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How Science Is Rewriting the Book on Genes

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By David Brown
Washington Post Staff Writer
Monday, November 12, 2007

Everyone who goes to medical school hears this story at some point.

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Graduation day comes and the new doctors assemble to get their diplomas. The dean gazes out and announces sheepishly: "I'm sorry to tell you that half of what we taught you is wrong. The problem is, we don't know which half."

Nowhere has this been more evident than in genetics.

The rules of inheritance, and hints of the biological mechanisms behind them, were first elucidated by Gregor Mendel in the 1860s. Over the ensuing 130 years, scientists gained insight at a molecular level into how biological information is recorded, preserved, used and passed on to future generations.

In recent years, however, many of the certainties gained over that long run are being overturned.

Ever better tools for cutting and splicing strands of DNA, combined with the explosion of data from sequencing the genomes -- the inherited genetic instruction books -- of humans and more than a dozen other organisms, are the engines driving this revolution.

Here are some of the recent revisions of what were once canonical rules of genetics.

What Is a Gene?

DNA, or deoxyribonucleic acid, is a molecule made of four chemical compounds, called nucleotides, strung end to end like beads on a string. The nucleotides are designated by the letters A, T, C and G. In fact, they function like letters, carrying instructions that are spelled out in three-letter "words" -- ATG, CAC, etc. -- never two letters or four letters or five letters. The human genome consists of 3.1 billion nucleotide pairs, strung together in a particular order.

Classically, a gene is a stretch of DNA within a cell that contains the instructions for making a protein. A gene has a section of DNA that marks its starting point, a body consisting of coding sequences (called exons) interspersed with filler areas (called introns), and a termination point. The three-letter words in the coding sequences specify the order of the different amino acids that will make up a protein: the gene's product.

When a gene is activated, it is first transcribed into an intermediate molecule called mRNA. The introns are clipped out and the exons spliced together, and the whole thing is then translated into the protein.

Biologists used to think one gene produced one protein. Now it's clear that one gene can produce many different proteins. Under certain conditions, a cell clips out not only the intron fillers but also one or more of the exons. This is like taking a speech and removing many of the sentences. Done in different ways, it can produce many different messages.

"Alternative splicing represents the most significant driving force to diversify the output of a finite genome," says Hal Dietz, a Johns Hopkins University physician and genetics researcher.


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