The Advanced Light Source (ALS) characterized a protein from a modern shark gene that explains the evolution of the adaptive immune system shared by all vertebrates.
Understanding the emergence of the adaptive immune system may aid researchers in advancing immunology, genetics, and biotechnology.
Left: The crystallographic model of the N-terminus of the UrIg2 protein from a nurse shark. Right: An example of one modern human antibody (IgG) whose variable region gene undergoes rearrangement.
The rise of adaptive immunity
Humans defend against infections through both the innate and adaptive immune systems. The innate response provides the first line of rapid defense, but it lacks both a way to address specific pathogens and a memory response to launch against attack by a returning invader. The adaptive immune system acts as a second line of defense. It lags behind the innate system because it must construct the antibodies to fight specific pathogens. The strength of this dual approach lies in the memory retained in the cells that produce antibodies that can be recalled to neutralize a returning threat.
The adaptive immune system is shared by all vertebrates and is believed to have developed soon after a genome-wide duplication event that occurred approximately 500 million years ago. The scientific community theorizes that the adaptive immune system developed when a mobile genetic element from a microbe—a recombination-activating gene (RAG) transposon—inserted itself into and split a gene in a eukaryotic cell, likely a white blood cell.
This random event led to a monumental and life-altering outcome. The process brought the repetitive elements from the transposon into this fractured gene with the RAG enzymes, which sparked the generation of an incalculable number of new proteins. To repair the fracture, the cell called in specialized machinery—double strand break repair enzymes—to fix the broken strands of genetic material. Proteins encoded by such “rearranged” genes eventually became antibodies—the front line of defense in the adaptive immune response.
Read more on ALS website