Neanderthals Had Important Speech Gene, DNA Evidence Shows

from The New York Times

By NICHOLAS WADE
Published: October 19, 2007

Neanderthals, an archaic human species that dominated Europe until the arrival of modern humans some 45,000 years ago, possessed a critical gene known to underlie speech, according to DNA evidence retrieved from two individuals excavated from El Sidron, a cave in northern Spain.

The new evidence stems from analysis of a gene called FOXP2 which is associated with language. The human version of the gene differs at two critical points from the chimpanzee version, suggesting that these two changes have something to do with the fact that people can speak and chimps cannot.

The genes of Neanderthals seemed to have passed into oblivion when they vanished from their last refuges in Spain and Portugal some 30,000 years ago, almost certainly driven to extinction by modern humans. But recent work by Svante Paabo, a biologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, has made it clear that some Neanderthal DNA can be extracted from fossils.

Dr. Paabo, Dr. Johannes Krause and Spanish colleagues who excavated the new bones say they have now extracted the Neanderthal version of the relevant part of the FOXP2 gene. It is the same as the human version, they report in today's issue of Current Biology.

Because many other genes are also involved in the faculty of speech, the new finding suggests but does not prove that Neanderthals had human-like language.

"There is no reason to think Neanderthals couldn't speak like humans with respect to FOXP2, but obviously there are many other genes involved in language and speech," Dr. Paabo said.

The human version of the FOXP2 gene apparently swept through the human population before the Neanderthal and modern human lineages split apart some 350,000 years ago.

But until more is known about what FOXP2 does in the brain, it is hard to know what powers were conferred by the sweep, said Gary Marcus, a psychologist at New York University who has written about the evolution of language. "Perhaps Neanderthals had some rudiments of language, but then again, maybe not."

A new strain of mice may have something to say about how FOXP2 affects language. Dr. Paabo has developed mice whose FOXP2 genes have been replaced with the human version. The mice have extra neuronal connections in their brains and make an unusual sound. "There seems to be a change in vocalization — they squeak in a different way," Dr. Paabo said. "But there are no obvious differences in behavior; in most ways they are normal mice."

The ability to fish out a specific gene of interest from the Neanderthal genome is a remarkable technical feat, if that has indeed been achieved. The results "have the potential to become a keystone in our understanding of human evolution," wrote an anonymous referee who reviewed Dr. Paabo's report for Current Biology.

The study of human evolution may take a giant leap forward if Dr. Paabo should recover the entire Neanderthal genome, at least in draft form, a feat he said he hopes to accomplish by next year.

But two sudden clouds have overshadowed this grand prospect. One is that the new finding about FOXP2 sharply contradicts an earlier result Dr. Paabo announced five years ago.

Surveying the human version of FOXP2 in populations around the world, Dr. Paabo found in 2002 that everyone had essentially the same version of the gene. This happens when a new version of a gene confers such a survival advantage that it sweeps through the population. This sweep had occurred sometime within the last 200,000 years, Dr. Paabo and colleagues reported in an article in Nature.

That date supported a proposal by Richard Klein of Stanford University, based on archaeological evidence, that the modern human population had undergone some neurological change around 50,000 years ago, which enabled their populations to expand and emerge from Africa. The neurological change could have been the perfection of modern language, given that few evolutionary advances could be more valuable to a social species.

But Dr. Paabo's new report pushes back the language-related changes in FOXP2 to at least 350,000 years ago, the time that the Neanderthal and modern human lineages split, a date that no longer supports Dr. Klein's thesis.

Pushed by the referees of his new report to say why the old one was so wrong, Dr. Paabo told the editors of Current Biology that the calculations underlying the younger date were "not flawed but rely on assumptions that are necessary but also universally known to be oversimplifications of the reality."

While the assumptions may be well known to population geneticists, the caveats were not so clear to others. Dr. Klein said he was disappointed to have lost the genetic support from Dr. Paabo's work but had not changed his views. "The archaeological record suggests a major change in human behavior 50,000 years ago, and I think there is overwhelming evidence for that."

A second cloud over Dr. Paabo's work with Neanderthal DNA is the ever-present danger of contamination with the human DNA, especially since Dr. Paabo reports finding the human version of FOXP2 in Neanderthal bones.

Most fossil bones in museum collections, and even the chemical reagents used to analyze genetic material, are contaminated with human DNA. The contaminant often overwhelms the faint residual traces of Neanderthal DNA, which is hard at best to tell apart since the sequence of units is so similar.

Dr. Paabo has struggled valiantly to cope with the contamination issue. He has recovered the DNA sequence of Neanderthal mitochondrial DNA, a kind that is separate from the main genome in the cell's nucleus. By measuring the ratio of Neanderthal to human mitochondrial DNA, he can assess the degree of contamination in a sample.

Last year, to lay the groundwork for his analysis of the entire Neanderthal genome, Dr. Paabo decoded the sequence of many DNA fragments, and sent samples to a second laboratory for independent analysis.

This seemed a considerable feat. But in an article soon to be published in the journal PLoS Genetics, Jeffrey D. Wall and Sung K. Kim, two biologists at the University of California, San Francisco, say there are serious inconsistencies between the Neanderthal sequences Dr. Paabo published last year and those of the second laboratory, the Joint Genome Center Institute in Walnut Creek, Calif., headed by Edward M. Rubin.

The bottom line of their analysis is that Dr. Rubin's results were probably correct but Dr. Paabo's were highly contaminated with human DNA.

Dr. Paabo said he agreed in general with Drs. Wall and Kim's criticisms but noted the DNA extracts for both studies had been made in his clean room. He had then sent the samples for his own analysis to another laboratory, where the contamination could perhaps have occurred.

Dr. Paabo has now added extra safeguards, he said, such as tagging all the Neanderthal DNA extracted in his clean room.

For the FOXP2 analysis, he and his Spanish colleagues arranged for the bones to be excavated under sterile conditions and immediately frozen. In addition he analyzed the Neanderthal Y chromosome, showing it was very different from the human Y chromosome, and so provided a second test along with mitochondrial DNA to differentiate human and Neanderthal samples.

Dr. Wall said that in the new report Dr. Paabo and his colleagues "have been much more careful than they were before to control contamination, but I think it still remains a small possibility."

Why was such a striking result not presented to a better known journal such as Nature? Dr. Paabo replied that he had done so, but that "Nature rejected it without review. I was surprised."

FOXP2 first came to light in a large London family, half of whose members had subtle defects in their speech and understanding. Geneticists discovered that one of their two copies of FOXP2 was inactivated by a mutation.

The gene "provides an exciting molecular window into brain circuits that are important in speech," said Simon Fisher of Oxford University, a member of the team that discovered the FOXP2 mutation. Neanderthals and mice are not the only species contributing to the discussion. Echo-locating bats have a distinctive change in their FOXP2 gene at the same location as the human changes. Bats that don't hunt with sonar do not have these changes, a team of Chinese biologists, led by Gang Li and Shuyi Zhang of the East China Normal University in Shanghai, report in the current issue of the journal PLoS One.

This suggests FOXP2 may have evolved in bats to support the rapid motor sequencing involved in echolocation. Similar tweaking of FOXP2 could have occurred in the human lineage to support the fine motor sequencing involved in speech, Dr. Fisher said.

Original Article in Current Biology can be found here