Genetics

Cracking the Neanderthal code

Two new studies show how to sequence the genome of an extinct species

Recreating dinosaurs may be the stuff of science fiction - but scientists have for some years been able to extract information from the remains

of species that no longer walk the Earth. Unfortunately this evidence is often in the form of tiny, jumbled snippets and it is frequently contaminated. Two new ways to patch the oddments together and distinguish genuine from false information are reported this week.

Scientists intend to use the techniques to produce the complete genome of a creature that is not only extinct but also happens to be their closest relative.

When humans first emerged as a species they shared the planet with many types of ape. The fossilised remains of one such species were discovered in the Neander Valley in Germany some 150 years ago.Neanderthal

man, as the species has come to be called, was shorter and stockier than humans. The evidence suggests that he was a cousin rather than an ancestor of humanity. Mitochondrial DNA extracted from the bones of Neanderthals does not resemble DNA from any known modern humans, so scientists have concluded

that there was no interbreeding between the two, which is what distinguishes one species from another.

nevertheless Neanderthal man is thought to be man's closest relative. If scientists could recreate his genome, the strings of billions of letters that spell our how to build and run a Neanderthal, they would be able to pinpoint the precise difference between the two species. Moreover, by comparing the two genomes, they could see what makes people human. Until now many researchers have argued that it would be impossible to sequence the entire genome of an extinct creature because the samples are so degraded. How could so many tiny fragments fo DNA be pieced together? And how would it be possible to check whether the jigsaw pieces had been assembled correctly?

Never say never

Two teams of researchers appear to have solved these probles. The first held by Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, has managed to sequence more than 1m letters of Neanderthal DNA. Although in total the team has unearthed far fewer letters(some 65,000) than its competitors, its discoveries are significant because they focus on specific genes: that is strings of DNA that are several thousand letters long.

The technology employed by Dr Paabo and his colleagues is extraordinary because it is 100 times faster than previous techniques. The researchers used "pyro sequencing", a process which breaks up the DNA into short chunks and then shakes them up in a mixture of water, a special silicone-based oil, a large quantity of tiny plastic balls and chemicals capable of duplicating DNA. This mixture is then applied to a tiny chip with 1m wells in it. Get the conditions right and the result is that the wells each contain just one sort of DNA molecule. These can be analysed by a technique that uses fluorescence to read the sequences of the letters that compose the molecules. It is fast because many batches can be done at the same time and the whole process can be automated.

What is more, the method can make sense of the short fragments of DNA that are all that remain in the crumbling bones of a Neanderthal specimen. This was no mean feat: the team tested more than 70 bones and found just one, a thigh bone found in a cave in Vindija,Croatia, that was in good enough condition for the technique to succeed.To reassemble the resulting pieces of information into a coherent picture, Dr Paabo and his colleagues compared their pieces with the human genome, which has been fully sequenced.By mapping stretches of Neanderthal DNA to human equivalent, the researchers were able to complete bits of the jigsaw.

Dr. Rubin and his colleagues used what is called a "metagenomic" approach. This has one great advantage: it can be used to target specific areas of interest. The researchers propagated individual DNA fragments in the traditional way, in bacteria, to create a gene library; they also developed a method for pulling out specific sequences from the library, providing an easy way to study any gene of interest. They found 20 Neanderthal sequences that are similar to those of humans and concluded that Neanderthals and humans are likely to be at least 99.5% identical, genetically speaking.

The researchers propose to sequence the genome six times, allowing them to identify any mistakes. On its way to being fully decoded the human genome was sequenced , on average, ten times.