Molecular phylogenetics and evolution in sharks and fishes
DNA sequences from the recombination-activating gene 1 (RAG1) are being used in a growing number of studies of the phylogenetic relationships of different vertebrate lineages. I have assembled a diverse set of RAG1 sequences from four vertebrate clades and analyzed their evolutionary characteristics to better understand the phylogenetic value of this gene and to delineate regions of the protein that may be functionally important. This analysis showed that RAG1 sequences are subject to variable evolutionary constraints between different sites on the molecule and between different lineages. As a result, substitution characteristics and the rate of evolution of the DNA and amino acid sequences are heterogeneous between and within the vertebrate clades considered here. This heterogeneity must be given consideration when devising phylogenetic analyses based on RAG1 sequences. The comparative sequence analysis highlighted two highly conserved regions with no known functions. The first of these is located in the N-terminal end of the molecule and is restricted to bony vertebrates. The second is conserved in all known sequences and contains three pairs of closely spaced cysteine residues. In addition, the fish sequences examined show some unique features not observed in other vertebrates. The regions delineated by sequence comparison should help guide studies of RAG 1 function, which is critical in the development of the adaptive immune system through its mediation of the mechanism of antigen receptor loci rearrangement known as V(D)J recombination.