Deciphering the Evolutionary Path of Regulatory Proteins: New Research from the University of Wisconsin-Madison

2024-03-30 05:23:23

New research from the University of Wisconsin-Madison deciphers the evolutionary path of regulatory proteins, the molecules that help control gene expression.

The findings from the Raman Laboratory in the Department of Biochemistry recently published their findings in the journal cell systems. Here’s a summary of what they discovered:

• Proteins acquire and lose functions through evolutionary processes as cells adapt to changes in their environment over time.
• Protein development is well studied in certain enzymes, but it is not studied in regulatory proteins, which help control gene expression.
• A comprehensive new study of the evolution of a single regulatory protein reveals that the way proteins evolve to gain and lose functions over time differs between protein classes. While some proteins evolve in a stepwise fashion, slowly gaining or losing functions over time, proteins that are charged with controlling important functions such as gene expression follow an evolutionary pattern that protects them from performing multiple functions at the same time.

What background information do you need to know?

The finches of the Galapagos, described by Darwin, are often used as the quintessential example of evolution. Over time, naturally occurring genetic mutations have led to small, cumulative changes in the birds’ appearance. Changes that gave finches an advantage were passed on to the next generations, and eventually resulted in a variety of beak shapes and body shapes that are well adapted to different diets and techniques.

Biomolecules also evolve over time to acquire new functions and lose redundant ones in response to changes in the cell’s environment, such as exposure to new molecules or the introduction of pathogens. This evolution is a continuous process that favors mutations that allow organisms to function effectively and efficiently.

For example, scientists know that enzymes -; A class of proteins that are responsible for initiating and accelerating biochemical reactions -; develop gradually. Individual mutations accumulate, eventually giving the enzyme a new function in the cell.

But this pattern of evolution is not true for all types of proteins.

Why do the evolutionary patterns differ between proteins?

While some proteins can gradually evolve to change their functions, sometimes even performing multiple functions in stages along the way, regulatory proteins have a more delicate balance system.

Regulatory proteins help control gene expression, turning genes on and off like a light switch. If a single light switch controls the expression of multiple genes, it becomes more difficult to control the expression of just one of the genes. This is why regulatory proteins usually have a limited set of functions: performing multiple related functions can lead to catastrophic effects, including cell death, altered gene expression, or uncontrolled cell division, which can cause tumors. The stakes of mutation and development are higher when protein function is so important and complex.

How did scientists progress?

To better understand the evolutionary trajectory of regulatory proteins, Vatsan Raman and researchers in his lab mapped the evolution over thousands of years of a particular type of regulatory protein called a transcription regulator. This protein helps control the rate at which RNA is synthesized from DNA.

They deduced a probable history of the protein’s mutations using computer models. This approach gave them hundreds more DNA sequences representing the evolutionary history of the protein than in previous studies. Using this data, they followed the probable mutations of the protein -; and the resulting gain and loss of function -; Revealing an innovative evolutionary pattern.

In contrast to the stepwise patterns seen in enzymes, transcriptional regulatory proteins rapidly gain or lose function when they acquire mutations. This rapid change helps them maintain their unique role of binding to specific molecules, preventing them from performing multiple roles at the same time.

Raman and his team believe that the evolutionary pattern revealed by their research in transcriptional regulation may also appear in other regulatory proteins. A deeper understanding of the evolutionary landscape of transcription regulators will help scientists design new regulators to control gene circuits, sense molecules, engineer biosynthetic pathways and monitor cellular metabolites, opening the door to new biomedical and biotechnological discoveries.