'Junk' throws up precious secret

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By Julianna Kettlewell

BBC News Online science staff 

 

 

A collection of mystery DNA segments, which seem to be critical for the survival of many animals, are causing great interest among scientists.

Researchers inspecting the genetic code of rats, mice and humans were surprised to find they shared many identical chunks of apparently "junk" DNA.

 

This implies the code is so vital that even 75 million years of evolution in these mammals could not tinker with it.

 

But what the DNA does, and how, is a puzzle, the journal Science reports.

 

Excess baggage?

 

Before scientists began laboriously mapping several animal life-codes, they had a rather narrow opinion about which parts of the genome were important.

 

According to the traditional viewpoint, the really crucial things were genes, which code for proteins - the "building blocks of life". A few other sections that regulate gene function were also considered useful.

 

 

It absolutely knocked me off my chair

David Haussler, University of California 

 

The rest was thought to be excess baggage - or "junk" DNA.

But the new findings suggest this interpretation was somewhat wanting.

 

David Haussler of the University of California, Santa Cruz, US, and his team compared the genome sequences of man, mouse and rat. They found - to their astonishment - that several great stretches of DNA were identical across the three species.

 

To guard against this happening by coincidence, they looked for sequences that were at least 200 base-pairs (the molecules that make up DNA) in length. Statistically, a sequence of this length would almost never appear in all three by chance.

 

Not only did one sequence of this length appear in all three - 480 did.

 

Vital function

 

The regions largely matched up with chicken, dog and fish sequences, too; but are absent from sea squirt and fruit flies.

 

"It absolutely knocked me off my chair," said Professor Haussler. "It's extraordinarily exciting to think that there are these ultra-conserved elements that weren't noticed by the scientific community before."

 

 

DNA: THE CODE OF LIFE

The double-stranded DNA molecule is held together by chemical components called bases

Adenine (A) bonds with thymine (T); cytosine © bonds with guanine (G)

These letters form the "code of life"; there are close to 3 billion base pairs in mammals such as humans and rodents

Written in the DNA of these animals are 25,000-30,000 genes which cells use as templates to start the production of proteins; these sophisticated molecules build and maintain the body 

 

The really interesting thing is that many of these "ultra-conserved" regions do not appear to code for protein. If it was not for the fact that they popped up in so many different species, they might have been dismissed as useless "padding".

But whatever their function is, it is clearly of great importance.

 

We know this because ever since rodents, humans, chickens and fish shared an ancestor - about 400 million years ago - these sequences have resisted change. This strongly suggests that any alteration would have damaged the animals' ability to survive.

 

"These initial findings tell us quite a lot of the genome was doing something important other than coding for proteins," Professor Haussler said.

 

He thinks the most likely scenario is that they control the activity of indispensable genes and embryo development.

 

Nearly a quarter of the sequences overlap with genes and may help slice RNA - the chemical cousin of DNA involved in protein production - into different forms, Professor Haussler believes.

 

The conserved elements that do not actually overlap with genes tend to cluster next to genes that play a role in embryonic development.

 

"The fact that the conserved elements are hanging around the most important development genes, suggests they have some role in regulating the process of development and differentiation," said Professor Haussler.

 

Rethinking "junk" DNA

 

The next step is to pin down a conclusive function for these chunks of genetic material.

 

One method could be to produce genetically engineered mice that have bits of the sequences "knocked out". By comparing their development with that of normal mice, scientists might be able to work out the DNA's purpose.

 

Despite all the questions that this research has raised, one thing is clear: scientists need to review their ideas about junk DNA.

 

Professor Chris Ponting, from the UK Medical Research Council's Functional Genetics Unit, told BBC News Online: "Amazingly, there were calls from some sections to only map the bits of genome that coded for protein - mapping the rest was thought to be a waste of time.

 

"It is very lucky that entire genomes were mapped, as this work is showing."

 

He added: "I think other bits of 'junk' DNA will turn out not to be junk. I think this is the tip of the iceberg, and that there will be many more similar findings."

 

Story from BBC NEWS:

http://news.bbc.co.uk/go/pr/fr/-/1/hi/sci/tech/3703935.stm

 

Published: 2004/05/12 13:56:24 GMT

 

© BBC MMV

 

Rat's 'life code' read by science

By Jonathan Amos

BBC News Online science staff 

 

 

Scientists have decoded the rat genome, the biochemical instructions in the rodent's cells that guide the building and maintenance of the animal's body.

It is the third mammalian DNA sequence to be deciphered - humans and mice came first - and will be used by researchers to understand the causes of disease.

 

It should also give valuable insights into the evolution of all mammals.

 

The work by an international team led by the US Baylor College of Medicine is reported in the journal Nature.

 

 

Better rat models will decrease drug failure in clinical trials

Prof Howard Jacob 

 

The rat was made a priority species to decode because of its importance to medical research.

For nearly 200 years, scientists have used the animal as a "model" on which to test ideas about human biology.

 

Today, the rat, along with its rodent cousin the mouse, account for more than 80% of all laboratory experiments. Scientists have hundreds of strains of mice and rats that mimic human illnesses.

 

Quicker development

 

Now, researchers say the information contained in the rat genome will help produce disease models that are an even closer match for the sick conditions found in humans.

 

"Rats remain the dominant pre-clinical model of human disease for developing new drugs," said Professor Howard Jacob, from the Medical College of Wisconsin, US, and a senior author on the Nature paper.

 

 

RAT DNA - RATTUS NORVEGICUS

The double-stranded DNA molecule is held together by chemical components called bases

Adenine (A) bonds with thymine (T); cytosine© bonds with guanine (G)

These letters form the "code of life"; there are estimated to be about 2.75 billion base pairs in the rat genome wound into 22 distinct bundles, or chromosomes

Written in the DNA are possibly 25,000 genes which rat cells use as templates to make proteins; these sophisticated molecules build and maintain the animal's body 

 

"Better rat models will decrease drug failure in clinical trials - currently standing at about 90% - which will decrease development costs and time to market."

The Rat Genome Sequencing Project Consortium used a strain of a brown Norway rat ( Rattus norvegicus ) to obtain the genetic information. Two females and a male provided the biological samples for the study.

 

More than 90% of the rat's DNA has been read, sorted and analysed in what the consortium describes as a "draft". The remaining less than 10% is not thought to contain significant data and no current plans are in place to try to retrieve this information.

 

The research found the rat genome to be of a similar size to humans and mice - at 2.75 billion "letters", or bases, of DNA. It also contains a comparable number of genes - about 25,000.

 

And it is clear that most of the genes found in the rat can be seen in the human code, too.

 

Of rodents and dogs

 

"If one looks at genes that are basically equivalent, then nine out of 10 are the same," said Professor Chris Ponting, from the UK Medical Research Council's Functional Genetics Unit, who worked on the project.

 

"The disease genes are nearly all within that 90% - they're conserved between rodents and humans. Therefore, in looking at the biology of human disease genes in rodents, it appears rodents make excellent models," he told BBC News Online.

 

 

HOW SOME LAB RATS ARE USED

To practise surgery; to study cancer, diabetes, and cardiovascular disease; to investigate psychiatric disorders, neural regeneration, and space motion sickness

In drug development, the rat is employed to demonstrate therapeutic efficacy and assess toxicity of novel drug compounds before human clinical trials 

 

Some families of genes, though, have been greatly expanded in the rat, including, perhaps not surprisingly, those associated with the ability to emit and sense smells.

There are significant distinctions, also, in the genes of the immune system.

 

Comparison of the rat code with those of the human and the mouse should allow a remarkable view of mammalian evolution.

 

The rat data shows about 40% of the modern mammalian genome derives from the last common mammalian ancestor that existed tens of millions of years ago. This "core" DNA encodes nearly all the genes and their regulatory signals, and accounts for the similarities among mammals, such as the basic body plan.

 

More details about the fundamental biochemistry and evolution of mammals will become apparent when scientists get to compare the human and the rodent codes with those of the soon-to-be finished chimp and dog genomes.

 

"What we know about the dog is that genetically speaking it is closer to humans than rodents, even though in terms of evolution it is further away," explained Professor Ponting.

 

"That's to say, the dog lineage split off from the human lineage before rodents - it's just that the rodents' DNA has mutated like crazy since then."

 

 

Story from BBC NEWS:

http://news.bbc.co.uk/go/pr/fr/-/1/hi/sci/tech/3586573.stm

 

Published: 2004/03/31 23:30:09 GMT

 

© BBC MMV