Old bone helps crack Neanderthal DNA - interesting genetic news

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Old bone helps crack Neanderthal DNA

The genetic code of the long-dead species could shed light on the

evolution of humans, researchers say.

By Kaplan, Times Staff Writer

November 16, 2006

http://www.latimes.com/news/printedition/asection/la-sci-

neanderthal16nov16,1,3059902.story

Using a 38,000-year-old bone fragment found in a Croatian cave,

scientists have decoded a section of DNA from humanity's closest

related species — the long-extinct and enigmatic Neanderthal.

The reports, published concurrently today in the journals Nature and

Science, demonstrate the feasibility of squeezing genetic

information out of fossils — a new way of probing the ancient past

that until now has been glimpsed primarily through scattered bones

and artifacts.

" The sequence data will serve as a DNA time machine that will tell

us about biology and aspects of Neanderthals that we could never get

from their bones, " said Rubin, director of the genomics

division at Lawrence Berkeley National Laboratory and senior author

of the report in Science. Among other things, he said, it could shed

light on what caused Neanderthals to disappear from Europe about

30,000 years ago, shortly after modern humans moved into their

territory.

A complete Neanderthal genome would help scientists zero in on a

fundamental question: What makes humans human?

So far, researchers have sequenced about 1 million out of an

estimated 3 billion base pairs of the Neanderthal genome. They

expect it will take two years to complete a full draft.

" I'm super-excited about this project, " said S. Pollard,

an assistant professor at the UC Genome Center. She is looking

for genes important to human evolution by comparing them with genes

from chimpanzees, humans' closest living relative. " Neanderthals are

perfect [to study] because they are actually our closest relative

amongst all species that we know have ever lived. "

Even the preliminary sequences contain enough information to

calculate that Homo neanderthalis and Homo sapiens shared at least

99.5% of their DNA. The characteristics that make humans unique are

contained in the remaining 0.5%.

" This is just a toe in the water, but ultimately we'll be able to

identify genes in Neanderthals that seem to be important in people

and see if they have the same one, " said G. Klein, a

paleoanthropologist at Stanford University.

The genetic analysis was not precise enough to pinpoint the first

branching of the human and Neanderthal lineages.

Rubin's group estimated that the ancestors of humans and

Neanderthals began to genetically diverge about 706,000 years ago.

Another team publishing in Nature calculated the divergence occurred

516,000 years ago. The fossil record suggests a split time of

400,000 years ago.

These prehistoric beings gradually accumulated small genetic

mutations that were not outwardly visible at first but ultimately

resulted in separate species.

Fully evolved Neanderthals are thought to have arisen about 130,000

years ago, settling in Europe and western Asia. Modern Homo sapiens

emerged at roughly the same time in Africa.

As humans pushed their way into Eurasia 40,000 to 50,000 years ago,

they came in contact with their long-separated cousins. Within

10,000 to 20,000 years, the Neanderthals had disappeared.

One of the most hotly contested topics in paleoanthropology is

whether the two species interbred while they both inhabited Europe

and Asia. Scientists are eager to search for evidence of Neanderthal

genes in human DNA, and vice versa.

For example, Bruce Lahn, a professor of human genetics at the

University of Chicago, has proposed a controversial theory that

humans living among Neanderthals may have inherited a Neanderthal

gene called microcephalin that regulates brain size.

" Our biological evolution has actually benefited from mating with

our relative species that have gone extinct, " said Lahn, who wasn't

involved with the gene sequencing. " That's the exciting part. Parts

of them do live on in our genes. "

The DNA sequences decoded so far don't provide support for the

microcephalin theory, Rubin said, but neither have they ruled it out.

The Nature team found evidence that human males may have contributed

some of their DNA to the Neanderthal genome. The genes on the

Neanderthal's X chromosome include too many mutations found in the

human lineage to have occurred through chance, said Egholm

of 454 Life Sciences and coauthor of the Nature paper.

Svante Paabo, a pioneer in decoding ancient genomes, tested more

than 70 Neanderthal specimens over two years and found only one that

contained enough DNA to sequence. It came from part of a femur

discovered in Croatia's Vindija cave in 1980.

" This particular bone is rather small and uninteresting, " said Paabo

of the genetics department at the Max Planck Institute for

Evolutionary Anthropology in Leipzig, Germany, and senior author of

the Nature study. " It was sort of thrown in a big box of

uninformative bones in the museum in Zagreb and not handled very

much by people. More interesting bones have been extensively cleaned

and handled and thus tend to be much more contaminated. "

Examining a 100-milligram sample, Paabo's team found that more than

half of the DNA sequences were from bacteria that had been growing

on the bone for 38,000 years. A small amount was human DNA from

modern handlers of the bones, and the rest belonged to the

Neanderthal.

The researchers were able to clearly distinguish the Neanderthal DNA

because of telltale signs of chemical damage that occur over time.

In addition, the strings of DNA nucleotides — commonly known by the

chemical letters A, T, C and G — were typically only 50 or 60 base

pairs long, whereas samples from humans were usually at least twice

as long.

Paabo's group used a new technology developed by 454 Life Sciences

called pyrosequencing to decode about 1 million of the Neanderthal

base pairs. Using a different sequencing strategy, Rubin's team at

the U.S. Department of Energy Joint Genome Institute unraveled about

65,000 base pairs.

The sequencing of Neanderthal DNA is the biggest success so far in

the budding field of paleogenetics.

It began with Paabo in 1986, when he first retrieved DNA from

ancient mummies. In 1997 he extracted mitochondrial DNA from

Neanderthals. But that DNA, which is passed from mother to child,

contains far less information than the nuclear DNA reported on today.

" Twenty years ago there was a raging argument about whether

Neanderthals could be the ancestors of living human beings, " Klein

said. " Based on the fossils it seemed irresolvable. Then came the

mitochondrial DNA evidence. It showed that all living humans shared

a relatively recent ancestor in Africa from a time after

Neanderthals were extinct. Genetics settled that. "

For the new studies, Paabo and Rubin practiced their sequencing

techniques using genes from extinct cave bears, whose fossilized

remains are relatively abundant. Last summer, a group from the

University of Leipzig reported the discovery a well-known gene for

hair color in DNA from a 43,000-year-old mammoth bone. They

concluded that mammoth fur may have come in a variety of colors.

Some scientists have discussed the possibility of cloning the

mammoth or other prehistoric beasts. But Paabo and Rubin said

cloning a Neanderthal was inconceivable.

Efforts to clone human embryos using purified DNA have so far

failed, Paabo said, and it's even more farfetched " to imagine how

this would ever be done with something that's degraded, chemically

modified and mixed in with … bacterial DNA. "

Paabo also discounted the possibility of sequencing DNA from more

distant relatives, such as Homo erectus, which became extinct about

300,000 years ago.