PUBLICATION

Comparative Genomics and Diversifying Selection of the Clustered Vertebrate Protocadherin Genes

Authors
Wu, Q.
ID
ZDB-PUB-050308-4
Date
2005
Source
Genetics   169(4): 2179-2188 (Journal)
Registered Authors
Keywords
protocadherin, comparative genomics, diversifying selection, neuronal connection, alternative splicing
MeSH Terms
  • Brain/metabolism
  • Models, Molecular
  • Multigene Family
  • Pan troglodytes
  • Animals
  • Phylogeny
  • Zebrafish
  • Humans
  • Exons
  • Genetic Variation
  • Genomics/methods*
  • Models, Genetic
  • Phenotype
  • Cloning, Molecular
  • Cadherins/genetics*
  • Cell Membrane/metabolism
  • Rats
  • Codon
  • Cell Lineage
  • DNA, Complementary/metabolism
  • Alternative Splicing
  • Protein Structure, Tertiary
  • Mice
  • Molecular Sequence Data
  • Evolution, Molecular
(all 25)
PubMed
15744052 Full text @ Genetics
Abstract
To explain the mechanism for specifying diverse neuronal connections in the brain, Sperry proposed that individual cells carry chemoaffinity tags on their surfaces. The enormous complexity of these connections requires a tremendous diversity of cell-surface proteins. A large number of neural transmembrane protocadherin (Pcdh) proteins is encoded by three closely-linked human and mouse gene clusters (alpha, beta, and gamma). To gain insight into Pcdh evolution, I performed comprehensive comparative cDNA and genomic DNA analyses for the three clusters in the chimpanzee, rat, and zebrafish genomes. I found that there are species-specific duplications in vertebrate Pcdh genes, and that additional diversity is generated through alternative splicing within the zebrafish "variable" and "constant" regions. Moreover, different codons (sites) in the mammalian Pcdh ectodomains (ECs) are under diversifying selection, with some under diversity-enhancing positive Darwinian selection and others, including calcium-binding sites, under strong purifying selection. Interestingly, almost all positively selected codon positions are located on the surface of ECs 2 and 3. These diversified residues likely play an important role in combinatorial interactions of Pcdh proteins, which could provide the staggering diversity required for neuronal connectivities in the brain. These results also suggest that adaptive selection is an additional evolutionary factor for increasing Pcdh diversity.
Genes / Markers
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Phenotype
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Human Disease / Model
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Fish
Fish
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