Adapting to a changing world: <it>RAG </it>genomics and evolution

• Main Authors: de Camargo Maristela, Nahum Laila
• Format: Article
• Language: English
• Published: BMC 2005-06-01
• Series: Human Genomics
• Subjects: adaptive immune system; recombination-activating genes; human genome; animal models; vertebrate phylogeny; evolutionary genomics
• Online Access: http://www.humgenomics.com/content/2/2/132

<p>Abstract</p> <p>The origin of the recombination-activating genes (<it>RAG</it>s) 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. <it>RAG </it>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 <it>RAG </it>homologues in humans and other vertebrates for which the genome is completely sequenced, and also discuses the main contribution of the use of <it>RAG </it>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.</p>