Phillip V Gordon1, Marek Marcinkiewicz. 1. University of Virginia Children's Hospital, Department of Pediatrics, P.O. Box 800386, Charlottesville, VA 22908, United States. pvgordon@ochsner.org
Abstract
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.
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.
Authors: M van Kleffens; C A Groffen; N F Dits; D J Lindenbergh-Kortleve; A G Schuller; S L Bradshaw; J E Pintar; E C Zwarthoff; S L Drop; J W van Neck Journal: Endocrinology Date: 1999-12 Impact factor: 4.736