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Related Experiment Videos

Evolutionarily conserved and diverged alternative splicing events show different expression and functional profiles.

Zhengyan Kan1, Philip W Garrett-Engele, Jason M Johnson

  • 1Rosetta Inpharmatics LLC, Merck & Co., Inc. 401 Terry Ave N, Seattle, WA 98109, USA.

Nucleic Acids Research
|October 1, 2005
PubMed
Summary

Conserved alternative splicing is highly regulated in humans and mice, particularly in brain signaling pathways. Non-functional splicing is more common in testis and cell lines, potentially due to stress and rapid proliferation.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Alternative splicing significantly increases proteomic diversity.
  • Understanding the functional impact of alternative splicing requires comparative analysis across species.

Purpose of the Study:

  • To classify alternative splicing events based on evolutionary conservation.
  • To investigate the functional implications of conserved and diverged alternative splicing.

Main Methods:

  • Comparative analysis of 10,818 human and mouse gene pairs.
  • Classification of alternative splicing events by genome and transcript conservation.
  • Integration with Gene Ontology (GO) and gene expression data from 52 human tissues/cell lines.

Main Results:

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  • Strong correlation in expression levels of conserved alternative splices between human and mouse.
  • 43% of mouse alternative splices were not found in human transcripts, but 5/11 predictions were observed in human tissues.
  • Conserved alternative splicing is enriched in brain-expressed signaling pathways.
  • Diverged alternative splicing is prevalent in testis and cancer cell lines, associated with stress and proliferation pathways.

Conclusions:

  • Mouse transcripts are valuable for identifying human alternative splicing events.
  • Conserved alternative splicing enhances functional capacity, especially in the central nervous system.
  • Diverged splicing may indicate non-functional events in specific cellular contexts like testis and cancer cell lines.