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
-
- Alternative Splicing
- Animals
- Brain/metabolism
- Cadherins/genetics*
- Cell Lineage
- Cell Membrane/metabolism
- Cloning, Molecular
- Codon
- DNA, Complementary/metabolism
- Evolution, Molecular
- Exons
- Genetic Variation
- Genomics/methods*
- Humans
- Mice
- Models, Genetic
- Models, Molecular
- Molecular Sequence Data
- Multigene Family
- Pan troglodytes
- Phenotype
- Phylogeny
- Protein Structure, Tertiary
- Rats
- Zebrafish
- PubMed
- 15744052 Full text @ Genetics
Citation
Wu, Q. (2005) Comparative Genomics and Diversifying Selection of the Clustered Vertebrate Protocadherin Genes. Genetics. 169(4):2179-2188.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping