Neanderthal DNA lives on ... in some of us

[Savwafair2012 Profile]

Geneticist Svante Pääbo, leader of an international team of researchers who
decoded the Neanderthal genome, holds the skull of a Neanderthal.


The first rough draft of the Neanderthals' genome suggests that they interbred with our own species - but only enough to leave a tiny mark on the genetic code of humans from outside Africa.

"The Neanderthals are not totally extinct," said Svante Pääbo, a geneticist at Germany's Max Planck Institute for Evolutionary Anthropology. "In some of us they live on, a little bit."

Pääbo is the leader of an international team of researchers who worked for four years to extract the genetic code from half a gram of ground-up Neanderthal bone, taken from three separate specimens. The resulting draft sequence, which represents about 60 percent of the entire genome, is unveiled in this week's issue of the journal Science.

The results shed light on the evolution of our own species, Homo sapiens, as well as on the genetic heritage of now-extinct Homo neanderthalensis. When researchers compared the detailed Neanderthal code with that of five modern-day humans from different areas of the world, they found overwhelming similarities. But they also found some scientifically significant differences.

Genetic sequences from the three non-African modern individuals (from Papua New Guinea, China and France) were statistically more likely to be similar to Neanderthals than the sequences from southern Africa and West Africa. That suggests that some interbreeding took place after early humans spread out from Africa, most likely in the Middle East 50,000 to 100,000 years ago, Pääbo and his colleagues said.

But they stressed that it wasn't all that much interbreeding. Between 1 and 4 percent of the human genome appears to have come from Neanderthals, statistically speaking. The researchers could find no specific string of code could be definitively traced back to them across the full sample. They could not point to any trait that we have inherited specifically from Neanderthals.

Ian Tattersall, an anthropologist at the American Museum of Natural History who was not involved in the research, said the study meshes with earlier findings about the relationship between the two species. Just last month, for example, yet another team of researchers reported similar statistical signs of Neanderthal DNA in samples from modern humans.

"I don't think it changes the picture we already had, that Neanderthals and Homo sapiens were functionally individuated entities," Tattersall told me. "This is what species are about. There may have been a bit of Pleistocene hanky-panky, but nothing that left a clear biological mark on either party."

A tangled tale
Untangling our connection to Neanderthals is tricky on several counts. First, you have to get the Neanderthal DNA.

The species is reflected in the European fossil record as far back as 400,000 years ago, and scientists believe that Neanderthals co-existed with us Homo sapiens types until about 30,000 years ago. Did we kill them off? Were they assimilated into our species' gene pool? Or were they simply ill-suited to cope with changing conditions on Earth?

For whatever reason, the Neanderthals left behind a relatively scant record. To conduct their genetic study, Pääbo and his colleagues checked out 21 Neanderthal bone samples that were recovered from Croatia's Vindija Cave. Three of the bones, thought to date back to around 40,000 years ago, were selected for detailed DNA analysis.

Tiny amounts of powder were extracted from the interiors of the bones with a sterile dental drill, processed with chemicals and run through DNA-sequencing machines. An analysis of the DNA showed that 95 to 99 percent of it was from other organisms - for example, microbes that colonized the bones after the Neanderthals died. But the researchers used special enzymes to separate the signature of Neanderthal DNA from that of microbial (and human) contamination.

Even though the Neanderthal DNA was broken up into small pieces, the researchers sequenced 3 billion base pairs and completed about 60 percent of the genome's jigsaw puzzle.

Humans vs. Neanderthals
Decoding the genome was only part of the job. Comparing that genome with our own genetic code was just as tricky. Neanderthals and the human species are thought to have diverged only 500,000 years ago, which means the two species are close cousins in anthropological terms. In fact, if you compared a particular area of the Neanderthal genome with the corresponding genetic code in a single modern human, there's a chance you'd find more similarities than you'd see between two modern humans.

When Pääbo started the project, he didn't think he'd find any evidence of "gene flow" between ancient Neanderthals and humans. After all, an earlier study involving a different kind of genetic code known as mitochondrial DNA showed no such intermixing. "I was probably biased really in the direction that it would not have happened," Pääbo said.

But when the comparison came back with the five modern humans, and the researchers found more similarities between the Neanderthal genome and the non-African genomes, that was a big hint that Neanderthals interbred with ancient humans after they emerged from Africa. "At first I thought it was some kind of statistical fluke," Pääbo said.

The researchers rechecked their results, looked for alternate explanations, and went so far as to do yet another comparison with genomics pioneer Craig Venter's personal code. But the link between Neanderthals and non-Africans held up.

"This was really a surprise to us," said Harvard geneticist David Reich, one of the co-authors of the study.

Case closed?
The question over whether ancient humans ever "did it" with Neanderthals now appears to be resolved, but the draft genome raises more questions that are just as deep. For example, what traits did humans develop that gave them an evolutionary edge over Neanderthals? The researchers found some intriguing clues:

Five genes stood out as different in Neanderthals and modern humans. One of them has to do with how sperm cells whip their tails around. Another relates to wound-healing. Yet another builds a protein for the skin, sweat glands and hair roots. "It's tantalizing to think that the skin changed, but the biological implication of that is not at all clear yet," Pääbo said.


Several genes showed evidence of positive selection in humans as opposed to Neanderthals - including genes linked to schizophrenia, autism and Down syndrome. "This suggests that some of the genes that were positively selected may have had to do with cognitive development. ... It doesn't suggest that Neanderthals had no autism, or that they were more similar to people with autism," Pääbo said.


The researchers also focused on a gene that was linked to development of the frontal part of the skull, the shoulder bone and ribcage. Those are anatomical features where Neanderthals and humans differ, so the researchers said it was a "reasonable hypothesis" that that particular gene, RUNX2, "was of importance in the origin of modern humans."
Researchers are continuing to analyze the Neanderthal genetic data, and they expect to get a clearer picture of the species distinctions as time goes on.

Right now, the coverage of the genome is 1.3x, which means an individual DNA base pair was checked only 1.3 times on average. Pääbo said "our goal for the next two to three years is to come somewhere between 10 and 20x coverage," which would be comparable to the accuracy for a typical human genome. He estimated the cost of the project so far at 2 million to 3 million euros ($2.5 million to $3.8 million), but added that "it will be a lot cheaper to now go on."

Tattersall said the research team's first draft was "a remarkable achievement, and something they should be congratulated for." And he expected that there would be even more remarkable revelations ahead.

"This is the beginning of the story," he told me, "not the end of it."

http://cosmiclog.msnbc.msn.com/archive/ ... ?gt1=43001

[Eaganthorn Profile]

In some of us, more than others. I was looking at the guy who set the times square bomb and would swear that he got a triple dose of Neanderthal DNA, if not a little more.

If he hadn't gone with the terrorist thing, he could have been selling car insurance and saving everybody 15% or more.

[Brothers Profile]

Has anyone gone to the beach and see some of those men there???. Some of them looked like big hairy beast and vile looking. Those are your Neanderthals.

[Harbin Profile]

I WAS going to make a crack about French Canadian women, not ALL just a very few, but I'm not going to say ANYTHING about my casual observations.

IThere needs to be considerably more peer review on this methinks.

[zionslion Profile]

im waiting for pindz to post something about how jews are the ones who got the dna

[Eaganthorn Profile]

I WAS going to make a crack about French Canadian women, not ALL just a very few, but I'm not going to say ANYTHING about my casual observations.

IThere needs to be considerably more peer review on this methinks.

LOL
>eaganthorn bites lip, a small drop of blood runs down his chin<

[Kingz Profile]

Neanderthal Genome Yields Insights Into Human Evolution and Evidence of Interbreeding With Modern Humans
ScienceDaily (May 6, 2010)

After extracting ancient DNA from the 40,000-year-old bones of Neanderthals, scientists have obtained a draft sequence of the Neanderthal genome, yielding important new insights into the evolution of modern humans.


Richard E. (Ed) Green, a computational biologist in the Baskin School of Engineering at UC Santa Cruz, has been coordinating the Neanderthal Genome Project since 2005. In this photo he is holding replicas of the bones from which Neanderthal DNA was extracted for genome sequencing and a Neanderthal skull. (Credit: Photo by Jim MacKenzie)

Among the findings, published in the May 7 issue of Science, is evidence that shortly after early modern humans migrated out of Africa, some of them interbred with Neanderthals, leaving bits of Neanderthal DNA sequences scattered through the genomes of present-day non-Africans.

"We can now say that, in all probability, there was gene flow from Neanderthals to modern humans," said the paper's first author, Richard E. (Ed) Green of the University of California, Santa Cruz.

Green, now an assistant professor of biomolecular engineering in the Baskin School of Engineering at UC Santa Cruz, began working on the Neanderthal genome as a postdoctoral researcher at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Svante Pääbo, director of the institute's genetics department, leads the Neanderthal Genome Project, which involves an international consortium of researchers. David Reich, a population geneticist at the Broad Institute of MIT and Harvard, also played a leading role in the new study and the ongoing investigation of the Neanderthal genome.

"The Neanderthal genome sequence allows us to begin to define all those features in our genome where we differ from all other organisms on the planet, including our closest evolutionary relative, the Neanderthals," Pääbo said.

The researchers identified a catalog of genetic features unique to modern humans by comparing the Neanderthal, human, and chimpanzee genomes. Genes involved in cognitive development, skull structure, energy metabolism, and skin morphology and physiology are among those highlighted in the study as likely to have undergone important changes in recent human evolution.

"With this paper, we are just scratching the surface," Green said. "The Neanderthal genome is a goldmine of information about recent human evolution, and it will be put to use for years to come."

Neanderthals lived in much of Europe and western Asia before dying out 30,000 years ago. They coexisted with humans in Europe for thousands of years, and fossil evidence led some scientists to speculate that interbreeding may have occurred there. But the Neanderthal DNA signal shows up not only in the genomes of Europeans, but also in people from East Asia and Papua New Guinea, where Neanderthals never lived.

"The scenario is not what most people had envisioned," Green said. "We found the genetic signal of Neanderthals in all the non-African genomes, meaning that the admixture occurred early on, probably in the Middle East, and is shared with all descendants of the early humans who migrated out of Africa."

The study did not address the functional significance of the finding that between 1 and 4 percent of the genomes of non-Africans is derived from Neanderthals. But Green said there is no evidence that anything genetically important came over from Neanderthals. "The signal is sparsely distributed across the genome, just a 'bread crumbs' clue of what happened in the past," he said. "If there was something that conferred a fitness advantage, we probably would have found it already by comparing human genomes."

The draft sequence of the Neanderthal genome is composed of more than 3 billion nucleotides--the "letters" of the genetic code (A, C, T, and G) that are strung together in DNA. The sequence was derived from DNA extracted from three Neanderthal bones found in the Vindiga Cave in Croatia; smaller amounts of sequence data were also obtained from three bones from other sites. Two of the Vindiga bones could be dated by carbon-dating of collagen and were found to be about 38,000 and 44,000 years old.

Deriving a genome sequence--representing the genetic code on all of an organism's chromosomes--from such ancient DNA is a remarkable technological feat. The Neanderthal bones were not well preserved, and more than 95 percent of the DNA extracted from them came from bacteria and other organisms that had colonized the bone. The DNA itself was degraded into small fragments and had been chemically modified in many places.

The researchers had to develop special methods to extract the Neanderthal DNA and ensure that it was not contaminated with human DNA. They used new sequencing technology to obtain sequence data directly from the extracted DNA without amplifying it first. Although genome scientists like to sequence a genome at least four or five times to ensure accuracy, most of the Neanderthal genome has been covered only one to two times so far.

The draft Neanderthal sequence is probably riddled with errors, Green said, but having the human and chimpanzee genomes for comparison makes it extremely useful despite its limitations. Places where humans differ from chimps, while Neanderthals still have the ancestral chimp sequence, may represent uniquely human genetic traits. Such comparisons enabled the researchers to catalog the genetic changes that have become fixed or have risen to high frequency in modern humans during the past few hundred thousand years.

"It sheds light on a critical time in human evolution since we diverged from Neanderthals," Green said. "What adaptive changes occurred in the past 300,000 years as we were becoming fully modern humans? That's what I find most exciting. Right now we are still in the realm of identifying candidates for further study."

The ancestral lineages of humans and chimpanzees are thought to have diverged about 5 or 6 million years ago. By analyzing the Neanderthal genome and genomes of present-day humans, Green and his colleagues estimated that the ancestral populations of Neanderthals and modern humans separated between 270,000 and 440,000 years ago.

The evidence for more recent gene flow between Neanderthals and humans came from an analysis showing that Neanderthals are more closely related to some present-day humans than to others. The researchers looked at places where the DNA sequence is known to vary among individuals by a single "letter." Comparing different individuals with Neanderthals, they asked how frequently the Neanderthal sequence matches that of different humans.

The frequency of Neanderthal matches would be the same for all human populations if gene flow between Neanderthals and humans stopped before human populations began to develop genetic differences. But that's not what the study found. Looking at a diverse set of modern humans--including individuals from Southern Africa, West Africa, Papua New Guinea, China, and Western Europe--the researchers found that the frequency of Neanderthal matches is higher for non-Africans than for Africans.

According to Green, even a very small number of instances of interbreeding could account for these results. The researchers estimated that the gene flow from Neanderthals to humans occurred between 50,000 and 80,000 years ago. The best explanation is that the admixture occurred when early humans left Africa and encountered Neanderthals for the first time.

"How these peoples would have interacted culturally is not something we can speculate on in any meaningful way. But knowing there was gene flow is important, and it is fascinating to think about how that may have happened," Green said.

The researchers were not able to rule out one possible alternative explanation for their findings. In that scenario, the signal they detected could represent an ancient genetic substructure that existed within Africa, such that the ancestral population of present-day non-Africans was more closely related to Neanderthals than was the ancestral population of present-day Africans. "We think that's not the case, but we can't rule it out," Green said.

The researchers expect many new findings to emerge from ongoing investigations of the Neanderthal genome and other ancient genetic sequences. Pääbo's group recently found evidence of a previously unknown type of hominid after analyzing DNA extracted from what they had thought was a Neanderthal finger bone found in Siberia. Green is also taking part in that continuing investigation.

Journal Reference:
1. Richard E. Green, Johannes Krause, Adrian W. Briggs, Tomislav Maricic, Udo Stenzel, Martin Kircher, Nick Patterson, Heng Li, Weiwei Zhai, Markus Hsi-Yang Fritz, Nancy F. Hansen, Eric Y. Durand, Anna-Sapfo Malaspinas, Jeffrey D. Jensen, Tomas Marques-Bonet, Can Alkan, Kay Prüfer, Matthias Meyer, Hernán A. Burbano, Jeffrey M. Good, Rigo Schultz, Ayinuer Aximu-Petri, Anne Butthof, Barbara Höber, Barbara Höffner, Madlen Siegemund, Antje Weihmann, Chad Nusbaum, Eric S. Lander, Carsten Russ, Nathaniel Novod, Jason Affourtit, Michael Egholm, Christine Verna, Pavao Rudan, Dejana Brajkovic, Zeljko Kucan, Ivan Gusic, Vladimir B. Doronichev, Liubov V. Golovanova, Carles Lalueza-Fox, Marco de la Rasilla, Javier Fortea, Antonio Rosas, Ralf W. Schmitz, Philip L. F. Johnson, Evan E. Eichler, Daniel Falush, Ewan Birney, James C. Mullikin, Montgomery Slatkin, Rasmus Nielsen, Janet Kelso, Michael Lachmann, David Reich, and Svante Pääbo. A Draft Sequence of the Neandertal Genome. Science, 2010; 328 (5979): 710-722 DOI:
http://www.sciencemag.org/cgi/content/a ... 8/5979/710
http://www.ucsc.edu/public/

http://www.sciencedaily.com/releases/20 ... 141549.htm