Draft version of the Neanderthal genome completed

February 12, 2009

The Max Planck Institute for Evolutionary Anthropology, in Leipzig, Germany, and the 454 Life Sciences Corporation, in Branford, Connecticut, will announce on 12 February during the 2009 Annual Meeting of the American Association for the Advancement of Science (AAAS) and at a simultaneous European press briefing that they have completed a first draft version of the Neandertal genome.

The project, made possible by financing from the Max Planck Society, is directed by Prof. Svante Pääbo, Director of the Institute's Department of Evolutionary GeneticsAnthropology. Pääbo and his colleagues have sequenced more than one billion DNA fragments extracted from three Croatian Neandertal fossils, using novel methods developed for this project. The Neandertal genome sequence will clarify the evolutionary relationship between humans and Neandertals as well as help identify those genetic changes that enabled modern humans to leave Africa and rapidly spread around the world, starting around 100,000 years ago.

Neandertals were the closest relatives of currently living humans. They lived in Europe and parts of Asia until they became extinct about 30,000 years ago. For more than a hundred years, paleontologists and anthropologists have been striving to uncover their evolutionary relationship to modern humans. Pääbo, a pioneer in the field of ancient DNA research, made the first contribution to the understanding of our genetic relationship to Neandertals when he sequenced Neandertal mitochondrial DNA in 1997. Together with the company 454 Life Sciences, Pääbo has now announced a new milestone in Neandertal research. The two groups have sequenced a total of more than 3 billion bases of Neandertal DNA, generating a first draft sequence of the entire Neandertal genome. Altogether, these fragments make up more than 60% of the entire Neandertal genome. These DNA sequences can now be compared to the previously sequenced human and chimpanzee genomes in order to arrive at some initial insights into how the genome of this extinct form differed from that of modern humans.

In 2006, Pääbo's group published papers together with 454 Life Sciences that showed that it was possible to use the 454 technology to determine large amounts of nuclear DNA sequences from late Pleistocene animals such as mammoths as well as the Neandertal. Building on these results, Pääbo and Dr. Michael Egholm, Vice President of Research and Technology of 454 Life Sciences, a Roche Company, initiated an ambitious project to sequence the Neandertal genome. Together, the groups have overcome a number of technical obstacles in order to arrive at this first view of the entire genome of an extinct form of human.

One essential element developed by Pääbo's group was the production of sequencing libraries under "clean-room" conditions to avoid contamination of experiments by human DNA. They also designed DNA sequence tags that carry unique identifiers and are attached to the ancient DNA molecules in the clean room. This makes it possible to avoid contamination from other sources of DNA during the sequencing procedure, which was a problem in the initial proof-of-principle experiments in 2006. They also used minute amounts of radioactively labeled DNA to identify and modify those steps in the sequencing procedure where losses occur. Together with other advances implemented during the project, these innovations drastically reduced the need for precious fossil material so that less than half a gram of bone was used to produce the draft sequence of 3 billion base pairs.

In order to reliably compare the Neandertal DNA sequences to those of humans and chimpanzees, the Leipzig group has performed detailed studies of where chemical damage tends to occur in the ancient DNA and how it causes errors in the DNA sequences. The researchers found that such errors occur most frequently towards the ends of molecules and that the vast majority of them are due to a particular modification of one of the bases in the DNA that occurs over time in fossil remains. They then applied this knowledge to identify which of the DNA fragments from the fossils come from the Neandertal genome and which from microorganisms that have colonized the bones during the thousands of years they lay buried in the caves. They have also developed novel and more sensitive computer algorithms to put the Neandertal DNA fragments in order and compare them to the human genome.

In total, the group has determined over 100 million DNA sequence fragments from fossils by the 454 technology and over a billion DNA sequences with the Solexa technology, another sequencing technology which is particularly efficient in reading many short sequences. The majority of the sequence comes from Neandertal bones from Vindija Cave in Croatia, which the group studies as a part of a long-term collaboration between the Croatian Academy of Sciences and Arts and the Berlin-Brandenburg Academy. In order to test if the findings from this Neandertal are typical of those of other Neandertals, the researchers have also sequenced several million base pairs from Neandertals from other sites. Professor Javier Fortea and colleagues from Oviedo, Spain, have excavated 43,000-year-old Neandertal bones under sterile conditions at El Sidron, Spain, that have yielded DNA sequences, while Dr. Lubov Golovanova and Dr. Vladimir Doronichev from St. Petersburg, Russia, have contributed a 60-70,000-year-old bone from Mezmaiskaya Cave in the Caucasus. In addition, Dr. Ralf Schmitz from the LVR-Landesmuseum in Bonn, Germany has allowed a sample to be removed from the 40,000-year-old Neandertal type specimen, which was found in 1856 in the Neander Valley, the source of the name, Neandertal. This will allow crucial findings from the Croatian Neandertal to be verified in several Neandertals including the specimen that defines the Neandertals as a distinct group.

In order to aid in the analysis of the Neandertal genome, Dr. Pääbo has organized a consortium of researchers from around the world that plans to publish their results later this year. They will look at many genes of special interest in recent human evolution, such as FOXP2, which is involved in speech and language in modern humans, as well as genes such as the Tau locus and the microcephalin-1, implicated in brain aging and development, respectively. Variants of the latter genes found among present-day humans have been suggested to have come from Neandertals. The preliminary results suggest that Neandertals have contributed, at most, a very small fraction of the variation found in contemporary human populations.

Max-Planck-Gesellschaft

---

---

	How To Think Like a Neandertal by Thomas Wynn (Author), Frederick L. Coolidge (Author) There have been many books, movies, and even TV commercials featuring Neandertals--some serious, some comical. But what was it really like to be a Neandertal? How were their lives similar to or different from ours? In How to Think Like a Neandertal, archaeologist Thomas Wynn and psychologist Frederick L. Coolidge team up to provide a brilliant account of the mental life of Neandertals, drawing on the most recent fossil and archaeological remains. Indeed, some Neandertal remains are not fossilized, allowing scientists to recover samples of their genes--one specimen had the gene for red hair and, more provocatively, all had a gene called FOXP2, which is thought to be related to speech. Given the differences between their faces and ours, their voices probably sounded a bit...
	The Neandertal Enigma : Solving the Mystery of Modern Human Origins by James Shreeve (Author) In search of the truth about the Neanderthals, Shreeve takes readers on a prehistoric journey as he examines the scientific evidence and addresses the controversy surrounding their fate. He offers a fascinating theory of what might have allowed two equally human species to share a moment in evolution history, as well as what may have led to the triumph of one and the poignant disappearance of the other.
	The Neandertals: Changing the Image of Mankind by Erik Trinkaus (Author), Pat Shipman (Author) To one nineteenth-century scholar, their fierce, ridged brows were evidence of a "moral darkness" that set them irrevocably apart from human beings. Some commentators accused them of cannibalism. Yet by the 1970s the Neandertals were being hailed as "the first flower people" and praised for their apparent compassion and religious piety. The story of how scientists could come to such divergent conclusions about a set of bones unearthed in Germany in 1856 unfolds with irresistible detail in this enthralling book. Even as The Neandertals assesses the identity, kinship, and character of our possible ancestors, it casts a wry eye on the modern Homo sapiens who have embraced or disavowed them and illuminates the peculiar way in which even science is shaped by human needs and...
	Reassessing Paleolithic Subsistence: The Neandertal and Modern Human Foragers of Saint-Césaire by Dr Eugène Morin (Author) The contribution of Neandertals to the biological and cultural emergence of early modern humans remains highly debated in anthropology. Particularly controversial is the long-held view that Neandertals in Western Europe were replaced 30,000 to 40,000 years ago by early modern humans expanding out of Africa. This book contributes to this debate by exploring the diets and foraging patterns of both Neandertals and early modern humans. Eugène Morin examines the faunal remains from Saint-Césaire in France, which contains an exceptionally long and detailed chronological sequence, as well as genetic, anatomical, and other archaeological evidence to shed new light on the problem of modern human origins.
	The Neandertals: Of Skeletons, Scientists, and Scandal by Erik Trinkaus (Author) To one nineteenth-century scholar, their fierce, ridged brows were evidence of a "moral darkness" that set them irrevocably apart from human beings. Some commentators accused them of cannibalism. Yet by the 1970s the Neandertals were being hailed as "the first flower people" and praised for their apparent compassion and religious piety. The story of how scientists could come to such divergent conclusions about a set of bones unearthed in Germany in 1856 unfolds with irresistible detail in this enthralling book. Even as The Neandertals assesses the identity, kinship, and character of our possible ancestors, it casts a wry eye on the modern Homo sapiens who have embraced or disavowed them and illuminates the peculiar way in which even science is shaped by human needs and biases.
	Neandertals: A Prehistoric Puzzle (Discovery!) by Yvette La Pierre (Author) When the first Neandertal skeleton was discovered nearly 150 years ago, scientists presented the race as barely developed brutes. But recent findings indicate that Neandertals made complex tools, organized group hunts, cared for their sick and injured, and buried their dead. How advanced were they? How and why did they disappear? Did they live side-by-side with modern humans?
	Neandertals and Modern Humans in Western Asia by Takeru Akazawa (Editor), Kenichi Aoki (Editor), Ofer Bar-Yosef (Editor) In this fascinating volume, the Middle Paleolithic archaeology of the Middle East is brought to the current debate on the origins of modern humans. These collected papers gather the most up-to-date archaeological discoveries of Western Asia - a region that is often overshadowed by African or European findings - but the only region in the world where both Neandertal and early modern human fossils have been found. The collection includes reports on such well known cave sites as Kebara, Hayonim, and Qafzeh, among others. The information and interpretations available here are a must for any serious researcher or student of anthropology or human evolution.
	Spirit Fire: Neandertals Book Two by Glen Stott (Author) The second book in a trilogy about the interaction of Neanderthals and Cro-Magnons, Spirit Fire is an epic adventure that sweeps across pre-historic Europe, Asia, and Alaska, as the man who invented war embarks on a quest to conquer the world. Rumors of unusual people living in caves far to the east of the warriors’ land attract warrior leader Warlog. His shaman, Rayloc, fears the strangers are really Droglits, servants of evil from deep in the earth who have come to destroy his way of life. In the east, Sotif, History Man of The Alliance between Earth People and Sun People, tries to guard his culture against changes that could induce Mother Earth to withdraw her blessings. But Warlog is intent upon breaking The Alliance by subjugating the Sun People and destroying the Earth...
	Neandertal: Die Geschichte geht weiter (German Edition) by Ralf Schmitz (Author), Jürgen Thissen (Author) Im Sommer 1997 führten die Archäologen Dr. Ralf W. Schmitz und Dr. Jürgen Thissen vom Rheinischen Amt für Bodendenkmalpflege am Ufer der Düssel Sondagen durch mit dem Ziel, den Aushub der kleinen Feldhofer Grotte - jener Höhle, in der 1856 der Neandertaler entdeckt worden war - zu lokalisieren. Gestützt auf altes Kartenmaterial und die Ergebnisse von Sondagen aus dem Jahre 1984 gelang ihnen eine detektivische Glanzleistung. Etwa 50 Meter von der alten Untersuchungsstelle entfernt konnten sie Reste lehmiger Höhlenfüllungen mit Besiedlungsspuren des eiszeitlichen Menschen entdecken. Dieser Aushub war von Steinbrucharbeitern 1856 vor der Sprengung der Kalkfelsen aus den Höhlen herausgeschaufelt und am Düsselufer aufgehäuft worden. Sprengschutt überdeckte die Abraumhaufen und hat...
	The Geography of Neandertals and Modern Humans in Europe and the Greater Mediterranean (Peabody Museum Bulletin 8) by Ofer Bar-Yosef (Editor), David Pilbeam (Editor) During the Middle Paleolithic, various populations ancestral to modern Hone sapiens inhabited Africa, while Europe was homeland to the Neandertals. Recent archaeological investigations have provided data showing that the abrupt transition from the Middle to the Upper Neolithic, during which these populations met and interacted, was a fast-moving period of change for both groups. In this volume, the expansion of modern humans and their impact on the populations of Neandertals in Europe, Western Asia, and Northern Africa is discussed in depth, with particular focus on the lithic industries of the late Middle and early Upper Paleolithic.