Evolution of the Class 2 cytokines and receptors, and discovery of new friends and relatives.

The sequencing of a wide variety of genomes and their transcripts has allowed researchers to determine how proteins or protein families evolved and how strongly during evolution a protein has been conserved. In this report, we analyze the evolution of the Class 2 ligands and their cognate receptors by analyzing Class 2 ligand and receptor chain gene sequences from a variety of DNA sequence databases. Both the Class 2 cytokines and receptor chains appear to have developed during the evolution of the chordate phyla: distant homologues of type I interferon (IFN) receptors are the only Class 2 cytokine receptors identified in the Ciona genomes, while a wide variety of Class 2 ligands and receptor chains are encoded in the currently available genomes of bony vertebrates (teleost fish, amphibians, reptiles, birds, mammals). Phylogenetic trees of ligands and ligand-binding receptor chains demonstrate that proteins involved in conferring antiviral activity diverged before those involved in adaptive immunity. Genes encoding IFNs and IFN receptors duplicated multiple times during chordate evolution, suggesting that duplication of genes encoding IFN activity conveyed an evolutionary advantage. Altogether, these data support a model whereby the original Class 2 cytokines and receptors evolved and duplicated during the evolution of the chordate innate immune response system; new receptor and ligand duplications evolved into signaling molecules to fulfill communication requirements of a highly specialized and differentiated vertebrate immune system. In addition, the genomic analysis led to the discovery of some new members of this family.