A new study from North Carolina State University shows that genes are able to identify and respond to encoded information in light signals, as well as completely filter out some signals. Research shows how the same mechanism can cause different behaviors of the same gene, and can find applications in the biotechnology sector.
"The fundamental idea is that it is possible to encode information in the dynamics of the signal that the gene receives"says Albert Keung, co-author of the article and assistant professor of chemical and biomolecular engineering at NC State." So, instead of just being present or not, what matters is how it is presented."
For this study scientists modified a yeast cell to contain a gene that produces fluorescent proteins when the cell is exposed to blue light.
This is how it works. A region of a gene called a promoter is responsible for controlling gene activity. In modified yeast cells, a specific protein binds to the promoter region of the gene. When researchers illuminate this protein with blue light, it becomes susceptible to a second protein. When the second protein binds to the first, the gene becomes active. And this is easy to spot because the activated gene produces proteins that glow in the dark.
Then researchers exposed these yeast cells to 119 different light patterns … Each light pattern differed in light intensity, duration of each light pulse, and pulse frequency. The researchers then quantified the amount of fluorescent protein the cells produced in response to each light pattern.
The data obtained indicate that genes turn on or offbut it's less like a light switch and more like a toggle switch - gene can be activated a little, a lot, or somewhere in between. If a given light pattern resulted in the production of a large amount of fluorescent protein, it means that this light pattern made the gene very active. If the light pattern produced a small amount of fluorescent protein, it meant that the pattern caused only weak gene activity.
“We found that different light patterns can produce very different results in terms of gene activity,” says Jessica Lee, first author of the paper and a recent NC State PhD graduate. “The big surprise for us was that the output was not directly related to the input. We expected that the stronger the signal, the more active the gene would be. But this was not necessarily the case. One light pattern could make a gene significantly more active than another. even if both patterns exposed the gene to the same amount of light."
The researchers found that all three light pattern variables - light intensity, light pulse frequency, and the duration of each pulse - could influence gene activity, but they found that Controlling the frequency of light pulses gives them the most accurate control over gene activity.
“We also used our experimental data to develop a computational model that helped us better understand why different circuits cause different levels of gene activity,” says Leandra Caywood, a co-author of the paper and a graduate student at NC State.
"For example, we found that when fast pulses of light are very close to each other, we get higher gene activity than would be expected from the amount of light supplied," says Keywood. “Using the model, we were able to determine that this is because proteins cannot dissociate and clump together quickly enough to respond to each impulse. In fact, proteins do not have time to completely separate from each other between impulses, so they spend more time in connection - this means that the gene spends more time in an activated state. Understanding these kinds of dynamics is very useful in helping us understand how to better control gene activity through these signals."
“Our finding is relevant for light-responsive cells such as those in leaves,” Keung says. "But it also tells us that genes respond to signals that can be delivered not only by light, but also by other mechanisms".
A comment: if the DNA is some kind of antenna, perhaps the vast majority of cells can be made to respond to certain signals
Consider that managing the presence and absence of this protein is the transmission of a Morse code message from cell to gene. Depending on many other variables - such as the presence of other chemicals - the cell can fine-tune the message it sends to the gene to modulate its activity.
"This tells us that the same protein can be used to transmit different messages to the same geneKeung says, "So a cell can use one protein to make a gene respond differently to different chemicals."
In a separate series of experiments, the researchers found that genes are also capable of filtering out certain signals. The mechanics of this phenomenon are both simple and mysterious … The researchers were able to determine that when a second protein binds to the promoter region of a gene, certain frequencies of the light pulses do not trigger the production of fluorescent proteins. In short, the researchers know that the second protein ensures that the gene only responds to a specific set of signals - but the researchers don't know exactly how the second protein does this.
The researchers also found that they can control the number of different signals a gene can respond toby manipulating the number and type of proteins attached to the promoter region of the gene.
For example, proteins can be attached to the promoter region that serve as filters that limit the number of signals that activate a gene. Or, proteins can be attached to the promoter region that cause varying degrees of gene activation.
"An additional contribution of this work is that we have determined that we can transfer about 1.71 bits of information through the promoter region of the gene with just one protein", says Lee. In practical terms, this means that the gene, without a complex network of protein attachments, is able to accurately distinguish more than 3 signals". In previous work, this baseline has been set at 1.55 bits, so this study expands our understanding of what is possible here. This is the foundation on which we can build."
The researchers say this work allows for future research that will advance our understanding of the dynamics of cell behavior and gene expression.
In the short term, according to the researchers, the work may find practical application in pharmaceutical and biotechnological sectors.
"In bioproduction, you often need to control both the growth of cells and the rate at which those cells make certain proteins," says Lee."Our work can help manufacturers fine tune and control both of these variables."
This work was supported by the National Science Foundation under Grant 1830910 "New Frontiers in Research and Innovation" and the National Institutes of Health under Grant 5T32GM133366.