94 percent of human genes generate multiple forms of their protein products

Almost all human genes, about 94 percent, generate more than one form of their protein products by skipping or including certain sequences from the messenger RNA, say MIT scientists.

The phenomenon, called alternative splicing, is much more prevalent and varies more between tissues than was previously believed.

Ten years ago, the scientists thought that the phenomenon was limited to only a few genes, but the figure reached 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," Nature magazine quoted Christopher Burge, senior author of the paper and the Whitehead Career Development Associate Professor of Biology and Biological Engineering at MIT, as saying.

The researchers discovered that in majority of the cases, mRNA produced depends on the tissue where the gene is expressed.

The study opens the door for future studies into the role of alternative proteins in specific tissues, including cancer cells.

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

Isoforms, i.e. two different forms of the same protein, can have different, even completely opposite functions.

For example, one protein may activate cell death pathways while its close relative promotes cell survival.

They revealed that the type of isoform produced is often highly tissue-dependent, and also that the cells express different isoforms during embryonic development and at different stages of cellular differentiation.

Now, the researchers are studying cells at various stages of differentiation in order to find out when different isoforms are expressed.

Isoform switching also occurs in cancer cells, the knowledge of which, could lead to potential cancer therapies, said Burge.

Till date, it was quite difficult to study isoforms on a genome-wide scale, owing to the high cost of sequencing and technical issues in discriminating similar mRNA isoforms using microarrays.

In the study, researchers took mRNA samples from 10 types of tissue and five cell lines from a total of 20 individuals, and generated more than 13 billion base pairs of sequence, the equivalent of more than four entire human genomes.

The study is published in the latest online edition of Nature. (ANI)

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