An analysis of IGFBP evolution.
OBJECTIVE
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.


CONCLUSIONS
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.
University of Virginia Children's Hospital, Department of Pediatrics, P.O. Box 800386, Charlottesville, VA 22908, United States. pvgordon@ochsner.org
Phillip V
PV
Gordon
Marek
M
Marcinkiewicz
D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D017353:Gene Deletion; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D018969:Insulin-Like Growth Factor Binding Proteins