Reconstructed ancient protein maps how bacterial enzymes evolved distinct functions

This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: How do related proteins develop different functions? This is the question investigated by a research team involving Kiel University, DESY and the Center for Structural Systems Biology (CSSB).

Led by Holger Sondermann, professor at Kiel University and head of the Structural Microbiology group at DESY, the researchers reconstructed the common ancestor of two bacterial enzymes and produced the long-extinct protein in the laboratory. Their findings, published in Science Advances, provide insights into how proteins can evolve different functions over the course of evolution. The two enzymes studied belong to a group of proteins known as nucleases.

These proteins break down certain molecules made up of the building blocks of genetic material. NrnC is an enzyme that breaks down small molecules consisting of two linked DNA or RNA building blocks. The enzyme diDNase performs a similar function but is mainly specialized in processing molecules made up of two DNA building blocks.

The researchers wanted to understand how these distinct functions evolved. The new study builds on several years of research by the Sondermann group. The researchers compared proteins from different bacteria to determine which characteristics have remained conserved over time and which have changed.

In earlier studies of a particular enzyme family, Sofia Mortensen, a scientist in the Sondermann group, identified a group of proteins that were closely related to known enzymes but processed different molecules. The team initially tried to explain the differences between the two enzymes by introducing targeted changes into the proteins. However, the modified proteins either lost their stability or failed to perform the expected function.

The researchers therefore had to take a different approach. Rather than simply comparing the proteins that exist today, they looked back at their evolutionary history. To do this, they used a method known as ancestral sequence reconstruction.