Human genes sing different tunes in differe...( CAMBRIDGE Mass. -- Scientists have l...)

CAMBRIDGE, Mass. -- Scientists have long known that it's possible for one gene to produce slightly different forms of the same protein by skipping or including certain sequences from the messenger RNA. Now, an MIT team has shown that this phenomenon, known as alternative splicing, is both far more prevalent and varies more between tissues than was previously believed.

Nearly all human genes, about 94 percent, generate more than one form of their protein products, the team reports in the Nov. 2 online edition of Nature. Scientists' previous estimates ranged from a few percent 10 years ago to 50-plus percent more recently.

"A decade ago, alternative splicing of a gene was considered unusual, exotic but it turns out that's not true at all it's a nearly universal feature of human genes," said Christopher Burge, senior author of the paper and the Whitehead Career Development Associate Professor of Biology and Biological Engineering at MIT.

Burge and his colleagues also found that in most cases the mRNA produced depends on the tissue where the gene is expressed. The work paves the way for future studies into the role of alternative proteins in specific tissues, including cancer cells.

They also found that different people's brains often differ in their expression of alternative spliced mRNA isoforms.

Human genes typically contain several "exons," or DNA sequences that code for amino acids, the building blocks of proteins. A single gene can produce multiple protein sequences, depending on which exons are included in the mRNA transcript, which carries instructions to the cell's protein-building machinery.

Two different forms of the same protein, known as isoforms, can have different, even completely opposite functions. For example, one protein may activate cell death pathways while its close relative promotes cell survival.

The researchers found that the type of isoform produced is often highly ti
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