Models for the recent evolution of protocadherin gene clusters.

The clustered protocadherins (Pcdhs) are single-pass transmembrane proteins that constitute a subfamily within the cadherin superfamily. In mammals, they are arranged in three consecutive clusters named alpha, beta, and gamma. These proteins are expressed in the nervous system and are targeted to mature synapses. Interestingly, different neurons express different subsets of isoforms; however, little is known about the functions and expression of the clustered Pcdhs. Previous phylogenetic analyses that compared rodent and human clusters postulated the recent occurrence of gene duplication events. Using standard phylogenetic methods, I confirmed the prior observations, and I show that duplications are likely to occur through unequal crossing-over events between two, and sometimes three, different Pcdh genes. The results are consistent with the fact that these genes undergo gene conversion. Recombination events between different clustered Pcdh genes appear to underlie concerted evolution through gene conversion and gene duplications through unequal crossing-over. In this work, I provided evidence that the unit of duplication of these genes in both the mouse and the human and within each cluster is the same. The unit of duplication includes the extracellular domain-coding sequence of an isoform and its promoter along with the cytoplasmic domain-coding region of the immediately upstream isoform in the cluster.