Sun Yat-sen University released major scientific research results and found the origin of human antibody rearrangement mechanism
Release date: 2016-06-13
Xu Anlong, a professor at Sun Yat-Sen University, discovered the “molecular actinomy stone†of the RAG transposon 600 million years ago and provided the most powerful evidence for the hypothesis of the transposon origin of the human antibody rearrangement mechanism. Related research has recently been published in "Cells".
The body's immune system is divided into two parts: congenital innate immunity and acquired adaptive immunity. The antibody rearrangement mechanism is the most critical mechanism for adaptive immunity, and the most important mechanism for dealing with numerous pathogens (such as the role of vaccines). Mechanisms, therefore, the search for the origin of antibody rearrangement mechanisms has been a hot spot in immunological research. Over the past 40 years, although significant progress has been made in the study of the function and regulation of the core enzyme-antibody rearrangement-activating enzyme (RAG1/RAG2), the hypothesis itself has never been confirmed and has become a classic puzzle that plagues the immunology community.
In order to solve this puzzle, Xu Anlong team first selected the living fossil of animal evolution research - Wenchang fish as the core research object. Because amphioxus is an important species that unveils the origin of vertebrates, and it is found in coastal areas such as Qingdao, Xiamen, and Zhanjiang, providing long-term dependable resources for this research.
After more than a decade of research, the team conducted in-depth informatics analysis of multiple high-quality amphioxus genome sketches and found that amphioxus retains a large number of ancient transposon superfamilies that have long since become extinct in vertebrates. One of the DNA transposon families encodes the RAG1/2 protein and has a terminal inverted repeat TIR similar to the antibody recombination signal sequence RSS, which they named ProtoRAG, which encodes the prototype RAG transposon. Through the study of the functions and mechanisms of the system, they found that the amphioxus ProtoRAG is a long-time search for the RAG transposon that determines the mechanism of antibody rearrangement. It can also be considered that the transposon is a "molecular" left over from the RAG transposon 600 million years ago. Living fossil".
This finding provides strong and direct evidence for the hypothesis of the transposon origin of human antibody rearrangements, and the discovery of this transposon provides a new genetic editing for the future design of new immune antibodies and immune genes using rearrangement mechanisms. Ideas and technology. From the perspective of immunology, the discovery pushes the origin of adaptive immunity from vertebrates to the invertebrate chordate amphioxus, and thus advances 100 million years, rewriting the current immunology textbook on the origin of adaptive immunity. View.
Source: Chinese Journal of Science
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