Abstract
BackgroundThe synaptic cell adhesion molecules, protocadherins, are a vertebrate innovation that accompanied the emergence of the neural tube and the elaborate central nervous system. In mammals, the protocadherins are encoded by three closely-linked clusters (α, β and γ) of tandem genes and are hypothesized to provide a molecular code for specifying the remarkably-diverse neural connections in the central nervous system. Like mammals, the coelacanth, a lobe-finned fish, contains a single protocadherin locus, also arranged into α, β and γ clusters. Zebrafish, however, possesses two protocadherin loci that contain more than twice the number of genes as the coelacanth, but arranged only into α and γ clusters. To gain further insight into the evolutionary history of protocadherin clusters, we have sequenced and analyzed protocadherin clusters from the compact genome of the pufferfish, Fugu rubripes.ResultsFugu contains two unlinked protocadherin loci, Pcdh1 and Pcdh2, that collectively consist of at least 77 genes. The fugu Pcdh1 locus has been subject to extensive degeneration, resulting in the complete loss of Pcdh1γ cluster. The fugu Pcdh genes have undergone lineage-specific regional gene conversion processes that have resulted in a remarkable regional sequence homogenization among paralogs in the same subcluster. Phylogenetic analyses show that most protocadherin genes are orthologous between fugu and zebrafish either individually or as paralog groups. Based on the inferred phylogenetic relationships of fugu and zebrafish genes, we have reconstructed the evolutionary history of protocadherin clusters in the teleost fish lineage.ConclusionOur results demonstrate the exceptional evolutionary dynamism of protocadherin genes in vertebrates in general, and in teleost fishes in particular. Besides the 'fish-specific' whole genome duplication, the evolution of protocadherin genes in teleost fishes is influenced by lineage-specific gene losses, tandem gene duplications and regional sequence homogenization. The dynamic protocadherin clusters might have led to the diversification of neural circuitry among teleosts, and contributed to the behavioral and physiological diversity of teleosts.
Highlights
The synaptic cell adhesion molecules, protocadherins, are a vertebrate innovation that accompanied the emergence of the neural tube and the elaborate central nervous system
The discovery of three closely-linked protocadherin (Pcdh) clusters in mammalian genomes has led to an intriguing speculation that these genes may provide a profound molecular code for specifying neuron-neuron connections in the central nervous system [2,3,4]
The transcription of Pcdh genes is controlled by individual promoters located adjacent to each variable exon [7,8], which contribute to the differential expression patterns of individual Pcdh genes in the central nervous system [5]
Summary
The synaptic cell adhesion molecules, protocadherins, are a vertebrate innovation that accompanied the emergence of the neural tube and the elaborate central nervous system. The protocadherins are encoded by three closely-linked clusters (α, β and γ) of tandem genes and are hypothesized to provide a molecular code for specifying the remarkably-diverse neural connections in the central nervous system. The constant exons encode the main part of the cytoplasmic domain shared by all members in the same cluster [2,3] In many ways, this type of genomic organization resembles the immunoglobulin and T-cell receptor gene loci, which are widely known for their ability to generate a remarkably diverse repertoire of antigen recognizing molecules. Two long-range cis-regulatory elements in Pcdhα cluster have been identified and proposed to underlie the monoallelic expression of the Pcdh genes [10] Taken together, these features of Pcdh genes suggest that they have the potential to play a fundamental role in establishing neural diversity in the brain
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