ArticleGenetics2005
Comparative genomics and diversifying selection of the clustered vertebrate protocadherin genes.
Article in Genetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 97 citations in OpenAlex.
- Adhesion-Based Self-Organization in Tissue Patterning.Annual review of cell and developmental biology · 2022Review
- Mosaic and non-mosaic protocadherin 19 mutation leads to neuronal hyperexcitability in zebrafish.Neurobiology of disease · 2022Article
- The Conserved Serine Transporter SdaC Moonlights To Enable Self Recognition.Journal of bacteriology · 2022Article
- Wiring the Brain by Clustered Protocadherin Neural Codes.Neuroscience bulletin · 2021Review
- Expression of protocadherin-γC4 protein in the rat brain.The Journal of comparative neurology · 2020Article
- An Investigation of ZZ/ZW and XX/XY Sex Determination Systems in North African Catfish (Frontiers in genetics · 2020Article
- Clustered Protocadherins Emerge as Novel Susceptibility Loci for Mental Disorders.Frontiers in neuroscience · 2020Review
- Interaction specificity of clustered protocadherins inferred from sequence covariation and structural analysis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Germline Structural Variations Are Preferential Sites of DNA Replication Timing Plasticity during Development.Genome biology and evolution · 2019Article
- Article
- Ancestral Variations of the PCDHG Gene Cluster Predispose to Dyslexia in a Multiplex Family.EBioMedicine · 2018Article
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- Characterization of a Single Genomic Locus Encoding the Clustered Protocadherin Receptor Diversity in Xenopus tropicalis.G3 (Bethesda, Md.) · 2016Article
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- Functional test of PCDHB11, the most human-specific neuronal surface protein.BMC evolutionary biology · 2016Article
- Structure and Sequence Analyses of Clustered Protocadherins Reveal Antiparallel Interactions that Mediate Homophilic Specificity.Structure (London, England : 1993) · 2015Article
- Article
- Efficient inversions and duplications of mammalian regulatory DNA elements and gene clusters by CRISPR/Cas9.Journal of molecular cell biology · 2015Article
- Protocadherins branch out: Multiple roles in dendrite development.Cell adhesion & migration · 2015Review
- Sorting out a promiscuous superfamily: towards cadherin connectomics.Trends in cell biology · 2014Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 connections in the brain. These results also suggest that adaptive selection is an additional evolutionary factor for increasing Pcdh diversity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.