BioEd Online

Pop fiction such as Jurassic Park has fuelled the idea that it is easy to extract genetic material from ancient remains. Although this is not the case, technology has now been devised to reconstruct the genomes of animals who lived millions of years ago.

Scientists cannot reliably recover DNA that is more than 50,000 years old. To investigate older sequences, researchers have to rely on computer programs that infer backwards from present-day animals.

But this approach has been limited in the past because there was not enough information available about modern genomes. And the algorithms used by such programs also had limitations: for example, they considered only one type of genetic mutation, known as substitution.

Now that mammalian species such as the human and mouse have had their genomes sequenced, and others such as the chicken and chimp are in the pipeline, there are plenty of sequence data available for studying these animals. And computer algorithms have been developed that are able to take into account other types of genetic mutation, such as additions and deletions.

Next generation

David Haussler of the University of California, Santa Cruz, and his colleagues decided it was time to put 'computational genomics' to the test. To assess their method, they created a hypothetical portion of ancestral mammalian DNA and let a computer model simulate the process of evolution, to generate sequences for its descendants.

Then they made their algorithm work backward from these descendants, to see if it could recreate the original ancestor. The ancestor the algorithm came up with had a sequence that was 98% accurate, they report this week in Genome Research¹.

The researchers attribute the success of their technique to the fact that mammalian genomes are generally very diverse. This makes any regions of DNA they share in common stand out more clearly. "It's a pleasant surprise that mammals diversified so rapidly into different lineages that have surviving members today," says Haussler. "It gives us this opportunity to uncover the past."

Back to the future

Once they had determined that the technique was accurate, the researchers used the algorithm on DNA sequences from real mammals.

The team took 19 modern mammals, including the pig, human and rat, and used the algorithm to work out the genome of their common ancestor, thought to be a shrew-like animal that lived more than 70 million years ago. They focused on a small region of the genome that codes for ten genes.

One surprising result was that, compared with the ancestral sequence, the human sequence has lost only 11% of the genetic units called bases, whereas in rodents around 39% have been deleted. The researchers think this is probably because rats and similar animals go through generations more quickly, so they accumulate mutations faster.

The comparison with the recreated ancestral DNA should give other researchers clues about how and when the various descendants branched off. "You can see what special twists made each species different," says Haussler.

The team hopes to expand the study to look at the rest of the mammalian genome. The ultimate aim is "to understand in detail the history of every base in the human genome," says Haussler.