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.
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. …
DNA signatures found in present-day Europeans and Asians, but not in Africans
Researchers have produced the first whole genome sequence of the 3 billion letters in the Neanderthal genome, and the initial analysis suggests that up to 2 percent of the DNA in the genome of present-day humans outside of Africa originated in Neanderthals or in Neanderthals’ ancestors.
The international research team, which includes researchers from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, reports its findings in the May 7, 2010, issue of Science.
The current fossil record suggests that Neanderthals, or Homo neanderthalensis, diverged from the primate line that led to present-day humans, or Homo sapiens, some 400,000 years ago in Africa. Neanderthals migrated north into Eurasia, where they became a geographically isolated group that evolved independently from the line that became modern humans in Africa. They lived in Europe and western Asia, as far east as southern Siberia and as far south as the Middle East.
Approximately 30,000 years ago, Neanderthals disappeared. That makes them the most recent, extinct relative of modern humans, as both Neanderthals and humans share a common ancestor from about 800,000 years ago. Chimpanzees diverged from the same primate line some 5 million to 7 million years ago
The researchers compared DNA samples from the bones of three female Neanderthals who lived some 40,000 years ago in Europe to samples from five present-day humans from China, France, Papua New Guinea, southern Africa and western Africa. This provided the first genome-wide look at the similarities and differences of the closest evolutionary relative to humans, and maybe even identifying, for the first time, genetic variations that gave rise to modern humans.
“This sequencing project is a technological tour de force,” said NHGRI Director Eric D. Green, M.D., Ph.D. “You must appreciate that this international team has produced a draft sequence of a genome that existed 400 centuries ago. Their analysis shows the power of comparative genomics and brings new insights to our understanding of human evolution.”
The Neanderthal DNA was removed from bones discovered at Vindija Cave in Croatia and prepared in the clean room facility of the Max Planck Institute for Evolutionary Anthropology (http://www.eva.mpg.de/english/index.htm) in Leipzig, Germany, to prevent contamination with contemporary DNA. The Max Planck group is led by their Department of Evolutionary Genetics Director Svante Pääbo, Ph.D., a well-known pioneer in Neanderthal genome research. The team deposited the Neanderthal genome sequence in the publicly available NIH genetic sequence database GenBank (http://www.ncbi.nlm.nih.gov/genbank/).
To understand the genomic differences between present-day humans and Neanderthals, the researchers compared subtle differences in the Neanderthal genome to the genomes found in DNA from the five people, as well as to chimpanzee DNA. An analysis of the genetic variation showed that Neanderthal DNA is 99.7 percent identical to present-day human DNA, and 98.8 percent identical to chimpanzee DNA. Present-day human DNA is also 98.8 percent identical to chimpanzee.
“The genomic calculations showed good correlation with the fossil record,” said coauthor Jim Mullikin, Ph.D., an NHGRI computational geneticist and acting director of the NIH Intramural Sequencing Center (http://www.nisc.nih.gov/). “According to our results, the ancestors of Neanderthals and modern humans went their separate ways about 400,000 years ago.”