Journal of Molecular Evolution

, Volume 62, Issue 1, pp 73–88 | Cite as

Primate-Specific Endogenous Cis-Antisense Transcription in the Human 5q31 Protocadherin Gene Cluster

  • Leonard Lipovich
  • Ravi Raj Vanisri
  • Say Li Kong
  • Chin-Yo Lin
  • Edison T. Liu
Article
First Online:
Received:
Accepted:

Abstract

Protocadherins (PCDH), localized to synaptic junctions, contribute to the formation of neuronal networks during brain development; thus, it is speculated that protocadherins may play a role in evolution of neuronal complexity. While protocadherin genes are highly conserved in vertebrates, EST evidence from the locus suggests apparently species-specific cis-antisense transcripts. Novel cis-antisense transcripts, which partially overlap the PCDHα12 variable exon, PCDHβ3 single-exon gene, and PCDHψ5 unprocessed pseudogene in the human 5q31 PCDHα/β/γ gene cluster and which are coexpressed with sense-strand transcripts in fetal and adult brain, were identified computationally and validated by gene-specific strand-specific reverse transcriptase PCR (SSRTPCR) and sequencing. Absence of antisense transcripts arising from equivalent genomic locations in mouse indicates that the antisense transcripts originated in the primates after the primate-rodent divergence. Furthermore, not all expected orthologues of human sense and antisense PCDH transcripts were detected in rhesus macaque brain, implying that protocadherin expression patterns differ between primate species. RT followed by quantitative real-time PCR (QPCR) analysis of the three genes in the brain of all three species, and of the PCDHβ15 gene paralogous to PCDHψ5 in human and rhesus, revealed that the presence of antisense transcripts was significantly associated with lower sense expression levels across all orthologues. This inverse relationship, along with the pattern of sense and antisense coexpression in the brain, is consistent with a regulatory role for the primate-specific PCDH cis-antisense transcripts, which may represent recent evolutionary inventions modulating the activity of this conserved gene cluster.

Keywords

Protocadherin Antisense Primate-specific Gene birth Noncoding RNA 
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Notes

Acknowledgments

This work was funded in its entirety by the Agency for Science, Technology, and Research, Republic of Singapore, through Genome Institute of Singapore budget no. GIS/03-114102. We thank Zhang Tao for fruitful discussions of SSRTPCR artifacts and the ThermoScript protocol and Sanjay Gupta and Jane Thomsen for expert assistance with Northern blotting.

Supplementary material

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Supplementary material

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Leonard Lipovich
    • 1
  • Ravi Raj Vanisri
    • 1
  • Say Li Kong
    • 1
  • Chin-Yo Lin
    • 1
  • Edison T. Liu
    • 1
  1. 1.Genome Institute of SingaporeSingaporeSingapore

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