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Palaeogenomics: The ancestor of all mammals

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Divine Wind
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PostPosted: 01-12-2004 16:31    Post subject: Palaeogenomics: The ancestor of all mammals Reply with quote

We seem to be getting there genetically (does this mean we can clone them?):

Ancestor's DNA code reconstructed

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 code - 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.


The double-stranded DNA molecule is held together by chemical components called bases
Adenine (A) bonds with thymine (T); cytosine(C) bonds with guanine (G)
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 ancient DNA code 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.

Mammalian genomes typically contain three billion bases 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.

Story from BBC NEWS:

Published: 2004/12/01 00:54:32 GMT


Scientists reconstruct ancestral genetic code

Computer analysis blends paleontology and genomics in search for mammalian ancestor

David Haussler, a Howard Hughes Medical Institute investigator at the University of California at Santa Cruz, uses computer software to analyze similarities and differences in the genetic codes for humans and other mammals.

By Alan Boyle
Science editor
Updated: 8:06 p.m. ET Nov. 30, 2004

Researchers have reconstructed a long string of genetic code for what they believe is the common ancestor of placental mammals — a shrewlike creature that lived in Asia more than 75 million years ago.

The leader of the research team, David Haussler of the University of California at Santa Cruz, admits that the concept may sound like the plot line for a "Jurassic Park" sequel. But he says the real point of the research is to learn how the evolutionary paths of different species diverged over time — and make it easier to decipher present-day genetic code.

"It's driven by curiosity about our own origins," Haussler told Tuesday. "If we really want to understand in detail, at the molecular level, how evolution works, we have to reconstruct the evolutionary history of every base in the genome. It's only then that we'll see the key events."

Exercise in paleogenomics

The supposed ancestor is long gone, of course, and scientists don't plan to bring it back to life. Rather, this experiment served as an exercise in "paleogenomics" — the application of genetics to scientific questions about the ancient past.

To come up with the ancestral genetic code, scientists looked at a closely studied 10-gene region of the mammalian genome known as the CFTR locus. That region has been linked to the incidence of cystic fibrosis, so medical researchers have spent a lot of time compiling the code not only for humans, but for many other animals as well.

The code string consists of more than 1 million base pairs, or "letters" that read like this: GTCACAATT. A sophisticated computer program compared the equivalent strings for humans and 18 other placental mammals — that is, mammals who carry their young to birth within a placenta, as opposed to a pouch.

Each of the 19 species exhibited its own additions, subtractions and changes in the genetic code. The computer looked beyond those differences to develop a consensus version of the code, using a mathematical formula weighted to account for evolutionary theory.

The scientists concluded that their results reflected the code for the common ancestor to an accuracy of 98 percent, based on repeated simulations and comparisons with the genetic codes for animals outside the original group, such as chickens and opossums.

Expedition into DNA

Just looking at the reconstructed code, you couldn't tell whether this common ancestor was a mouse or an armadillo. However, previous research has pointed to a shrew-sized animal known as Eomaia scansoria as one of the earliest placental mammals. Haussler said the genetic code generated by his team probably described a similar but more recent creature that existed more than 75 million years ago, when dinosaurs walked the earth.

"It's like a paleontological expedition, but into the DNA, not literally into the rocks," he said.

Haussler said his team is confident about the accuracy of the results in part because the mammalian branches spread out so quickly from the roots of the evolutionary family tree.

"You had a very rapid radiation of different lineages ... that fanned out like a starburst," he explained. "It's like there was an ancient text, and 20 different copies of this text were stored away in different places, and each one underwent independent and separate types of decay processes. You have a better chance of reconstructing the actual ancient text if the different changes on the different copies were independent."

Ironically, the technique doesn't work nearly as well to find the common ancestral code for cats and dogs, which are relatively close on the evolutionary tree.

Haussler, a Howard Hughes Medical Institute investigator, was joined in the research by Mathieu Blanchette of McGill University. Eric Green of the National Human Genome Research Institute and Webb Miller of Penn State University. Their findings were published in the December issue of the journal Genome Research.

Our genetic ancestors?

Cornell University geneticist Rasmus Nielsen said the newly published study would likely spark more work in the field. "Previously it was thought that we would never really know what our ancestors looked like at the genetic level, but now it appears that we'll be able to tell," he said.

Haussler said much more genetic data would be required to focus in on the full ancestral genome. Although the 1.1 million base pairs of the CFTR locus sound like a huge number, the full genome amounts to a whopping 3 billion base pairs.

Nevertheless, Haussler believes the technique he and his colleagues used could someday produce new insights into evolutionary history. "It's possible that some of these evolutionary changes will be studied in the laboratory to see the effect of a gene," he said.

For example, he suggested that particularly intriguing portions of ancestral DNA could be synthesized and inserted into mouse genes for testing. Such experiments could in turn yield new medical advances.

"We haven't even scratched the surface in terms of understanding the changes that actually occurred on a molecular level during our evolution," he said. "It's a completely wide-open field at this point, and I think there's much to discover."

© 2004 MSNBC Interactive

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Divine Wind
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PostPosted: 01-12-2004 16:34    Post subject: Reply with quote

Shorter story on the general principles:

Scientists plan Jurassic archive

By Palab Ghosh
BBC science correspondent

Researchers in the US say a new computer programme could reconstruct parts of the genetic make-up of animals extinct for millions of years.

In the journal Genome Research scientists say the programme could teach us how such animals evolved.

It is early days, but the system could in principle be used to create a computerised zoo.

It could perhaps hold the complete DNA of all the animal and plant life that ever existed on Earth.

This would be a remarkable feat.

Key moments

But the obvious question is: could the scientists do something even more remarkable, and bring any of these long-lost creatures back to life using cloning techniques, as happened in the film Jurassic Park?

Probably not, the scientists say - at least, not yet.

It is currently too expensive and time-consuming to recreate the DNA of all but the most simple forms of life - but who knows what might happen in the future?

In the meantime, the development is creating huge excitement among those who study evolution.

It could enable biologists to track important moments in the development of various species.

It could also give them more details of what ancient creatures were really like.

One key area of research will be to identify the genetic changes that made modern humans more intelligent than other animals.

Story from BBC NEWS:

Published: 2004/12/01 02:36:02 GMT

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Vogon Poet
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PostPosted: 08-02-2013 02:22    Post subject: Reply with quote

Meet Your Mama: First Ancestor of All Placental Mammals Revealed

A tiny, furry-tailed creature is the most complete picture yet as to what the ancestor of mice, elephants, lions, tigers, bears, whales, bats and humans once looked like, researchers say.

These new findings also suggest this forerunner of most mammals appeared shortly after the catastrophe that ended the age of dinosaurs, scientists added.

"Species like rodents and primates did not share the Earth with nonavian dinosaurs, but arose from a common ancestor — a small, insect-eating, scampering animal — shortly after the dinosaurs' demise," said researcher Maureen O'Leary at Stony Brook University in New York.
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