Evolution of the Immunoglobulin Isotypes-Variations of Biophysical Properties among Animal Classes

The adaptive immune system arose around 500 million years ago in jawed fish, and, since then, it has mediated the immune defense against pathogens in all vertebrates. Antibodies play a central role in the immune reaction, recognizing and attacking external invaders. During the evolutionary process, several immunoglobulin isotypes emerged, each having a characteristic structural organization and dedicated function. In this work, we investigate the evolution of the immunoglobulin isotypes, in order to highlight the relevant features that were preserved over time and the parts that, instead, mutated. The residues that are coupled in the evolution process are often involved in intra- or interdomain interactions, meaning that they are fundamental to maintaining the immunoglobulin fold and to ensuring interactions with other domains. The explosive growth of available sequences allows us to point out the evolutionary conserved residues and compare the biophysical properties among different animal classes and isotypes. Our study offers a general overview of the evolution of immunoglobulin isotypes and advances the knowledge of their characteristic biophysical properties, as a first step in guiding protein design from evolution.

Automated summary

This study investigates the evolution of immunoglobulin isotypes, highlighting the preserved features and the parts that have mutated over time. Coupled residues in the evolution process are crucial for maintaining the immunoglobulin fold and interactions with other domains. By comparing biophysical properties across different animal classes and isotypes, conserved residues in evolution can be identified. This study offers a general overview of the evolution of immunoglobulin isotypes and advances the understanding of their characteristic biophysical properties for guiding protein design.