Duplication and Diversification of the Hypoxia-Inducible IGFBP-1 Gene in Zebrafish

Kamei, H., Lu, L., Jiao, S., Li, Y., Gyrup, C., Laursen, L.S., Oxvig, C., Zhou, J., and Duan, C.
PLoS One   3(8): e3091 (Journal)
Registered Authors
Duan, Cunming
Zebrafish, Hypoxia, Embryos, Gene expression, Sequence motif analysis, Embryogenesis, Evolutionary genetics, Reverse transcriptase-polymerase chain reaction
MeSH Terms
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Conserved Sequence
  • Gene Duplication*
  • Gene Expression Regulation
  • Genetic Variation*
  • Hypoxia/genetics
  • Insulin-Like Growth Factor Binding Protein 1/classification
  • Insulin-Like Growth Factor Binding Protein 1/genetics*
  • Molecular Sequence Data
  • Phylogeny
  • Sequence Alignment
  • Zebrafish/classification
  • Zebrafish/genetics*
  • Zebrafish Proteins/classification
  • Zebrafish Proteins/genetics*
18769480 Full text @ PLoS One
BACKGROUND: Gene duplication is the primary force of new gene evolution. Deciphering whether a pair of duplicated genes has evolved divergent functions is often challenging. The zebrafish is uniquely positioned to provide insight into the process of functional gene evolution due to its amenability to genetic and experimental manipulation and because it possess a large number of duplicated genes. METHODOLOGY/PRINCIPAL FINDINGS: We report the identification and characterization of two hypoxia-inducible genes in zebrafish that are co-ortholgs of human IGF binding protein-1 (IGFBP-1). IGFBP-1 is a secreted protein that binds to IGF and modulates IGF actions in somatic growth, development, and aging. Like their human and mouse counterparts, in adult zebrafish igfbp-1a and igfbp-1b are exclusively expressed in the liver. During embryogenesis, the two genes are expressed in overlapping spatial domains but with distinct temporal patterns. While zebrafish IGFBP-1a mRNA was easily detected throughout embryogenesis, IGFBP-1b mRNA was detectable only in advanced stages. Hypoxia induces igfbp-1a expression in early embryogenesis, but induces the igfbp-1b expression later in embryogenesis. Both IGFBP-1a and -b are capable of IGF binding, but IGFBP-1b has much lower affinities for IGF-I and -II because of greater dissociation rates. Overexpression of IGFBP-1a and -1b in zebrafish embryos caused significant decreases in growth and developmental rates. When tested in cultured zebrafish embryonic cells, IGFBP-1a and -1b both inhibited IGF-1-induced cell proliferation but the activity of IGFBP-1b was significantly weaker. CONCLUSIONS/SIGNIFICANCE: These results indicate subfunction partitioning of the duplicated IGFBP-1 genes at the levels of gene expression, physiological regulation, protein structure, and biological actions. The duplicated IGFBP-1 may provide additional flexibility in fine-tuning IGF signaling activities under hypoxia and other catabolic conditions.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes