represented in modern genomic sequences that are publicly accessible, and the paucity of available complete genomes restricts the level of phylogenetic resolution that can be obtained. Here we add to our original analysis of the Yersinia pestis strain implicated in the Black Death by consolidating our dataset for 18 modern genomes with single nucleotide polymorphism (SNP) data for an additional 289 strains at over 600 positions. The inclusion of this additional data reveals a cluster of Y. pestis strains that diverge at a time significantly in advance of the Black Death, with divergence dates roughly coincident with the Plague of Justinian (6(th) to 8(th) century AD). In addition, the analysis reveals further clues regarding potential radiation events that occurred immediately preceding the Black Death, and the legacy it may have left in modern Y. pestis populations. This work reiterates the need for more publicly available complete genomes, both modern and ancient, to achieve an accurate understanding of the history of this bacterium.
PLoS ONE 01/2012; 7(11):e49803. · 4.09 Impact Factor
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ABSTRACT: DNA that survives in museum specimens, bones and other tissues recovered by archaeologists is invariably fragmented and chemically modified. The extent to which such modifications accumulate over time is largely unknown but could potentially be used to differentiate between endogenous old DNA and present-day DNA contaminating specimens and experiments. Here we examine mitochondrial DNA sequences from tissue remains that vary in age between 18 and 60,000 years with respect to three molecular features: fragment length, base composition at strand breaks, and apparent C to T substitutions. We find that fragment length does not decrease consistently over time and that strand breaks occur preferentially before purine residues by what may be at least two different molecular mechanisms that are not yet understood. In contrast, the frequency of apparent C to T substitutions towards the 5'-ends of molecules tends to increase over time. These nucleotide misincorporations are thus a useful tool to distinguish recent from ancient DNA sources in specimens that have not been subjected to unusual or harsh treatments.
PLoS ONE 01/2012; 7(3):e34131. · 4.09 Impact Factor
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ABSTRACT: The Neolithic transition from hunting and gathering to farming and cattle breeding marks one of the most drastic cultural changes in European prehistory. Short stretches of ancient mitochondrial DNA (mtDNA) from skeletons of pre-Neolithic hunter-gatherers as well as early Neolithic farmers support the demic diffusion model where a migration of early farmers from the Near East and a replacement of pre-Neolithic hunter-gatherers are largely responsible for cultural innovation and changes in subsistence strategies during the Neolithic revolution in Europe. In order to test if a signal of population expansion is still present in modern European mitochondrial DNA, we analyzed a comprehensive dataset of 1,151 complete mtDNAs from present-day Europeans. Relying upon ancient DNA data from previous investigations, we identified mtDNA haplogroups that are typical for early farmers and hunter-gatherers, namely H and U respectively. Bayesian skyline coalescence estimates were then used on subsets of complete mtDNAs from modern populations to look for signals of past population expansions. Our analyses revealed a population expansion between 15,000 and 10,000 years before present (YBP) in mtDNAs typical for hunters and gatherers, with a decline between 10,000 and 5,000 YBP. These corresponded to an analogous population increase approximately 9,000 YBP for mtDNAs typical of early farmers. The observed changes over time suggest that the spread of agriculture in Europe involved the expansion of farming populations into Europe followed by the eventual assimilation of resident hunter-gatherers. Our data show that contemporary mtDNA datasets can be used to study ancient population history if only limited ancient genetic data is available.
PLoS ONE 01/2012; 7(3):e32473. · 4.09 Impact Factor
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Kirsten I Bos,
Verena J Schuenemann,
G Brian Golding,
Hernán A Burbano,
Nicholas Waglechner,
Brian K Coombes,
Joseph B McPhee,
Sharon N Dewitte,
Matthias Meyer,
Sarah Schmedes,
James Wood,
David J D Earn,
D Ann Herring,
Peter Bauer,
Hendrik N. Poinar, Johannes Krause
Nature 12/2011; 480(7376):278. · 36.28 Impact Factor
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Kirsten I Bos,
Verena J Schuenemann,
G Brian Golding,
Hernán A Burbano,
Nicholas Waglechner,
Brian K Coombes,
Joseph B McPhee,
Sharon N DeWitte,
Matthias Meyer,
Sarah Schmedes,
James Wood,
David J D Earn,
D Ann Herring,
Peter Bauer,
Hendrik N Poinar, Johannes Krause
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ABSTRACT: Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.
Nature 10/2011; 478(7370):506-10. · 36.28 Impact Factor
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Verena J Schuenemann,
Kirsten Bos,
Sharon DeWitte,
Sarah Schmedes,
Joslyn Jamieson,
Alissa Mittnik,
Stephen Forrest,
Brian K Coombes,
James W Wood,
David J D Earn,
William White, Johannes Krause,
Hendrik N Poinar
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ABSTRACT: Although investigations of medieval plague victims have identified Yersinia pestis as the putative etiologic agent of the pandemic, methodological limitations have prevented large-scale genomic investigations to evaluate changes in the pathogen's virulence over time. We screened over 100 skeletal remains from Black Death victims of the East Smithfield mass burial site (1348-1350, London, England). Recent methods of DNA enrichment coupled with high-throughput DNA sequencing subsequently permitted reconstruction of ten full human mitochondrial genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at high coverage. Comparisons of molecular damage profiles between endogenous human and Y. pestis DNA confirmed its authenticity as an ancient pathogen, thus representing the longest contiguous genomic sequence for an ancient pathogen to date. Comparison of our reconstructed plasmid against modern Y. pestis shows identity with several isolates matching the Medievalis biovar; however, our chromosomal sequences indicate the victims were infected with a Y. pestis variant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that may no longer exist, and genetic data carried on its pPCP1 plasmid were not responsible for the purported epidemiological differences between ancient and modern forms of Y. pestis infections.
Proceedings of the National Academy of Sciences 08/2011; 108(38):E746-52. · 9.68 Impact Factor
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David Reich,
Richard E Green,
Martin Kircher, Johannes Krause,
Nick Patterson,
Eric Y Durand,
Bence Viola,
Adrian W Briggs,
Udo Stenzel,
Philip L F Johnson, [......],
Evan E Eichler,
Mark Stoneking,
Michael Richards,
Sahra Talamo,
Michael V Shunkov,
Anatoli P Derevianko,
Jean-Jacques Hublin,
Janet Kelso,
Montgomery Slatkin,
Svante Pääbo
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ABSTRACT: Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4-6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population 'Denisovans' and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans.
Nature 12/2010; 468(7327):1053-60. · 36.28 Impact Factor
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Hernán A Burbano,
Emily Hodges,
Richard E Green,
Adrian W Briggs, Johannes Krause,
Matthias Meyer,
Jeffrey M Good,
Tomislav Maricic,
Philip L F Johnson,
Zhenyu Xuan,
Michelle Rooks,
Arindam Bhattacharjee,
Leonardo Brizuela,
Frank W Albert,
Marco de la Rasilla,
Javier Fortea,
Antonio Rosas,
Michael Lachmann,
Gregory J Hannon,
Svante Pääbo
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ABSTRACT: It is now possible to perform whole-genome shotgun sequencing as well as capture of specific genomic regions for extinct organisms. However, targeted resequencing of large parts of nuclear genomes has yet to be demonstrated for ancient DNA. Here we show that hybridization capture on microarrays can successfully recover more than a megabase of target regions from Neandertal DNA even in the presence of approximately 99.8% microbial DNA. Using this approach, we have sequenced approximately 14,000 protein-coding positions inferred to have changed on the human lineage since the last common ancestor shared with chimpanzees. By generating the sequence of one Neandertal and 50 present-day humans at these positions, we have identified 88 amino acid substitutions that have become fixed in humans since our divergence from the Neandertals.
Science 05/2010; 328(5979):723-5. · 31.20 Impact Factor
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Richard E Green, Johannes Krause,
Adrian W Briggs,
Tomislav Maricic,
Udo Stenzel,
Martin Kircher,
Nick Patterson,
Heng Li,
Weiwei Zhai,
Markus Hsi-Yang Fritz, [......],
Evan E Eichler,
Daniel Falush,
Ewan Birney,
James C Mullikin,
Montgomery Slatkin,
Rasmus Nielsen,
Janet Kelso,
Michael Lachmann,
David Reich,
Svante Pääbo
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ABSTRACT: Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.
Science 05/2010; 328(5979):710-22. · 31.20 Impact Factor
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ABSTRACT: With the exception of Neanderthals, from which DNA sequences of numerous individuals have now been determined, the number and genetic relationships of other hominin lineages are largely unknown. Here we report a complete mitochondrial (mt) DNA sequence retrieved from a bone excavated in 2008 in Denisova Cave in the Altai Mountains in southern Siberia. It represents a hitherto unknown type of hominin mtDNA that shares a common ancestor with anatomically modern human and Neanderthal mtDNAs about 1.0 million years ago. This indicates that it derives from a hominin migration out of Africa distinct from that of the ancestors of Neanderthals and of modern humans. The stratigraphy of the cave where the bone was found suggests that the Denisova hominin lived close in time and space with Neanderthals as well as with modern humans.
Nature 03/2010; 464(7290):894-7. · 36.28 Impact Factor
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ABSTRACT: The recovery of DNA sequences from early modern humans (EMHs) could shed light on their interactions with archaic groups such as Neandertals and their relationships to current human populations. However, such experiments are highly problematic because present-day human DNA frequently contaminates bones [1, 2]. For example, in a recent study of mitochondrial (mt) DNA from Neolithic European skeletons, sequence variants were only taken as authentic if they were absent or rare in the present population, whereas others had to be discounted as possible contamination [3, 4]. This limits analysis to EMH individuals carrying rare sequences and thus yields a biased view of the ancient gene pool. Other approaches of identifying contaminating DNA, such as genotyping all individuals who have come into contact with a sample, restrict analyses to specimens where this is possible [5, 6] and do not exclude all possible sources of contamination. By studying mtDNA in Neandertal remains, where contamination and endogenous DNA can be distinguished by sequence, we show that fragmentation patterns and nucleotide misincorporations can be used to gauge authenticity of ancient DNA sequences. We use these features to determine a complete mtDNA sequence from a approximately 30,000-year-old EMH from the Kostenki 14 site in Russia.
Current biology: CB 02/2010; 20(3):231-6. · 10.99 Impact Factor
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ABSTRACT: DNA sequences determined from ancient organisms have high error rates, primarily due to uracil bases created by cytosine deamination. We use synthetic oligonucleotides, as well as DNA extracted from mammoth and Neandertal remains, to show that treatment with uracil-DNA-glycosylase and endonuclease VIII removes uracil residues from ancient DNA and repairs most of the resulting abasic sites, leaving undamaged parts of the DNA fragments intact. Neandertal DNA sequences determined with this protocol have greatly increased accuracy. In addition, our results demonstrate that Neandertal DNA retains in vivo patterns of CpG methylation, potentially allowing future studies of gene inactivation and imprinting in ancient organisms.
Nucleic Acids Research 12/2009; 38(6):e87. · 8.03 Impact Factor
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ABSTRACT: Recent advances in high-thoughput DNA sequencing have made genome-scale analyses of genomes of extinct organisms possible. With these new opportunities come new difficulties in assessing the authenticity of the DNA sequences retrieved. We discuss how these difficulties can be addressed, particularly with regard to analyses of the Neandertal genome. We argue that only direct assays of DNA sequence positions in which Neandertals differ from all contemporary humans can serve as a reliable means to estimate human contamination. Indirect measures, such as the extent of DNA fragmentation, nucleotide misincorporations, or comparison of derived allele frequencies in different fragment size classes, are unreliable. Fortunately, interim approaches based on mtDNA differences between Neandertals and current humans, detection of male contamination through Y chromosomal sequences, and repeated sequencing from the same fossil to detect autosomal contamination allow initial large-scale sequencing of Neandertal genomes. This will result in the discovery of fixed differences in the nuclear genome between Neandertals and current humans that can serve as future direct assays for contamination. For analyses of other fossil hominins, which may become possible in the future, we suggest a similar 'boot-strap' approach in which interim approaches are applied until sufficient data for more definitive direct assays are acquired.
The EMBO Journal 09/2009; 28(17):2494-502. · 9.20 Impact Factor
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ABSTRACT: Recent advances in high-thoughput DNA sequencing have made genome-scale analyses of genomes of extinct organisms possible. With these new opportunities come new difficulties in assessing the authenticity of the DNA sequences retrieved. We discuss how these difficulties can be addressed, particularly with regard to analyses of the Neandertal genome. We argue that only direct assays of DNA sequence positions in which Neandertals differ from all contemporary humans can serve as a reliable means to estimate human contamination. Indirect measures, such as the extent of DNA fragmentation, nucleotide misincorporations, or comparison of derived allele frequencies in different fragment size classes, are unreliable. Fortunately, interim approaches based on mtDNA differences between Neandertals and current humans, detection of male contamination through Y chromosomal sequences, and repeated sequencing from the same fossil to detect autosomal contamination allow initial large-scale sequencing of Neandertal genomes. This will result in the discovery of fixed differences in the nuclear genome between Neandertals and current humans that can serve as future direct assays for contamination. For analyses of other fossil hominins, which may become possible in the future, we suggest a similar ‘boot-strap’ approach in which interim approaches are applied until sufficient data for more definitive direct assays are acquired.
The EMBO Journal 08/2009; 28(17):2494-2502. · 9.20 Impact Factor
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ABSTRACT: Polymorphism data in humans suggest that the gene encoding the transcription factor FOXP2, which influences speech and language development, has been subject to a selective sweep within the last 260,000 years. It has been proposed that one or both of two substitutions that occurred on the human evolutionary lineage and changed amino acids were the targets for selection. In apparent contradiction to this is the observation that these substitutions are present in Neandertals who diverged from humans maybe 300,000-400,000 years ago. We have collected polymorphism data upstream and downstream of the substitutions. Contrary to what is expected, following a selective sweep, we find that the haplotypes extend across the two sites. We discuss possible explanations for these observations. One of them is that the selective sweep reflected in FOXP2 polymorphism data was not associated with the two amino acid substitutions.
Molecular Biology and Evolution 08/2009; 26(10):2181-4. · 5.55 Impact Factor
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Adrian W Briggs,
Jeffrey M Good,
Richard E Green, Johannes Krause,
Tomislav Maricic,
Udo Stenzel,
Carles Lalueza-Fox,
Pavao Rudan,
Dejana Brajkovic,
Zeljko Kucan,
Ivan Gusic,
Ralf Schmitz,
Vladimir B Doronichev,
Liubov V Golovanova,
Marco de la Rasilla,
Javier Fortea,
Antonio Rosas,
Svante Pääbo
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ABSTRACT: Analysis of Neandertal DNA holds great potential for investigating the population history of this group of hominins, but progress has been limited due to the rarity of samples and damaged state of the DNA. We present a method of targeted ancient DNA sequence retrieval that greatly reduces sample destruction and sequencing demands and use this method to reconstruct the complete mitochondrial DNA (mtDNA) genomes of five Neandertals from across their geographic range. We find that mtDNA genetic diversity in Neandertals that lived 38,000 to 70,000 years ago was approximately one-third of that in contemporary modern humans. Together with analyses of mtDNA protein evolution, these data suggest that the long-term effective population size of Neandertals was smaller than that of modern humans and extant great apes.
Science 08/2009; 325(5938):318-21. · 31.20 Impact Factor
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ABSTRACT: We present a method of targeted DNA sequence retrieval from DNA sources which are heavily degraded and contaminated with microbial DNA, as is typical of ancient bones. The method greatly reduces sample destruction and sequencing demands relative to direct PCR or shotgun sequencing approaches. We used this method to reconstruct the complete mitochondrial DNA (mtDNA) genomes of five Neandertals from across their geographic range. The mtDNA genetic diversity of the late Neandertals was approximately three times lower than that of contemporary modern humans. Together with analyses of mtDNA protein evolution, these data suggest that the long-term effective population size of Neandertals was smaller than that of modern humans and extant great apes.
Journal of Visualized Experiments 02/2009;
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ABSTRACT: The high polymorphism rate in the human ABO blood group gene seems to be related to susceptibility to different pathogens. It has been estimated that all genetic variation underlying the human ABO alleles appeared along the human lineage, after the divergence from the chimpanzee lineage. A paleogenetic analysis of the ABO blood group gene in Neandertals allows us to directly test for the presence of the ABO alleles in these extinct humans.
We have analysed two male Neandertals that were retrieved under controlled conditions at the El Sidron site in Asturias (Spain) and that appeared to be almost free of modern human DNA contamination. We find a human specific diagnostic deletion for blood group O (O01 haplotype) in both Neandertal individuals.
These results suggest that the genetic change responsible for the O blood group in humans predates the human and Neandertal divergence. A potential selective event associated with the emergence of the O allele may have therefore occurred after humans separated from their common ancestor with chimpanzees and before the human-Neandertal population divergence.
BMC Evolutionary Biology 01/2009; 8:342. · 3.52 Impact Factor
