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Related Experiment Videos

Interpreting mammalian evolution using Fugu genome comparisons.

Ivan Ovcharenko1, Lisa Stubbs, Gabriela G Loots

  • 1Genome Biology Division, Lawrence Livermore National Laboratory, 7000 East Avenue, L-441, Livermore, CA 94550, USA. ovcharenko1@llnl.gov

Genomics
|October 12, 2004
PubMed
Summary

Comparing human, Fugu, and mouse genomes reveals specific conservation patterns. This helps identify novel mammalian transcriptional regulatory elements, improving our understanding of gene regulation.

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Area of Science:

  • Comparative genomics
  • Evolutionary biology
  • Regulatory element discovery

Background:

  • Evolutionarily conserved noncoding elements between humans and Fugu demonstrate tissue-specific enhancer activity in vivo.
  • Distant genomic comparisons can identify specific classes of regulatory elements.
  • Mammalian-specific regulatory elements require refined identification methods.

Purpose of the Study:

  • To define conservation criteria for discovering transcriptional regulatory elements specific to mammals.
  • To leverage human/Fugu and human/mouse conservation patterns for regulatory element identification.

Main Methods:

  • Genome-scale comparisons of noncoding human/Fugu evolutionary conserved elements (ECRs).
  • Comparison of human/mouse ECRs with human/Fugu ECRs.

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  • Defining conservation thresholds based on length and sequence identity.

    • Main Results:

    • A specific signature for human/mouse ECRs (>or=350 bp long, >or=77% identity) conserved in fishes was identified.
    • This threshold successfully identifies 90% of all human/Fugu noncoding ECRs.
    • The method efficiently filters for functional human/mouse ECRs without needing human-Fugu alignments.

    Conclusions:

    • Juxtaposing cross-species conservation patterns is effective for identifying mammalian-specific regulatory elements.
    • A defined conservation threshold provides an efficient filter for functional regulatory elements.
    • This approach enhances the discovery of tissue-specific transcriptional enhancers.