Genome-wide reverse genetics framework to identify novel functions of the vertebrate secretome

PLoS One. 2006 Dec 20;1(1):e104. doi: 10.1371/journal.pone.0000104.


Background: Understanding the functional role(s) of the more than 20,000 proteins of the vertebrate genome is a major next step in the post-genome era. The approximately 4,000 co-translationally translocated (CTT) proteins - representing the vertebrate secretome - are important for such vertebrate-critical processes as organogenesis. However, the role(s) for most of these genes is currently unknown.

Results: We identified 585 putative full-length zebrafish CTT proteins using cross-species genomic and EST-based comparative sequence analyses. We further investigated 150 of these genes (Figure 1) for unique function using morpholino-based analysis in zebrafish embryos. 12% of the CTT protein-deficient embryos resulted in specific developmental defects, a notably higher rate of gene function annotation than the 2%-3% estimate from random gene mutagenesis studies.

Conclusion: This initial collection includes novel genes required for the development of vascular, hematopoietic, pigmentation, and craniofacial tissues, as well as lipid metabolism, and organogenesis. This study provides a framework utilizing zebrafish for the systematic assignment of biological function in a vertebrate genome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Antisense Elements (Genetics) / genetics
  • Base Sequence
  • Blood Vessels / embryology
  • Computational Biology
  • Genome
  • Genomics
  • Hematopoiesis
  • Lipid Metabolism / genetics
  • Molecular Sequence Data
  • Proteome
  • Proteomics
  • Sequence Alignment
  • Vertebrates / genetics*
  • Vertebrates / growth & development
  • Vertebrates / physiology
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / physiology
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology


  • Antisense Elements (Genetics)
  • Proteome
  • Zebrafish Proteins