An Updated View on the “Central Dogma” of Molecular Biology

Recently, a research team from the University of California San Diego has shown that changes in gene expression for the model bacterium E. coli happen almost entirely during the transcription stage while the cells are growing. The researchers provided a simple quantitative formula linking regulatory control to mRNA and protein levels in their current work. The journal Science published the novel findings on December 9, 2022.

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The Linear Principle at the Molecular Level

The direction of the information flow from DNA to mRNA to protein is called the “central dogma” of molecular biology, as coined by Nobel laureate Francis Crick. This principle is straightforward on an individual-gene level: turn on a gene, copy mRNA, and create proteins from the mRNA. 

The general belief of gene regulation works in such a linear fashion as scientists design experiments that change only a single gene or a few genes specific to their studies without drastically affecting the entire cell system. According to this theory, making twice as many mRNAs would double the production of proteins. However, the linear way of thinking about the central dogma may not be true when considered at a systems level.

This is because cells must deal with certain global constraints. For instance, the total protein concentration in a cell is approximately constant. When the environment changes and cells adapt by regulating the expression of certain genes, these global constraints force additional changes in the expression of these genes and others that are not directly regulated.  

New Framework to Create Efficient Genetic Circuits

The team targeted the consideration of global constraints and focused on the problem from the opposite end. They started with the constraints and then made quantitative statements with absolute measurements beyond the relative measurements commonly used. The advantage of absolute quantitative measurements is to allow researchers to quantitatively relate mRNA levels to protein levels and vice versa.

The researchers believed that it would help In the synthetic biology context, as scientists often see circuits they spent much effort developing in one environment fail in another. Using the updated framework, scientists could create genetic circuits fitting multiple environments with a simple recipe.

As a result, the precise manipulation of protein levels provides new insights to investigate host immunity, re-engineering bacteria for uses such as detecting and cleaning up toxic waste or being sent into the body to kill cancer cells. More importantly, this could solve problems in medicine, manufacturing, and agriculture through the redesign and re-engineering of genes and their interactions. 

Author

Nai Ye Yeat