Abstract
BACKGROUND: The vertebrate protocadherins are a subfamily of cell adhesion molecules that are predominantly expressed in the nervous system and are believed to play an important role in establishing the complex neural network during animal development. Genes encoding these molecules are organized into a cluster in the genome. Comparative analysis of the protocadherin subcluster organization and gene arrangements in different vertebrates has provided interesting insights into the history of vertebrate genome evolution. Among tetrapods, protocadherin clusters have been fully characterized only in mammals. In this study, we report the identification and comparative analysis of the protocadherin cluster in a reptile, the green anole lizard (Anolis carolinensis). METHODOLOGY/PRINCIPAL FINDINGS: We show that the anole protocadherin cluster spans over a megabase and encodes a total of 71 genes. The number of genes in the anole protocadherin cluster is significantly higher than that in the coelacanth (49 genes) and mammalian (54-59 genes) clusters. The anole protocadherin genes are organized into four subclusters: the delta, alpha, beta and gamma. This subcluster organization is identical to that of the coelacanth protocadherin cluster, but differs from the mammalian clusters which lack the delta subcluster. The gene number expansion in the anole protocadherin cluster is largely due to the extensive gene duplication in the gammab subgroup. Similar to coelacanth and elephant shark protocadherin genes, the anole protocadherin genes have experienced a low frequency of gene conversion. CONCLUSIONS/SIGNIFICANCE: Our results suggest that similar to the protocadherin clusters in other vertebrates, the evolution of anole protocadherin cluster is driven mainly by lineage-specific gene duplications and degeneration. Our analysis also shows that loss of the protocadherin delta subcluster in the mammalian lineage occurred after the divergence of mammals and reptiles. We present a model for the evolutionary history of the protocadherin cluster in tetrapods.