Different Tunes in Different Tissues

In the previous entry, I noted that the alternative splicing of introns facilitates metazoan existence because it allows the organism to produce different versions of the same protein to fit the different versions of cells that make up a body. In other words, a brain cell and muscle cell might express mostly the same genes for their cytoskeleton, but they express different versions of those cytoskeletal genes to facilitate the functions associated with being a neuron vs. a muscle fiber.

Of course, since you might be thinking, “What does that dumb bunny know anyway?,” let me point to a recent study.

First, it was determined that the vast majority of human genes are alternatively spliced:

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.

They also found:

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.
[…..]
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 tissue-dependent. Certain protein isoforms that are common in heart tissue, for example, might be very rare in brain tissue, so that the alternative exon functions like a molecular switch. Scientists who study splicing have a general idea of how tissue-specificity may be achieved, but they have much less understanding of why isoforms display such tissue specificity, Burge said.

From: Human genes sing different tunes in different tissues

So to evolve something as complex as a mammal, the blind watchmaker was given a ready-made strategy for taking the same gene and tweaking it in different tissues as they emerged. Without alternative splicing, there is no reason to think the blind watchmaker could ever have constructed something like a mouse or man.

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2 responses to “Different Tunes in Different Tissues

  1. Mike wrote: “Without alternative splicing, there is no reason to think the blind watchmaker could ever have constructed something like a mouse or man.

    Powerful conclusion.

  2. Unless living organisms are the sum of its coded products, the blind watchmaker doesn’t have a chance.

    For example I think the blind watchmaker can give a human a disease but I don’t think the blind watchmaker can produce a human.

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