An analysis of IGFBP evolution.

OBJECTIVES

To perform a synonymous, non-synonymous codon mutational analysis of the IGFBP gene family and identify mechanisms by which the IGFBP subfamilies diverged.

METHODS

We identified 78 intact nucleotide sequences from 6 IGFBP subfamilies and 12 different species and used them for phylogenetic and synonymous, non-synonymous codon mutational analysis. Deletion and insertion comparisons were performed across subfamilies to determine if this might play a unique role in subfamily genesis.

RESULTS

IGFBP-2 was identified by phylogenetic analysis to be the most related subfamily of the IGFBP progenitor, followed by IGFBP-4. Insertions and deletions within the variable domains were associated with divergence of each subfamily from its progenitor, suggesting a common motif for IGFBP evolution. Insertions unique to mammals were also found within the amino terminus of IGFBP-2.

CONCLUSION

IGFBP subfamily divergence is associated with variable domain insertion or deletion and vigorous non-synonymous codon mutation. Our findings suggest strong selective pressure for IGFBP divergence in terrestrial vertebrates.