Thursday, June 14, 2007

Junk DNA is Not Really Junk

My undergraduate degree was in Chemistry, but I had a serious load of biology as well, and my thesis project was in biochemistry. I still have a strong interest in biology, and forgive me if I use this space to discuss a fairly momentous development in genetics. For years scientists have known that only a very small fraction of DNA is used to create proteins, and the remaining DNA has generally been viewed as "junk DNA" that had little or no apparent use.

Well, as the Washington Post reports, this view is very wrong. Junk DNA appears to play a very important role that we are just beginning to unerstand:

The findings, from a project involving hundreds of scientists in 11 countries and detailed in 29 papers being published today, confirm growing suspicions that the stretches of "junk DNA" flanking hardworking genes are not junk at all. But the study goes further, indicating for the first time that the vast majority of the 3 billion "letters" of the human genetic code are busily toiling at an array of previously invisible tasks.

The new work also overturns the conventional notion that genes are discrete packets of information arranged like beads on a thread of DNA. Instead, many genes overlap one another and share stretches of molecular code. As with phone lines that carry many voices at once, that arrangement has prompted the evolution of complex switching, splicing and silencing mechanisms -- mostly located between genes -- to sort out the interwoven messages.

. . .

The findings come from the Encyclopedia of DNA Elements project, nicknamed Encode. While much of the decades-long effort to understand DNA's role in health and disease has been driven by scientists' interest in particular genes, Encode focused on a representative 1 percent of the genome. Using a variety of experimental and computational approaches, the researchers sought to catalogue everything going on there.

The 3 1/2 -year effort was designed as a pilot project to see whether it would be practical to study the entire genome in such depth and to hasten the development of cheaper tools to do so. Encode was so successful, Collins said, that the remaining 99 percent of the genome is expected to be studied the same way for $100 million.

Researchers have long known that only about 2 percent of human DNA is involved in making proteins, the molecular workhorses inside cells. That involves a two-step process in which a stretch of DNA -- a gene -- serves as a template to produce a strand of RNA, which is then used as a template to produce a protein.

Recent studies had shown that some snippets of DNA between genes also are transcribed into RNA even though they do not go on to make proteins. Surprisingly, though, the new work shows that most of a cell's DNA gets transcribed, raising questions about what all that RNA is doing.

Some of it may be doing nothing. "It may be like clutter in the attic," Collins said, noting that clutter could be useful when conditions change and evolution needs new material to work with.

But much of it seems to be playing crucial roles: regulating genes, keeping chromosomes properly packaged or helping to control the spectacularly complicated process of cell division, which is key to life and also is at the root of cancer.

Read it all.

The New Scientist elaborates that the old dogma that only a small percentage of DNA is used to replicate proteins is not wrong. Instead, the "junk DNA" appears to be important in RNA operations that are only beginning to be understood:
It turns out that DNA generates far more RNA than the standard dogma predicts it should - even some "junk" DNA gets transcribed. The Encyclopedia of DNA Elements (ENCODE) project has quantified RNA transcription patterns and found that while the "standard" RNA copy of a gene gets translated into a protein as expected, for each copy of a gene cells also make RNA copies of many other sections of DNA. None of the extra RNA fragments gets translated into proteins, so the race is on to discover just what their function is.

"One of the critical questions is whether they're important or not, and we simply don't know," says Ewan Birney, head of genome annotation at the European Bioinformatics Institute in Cambridge, UK, and analysis coordinator for the ENCODE project, which involves many labs from around the world.

Birney says that while the central dogma still holds, the discovery of so much extra RNA could mean there are hitherto unrecognised subtleties of gene regulation that now need to be explained. "It's no longer the neat and tidy genome we thought we had," says John Greally of the Albert Einstein College of Medicine in New York City
. . .

Birney says that the additional switches may be mutations that appear by accident and then generate new slugs of RNA, but because they are produced randomly, most are evolutionarily neutral "passengers" in the genome. There might be rare occasions, however, when a new RNA does confer an advantage.

Tom Gingeras of genomics firm Affymetrix in Santa Clara, California, and a co-leader of ENCODE, disagrees. He first reported transcription of non-coding DNA three years ago (New Scientist, 21 February 2004, p 10), and is convinced that the extra RNAs have a function, perhaps to help transport molecules around the cell or fine-tune and modulate the activity of genes themselves. "We don't think they're produced by accident," he says

Read it all.

There are several interesting implications of this work. It suggests that DNA works in more complicated ways than originally thought, and this breakthrough may begin to answer questions about why the same DNA in a skin cell and a brain cell operates to create such different cells. It may also begin the explain some of the complicated issues of nature versus nurture.

What are the religious implications? Heck, I don't know, but this is very important science and all of you should know about it.

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