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Last Updated: Wednesday, 1 December 2004, 00:54 GMT
Ancestor's DNA code reconstructed
DNA
The work should help us understand how humans are put together
Scientists have re-constructed part of the genetic code that would have existed in a common ancestor of placental mammals, including humans.

The creature, thought to be a nocturnal shrew-like animal, lived alongside dinosaurs about 75 million years ago.

The researchers used computer analysis to compare and contrast modern mammal genomes and then modelled a sequence that would have been common to all.

The work is reported in the December issue of the journal Genome Research.

The project was led by David Haussler, a Howard Hughes Medical Institute investigator at the University of California, Santa Cruz, US.

The 'Model T' of mammals

His team says the reconstruction effort is akin to drawing conclusions about the first car by observing the many different kinds of vehicles in use today.

If you gave me your genome and I changed just 1% of the bases, you wouldn't want to do that because just a few changes in important places would not be survivable
Mathieu Blanchette, McGill University
Although, the separate makes of automobile have changed and diversified over time, they share features that were present in their conceptual ancestor: four rubber tyres, a windshield, and an internal combustion engine, for example.

To rebuild the DNA sequence of the ancient mammalian ancestor, the researchers focused on a genome region called the CFTR locus, which includes the gene involved in cystic fibrosis in humans.

This region - which encompasses 10 genes and adjacent stretches of DNA, for a total of more than one million base-pairs or "letters" of genetic material - has been completely sequenced in many different mammals.

"We took all the sequences from the contemporary organisms and we compared them - we built what we call a multiple alignment," explained Mathieu Blanchette, currently at McGill University, Montreal, Canada.

"Based on the differences that we observed between the different mammals, we were able to work out, with pretty good accuracy, what changes would have occurred during evolution and figure out what, most likely, was the ancestral sequence from which everyone started," he told BBC News.

Rapid break-down

This was purely a computational exercise - it involved no "wet" lab work. The analysis incorporated information from DNA knowledge of the pig, horse, cat, dog, bat, mouse, rabbit, gorilla, chimpanzee, and the human.

MAMMALIAN DNA
Graphic, BBC
The double-stranded DNA molecule is held together by four chemical components called bases
Adenine (A) bonds with thymine (T); cytosine(C) bonds with guanine (G)
Groupings of these letters form the "code of life". In the human genome, there are estimated to be about 2.9 billion base-pairs wound into 24 distinct bundles, or chromosomes
Written in the DNA are 20-25,000 genes, which human cells use as starting templates to make proteins. These sophisticated molecules build and maintain our bodies
All mammalian genomes are very similar - a similar number of bases and genes
The approach is - with current technology - the only way to picture what an ancient genetic make-up might look like. Biological molecules break down very rapidly after an organism dies and researchers would be extremely lucky to find long segments of coherent code surviving in cells beyond a few thousand years.

The study is an extension of ongoing research in what is called "comparative genomics" - the effort to understand the human genome by comparing it with the genomes of other species.

By comparing our code to the ancestral genome, scientists might learn much more than they could from comparisons with other living species, such as the mouse, rat, and chimpanzee, Haussler said.

"If we find a DNA sequence in the human genome that is missing in the corresponding place in the mouse genome, we can't tell whether that DNA was inserted in the evolution of humans from the mammalian ancestor or deleted in the evolution of mice," he said. "If the ancestral genome is available, this ambiguity disappears."

Synthetic life

Of course the "Jurassic Park" question inevitably arises when any researcher talks about recreating ancient genetic code. Would it be possible to synthesise the code of an ancestor and somehow bring it back to life?

The quick and simple answer, scientists say, is "no". The current work has only worked out what a million "letters" of ancestral DNA might look like - and to an accuracy probably of "just" 98%. It is simply not accurate enough.

Eomaia scansoria (AP)
The shrew-like Eomaia scansoria from China is one of the earliest mammal ancestors in the fossil record
Mammalian genomes typically contain three billion bases-pairs of DNA. This means that even if one had sufficient information to reconstruct the entire sequence to 98% accuracy, it would still leave sizeable errors.

"If you gave me your genome and I changed just 1% of the bases, you wouldn't want to do that because just a few changes in important places would not be survivable," said Blanchette.

Nonetheless, the search continues for the fundamentals of life. Scientists have already synthesised a virus from scratch - a copy of the pathogen that causes polio.

Scientists have also identified the smallest number of genes required to sustain life in a bacterial cell (about 350). If they can overcome the many technical hurdles of building a wholly artificial cell in the lab, it is conceivable they could "create" - albeit simple - "life".

But this would be very different from creating organisms on the scale of dinosaurs, or even small shrew-like creatures.





SEE ALSO
Human gene number slashed
20 Oct 04 |  Science/Nature
'Junk' throws up precious secret
12 May 04 |  Science/Nature
Rat's 'life code' read by science
31 Mar 04 |  Science/Nature
First synthetic virus created
11 Jul 02 |  Science/Nature
Fossil sheds light on early mammals
24 Apr 02 |  Science/Nature
Scientists call for life creation debate
10 Dec 99 |  Science/Nature

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