Adapting to a changing world: RAG genomics and evolution.

[omenn syndrome]

The origin of the recombination-activating genes (RAGs ) is considered to be a foundation hallmark for adaptive immunity , characterised by the presence of antigen receptor genes that provide the ability to recognise and respond to specific peptide antigens . In vertebrates , a diverse repertoire of antigen-specific receptors , T cell receptors and immunoglobulins is generated by V (D )J recombination performed by the RAG-1 and RAG-2 protein complex . RAG homologues were identified in many jawed vertebrates . Despite their crucial importance , no homologues have been found in jawless vertebrates and invertebrates . This paper focuses on the RAG homologues in humans and other vertebrates for which the genome is completely sequenced , and also discusses the main contribution of the use of RAG homologues in phylogenetics and vertebrate evolution . Since mutations in both genes cause a spectrum of severe combined immunodeficiencies , including the Omenn syndrome (OS ), these topics are discussed in detail . Finally , the relevance to genomic diversity and implications to immunomics are addressed . The search for homologues could enlighten us about the evolutionary processes that shaped the adaptive immune system . Understanding the diversity of the adaptive immune system is crucially important for the design and development of new therapies to modulate the immune responses in humans and /or animal models .