July 21, 2006

Can We Recover The Neaderthal Genome

This is going back into pre-history -- and may be another thing I pass on to my students during the first week or two of school, as we deal with the earliest history of humanity. There is just so much we don't know, so anything we can find out is exciting.

Researchers in Germany said Thursday that they planned to collaborate with an American company in an effort to reconstruct the genome of Neanderthals, the archaic human species that occupied Europe from 300,000 years ago to 30,000 years ago until being displaced by modern humans.

Long a forlorn hope, the sequencing, or decoding, of Neanderthal DNA suddenly seems possible because of a combination of analytic work on ancient DNA by Svante Paabo, of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and a new method of DNA sequencing developed by a Connecticut company, 454 Life Sciences.

The initial genome to be decoded comes from 45,000-year-old Neanderthal bones found in Croatia, though bones from other sites may be analyzed later. Because the genome must be kept in constant repair and starts to break up immediately after the death of the cell, the material surviving in Neanderthal bones exists in tiny fragments 100 or so DNA units in length. As it happens, this is just the length that works best with the 454 machine, which is also able to decode vast amounts of DNA at low cost.

Recovery of the Neanderthal genome, in whole or in part, would be invaluable for reconstructing many events in human prehistory and evolution. It would help address such questions as whether Neanderthals and humans interbred, whether the archaic humans had an articulate form of language, how the Neanderthal brain was constructed, if they had light or dark skin, and the total size of the Neanderthal population.

And they only have to sequence 3 billion bits of Neanderthal DNA to do it, while separating out the DNA of human handlers of the bones and the various bacteria that have entered teh bones over the course of tens of thousands of years.

But they do have some areas with which to start.

The researchers’ hope is to recover the entire sequence of the Neanderthal genome, but that will depend on whether they can recover enough DNA. From sampling so far, no particular gaps in the sequence are apparent. “We are hitting all the chromosomes and getting good coverage,” Dr. Egholm said. If no single specimen yields a full sequence, the genome might be recovered by combining DNA from several individuals.

One of the most important results that researchers are hoping for is to discover, from a three-way comparison of chimp, human and Neanderthal DNA, which genes have made humans human. The chimp and human genomes differ at just 1 percent of the sites on their DNA. At this 1 percent, Neanderthals resemble humans at 96 percent of the sites, to judge from the preliminary work, and chimps at 4 percent. Analysis of these DNA sites, at which humans differ from the two other species, will help understand the evolution of specifically human traits “and perhaps even aspects of cognitive function,” Dr. Paabo said.

The degree of resemblance between humans and Neanderthals is fiercely debated by archaeologists, and even issues like whether Neanderthals had language have not been resolved. Dr. Paabo believes that genetic analysis is the best hope of doing so. He has paid particular attention to a gene known as FOXP2, which from its mutated forms in people seems to be involved in several advanced aspects of language.

A longstanding dispute among archaeologists is whether the modern humans who first entered Europe 45,000 years ago, ultimately from Africa, interbred with the Neanderthals or forced them into extinction. Interbreeding could have been genetically advantageous to the incoming humans, says Bruce Lahn, a geneticist at the University of Chicago, because the Neanderthals were well adapted to the cold European climate — the last ice age had another 35,000 years to run — and to local diseases.

And that plays out in textbooks. My old book indicated tehre was no relationship, my new one that there was not, and much current research comes down in the middle. The recovery of the full genome might well lay that question to rest, along with the question of interbreeding.

I won't telll you what lies at the end of the article -- but it raises all sorts of moral/ethical questions that are fascinating to think about.

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