Cells compute ratios to control gene expression

Randomness has no role in biodiversity


Excerpt: "In multicellular animals, cells communicate by emitting and receiving proteins, a process called signaling. One of the most common signaling pathways is the transforming growth factor b (Tgf-b) pathway, which functions in all animal species throughout their lifetimes and regulates numerous biological processes, such as instructing cells how to differentiate—whether a stem cell will become a muscle cell or a bone cell, for example.

But how do cells decipher those signals and use that information to guide gene expression? The answer, according to new research from the laboratory of Lea Goentoro, assistant professor of biology at Caltech: the cells perform simple division. In other words, they do math.
The cell's detection of the Tgf-b signal triggers a series of molecular interactions, culminating in changes in the abundance of a protein called Smad3. A kind of messenger, Smad3 is activated at the cell membrane when a cell encounters the Tgf-β signal, and ultimately ends up in the nucleus of the cell where it directs gene expression. Biologists have commonly believed that the degree to which gene expression is changed will depend on how much Smad protein is produced after exposure to Tgf-β.

In order to study how Smad responds to Tgf-b in real time, the researchers made movies of the signaling process in individual cells. They discovered that the pathway did not behave as biologists had previously thought. After exposure to the Tgf-b signal, the researchers found, Smad3 did indeed move to the nucleus, as expected. The surprise was that the abundance of Smad3 was significantly different in each cell. And yet, despite those wildly varying concentrations of Smad3, the level of Smad3 after the signal divided by the level before the signal was consistent in each cell.

This observation led the researchers to hypothesize that cells are somehow able to compute this ratio and that the gene response is proportional to this relative change (called a fold-change) rather than to the abundance of Smad3.

"This result is nonintuitive: it is easy to imagine how a cell can increase the expression of a target gene by increasing the abundance of Smad3," says Frick. "Thus, many of us had expected that the abundance of Smad3 would be tuned in response to the Tgf-β signal. In contrast, what these cells regulate is the ratio of the change in abundance of Smad3. The big question now is: How does a cell compute this ratio and then adjust gene expression accordingly?"

My comment: Cellular mechanisms are extremely complex. Signaling pathways, readers, writers and erasers point to design. Several forms of information (Digital, analog and meta-data) in the cell tell us about living machines that are much more complex than human designed computers. Randomness has no role in biodiversity.