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.
Gordon
Phillip V
PV
University of Virginia Children's Hospital, Department of Pediatrics, P.O. Box 800386, Charlottesville, VA 22908, United States. pvgordon@ochsner.org
Marcinkiewicz
Marek
M
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