Directed evolution is a method that allows researchers to create several varieties of proteins starting from an initial template. It is inspired by the process of natural selection that shapes the evolution of organisms.

An example of directed evolution with comparison to natural evolution. The inner cycle indicates the 3 stages of the directed evolution cycle with the natural process being mimicked in brackets. The outer circle demonstrates steps a typical experiment. The red symbols indicate functional variants, the pale symbols indicate variants with reduced function. Credit: Thomas Shafee, via Wikimedia Commons
Directed evolution explained

Basically, an initial element (for example a protein) is gradually altered through mutations until its properties change according to the desire of the experimenter. For example, one could develop an enzyme that is ten times more efficient than the starting template enzyme.

In brief, the process starts with defining the scope of the evolution: what type of protein, enzyme, etc. is desired, what are its properties and what is the existing protein that will serve as the starting point (template).

Next, the gene that codes for the template protein is isolated. Subsequently, this gene is subjected to repetitive cycles of mutagenesis (mutations are induced), creating a collection (library) of genetic variants.

Next, the variants are tested for specific, desired characteristics. This is the selection step, which allows for the identification of promising variants.

The variants selected in the previous stage are then amplified to generate a new template for a new round of mutations. The process is repeated until a protein with the desired characteristic, defined at the beginning of the process, is obtained.

Directed mutagenesis can be performed both in vitro and in vivo. Many techniques and approaches are available. The method is used for protein engineering, but also to study the principles of evolution in a controlled environment.