title: Phylogenetic analysis of the insulin-like growth factor binding protein (IGFBP) and IGFBP-related protein gene families.
abstract: Insulin-like growth factor (IGF) activity is regulated by six high affinity binding proteins (IGFBPs) and possibly by some of the nine IGFBP-related proteins (IGFBP-rPs). To determine the phylogenetic relationship of this proposed gene superfamily, we conducted maximum likelihood (ML) and Bayesian inference analyses on a matrix of amino acid sequences from a diversity of vertebrate species. A single most likely phylogram, ML bootstrap, and Bayesian consensus tree of 10,000,000 generations revealed a monophyletic IGFBP lineage independent of the IGFBP-rPs. The IGFBPs segregated into three distinct clades: IGFBP-1, -3, and -6. Subsequent gene duplication events within the IGFBP-1 and -3 clades resulted in the production and divergence of IGFBP-2 and -4 within the IGFBP-1 clade and IGFBP-5 in the IGFBP-3 clade. By contrast, the IGFBP-rPs were distributed paraphyletically into two clades: IGFBP-rP1, 5, and 6 in one clade and the CCN family (IGFBP-rP2-4,7-9) in another. A recently identified IGFBP-3 homolog in rainbow trout localized to the IGFBP-2 subclade. Subsequence analysis identified a RGD motif common to IGFBP-2 orthologs, but did not identify the nuclear localization sequence present in IGFBP-3 and -5 homologs. The putative trout IGFBP-3 was 36-55% identical to different IGFBP-2 proteins, but only 24-27% identical to IGFBP-3 proteins. These results suggest that the IGFBPs and IGFBP-rPs are at best distantly related and that the limited similarities likely resulted from exon shuffling. They also suggest that rainbow trout, and possibly other salmonids, possess two IGFBP-2 paralogs as the putative trout IGFBP-3 is misannotated.
authors.affiliation: Department of Animal Sciences, Washington State University, Pullman, WA 99164-6351, USA. danrodgers@wsu.edu
authors.forename: Buel D
authors.initials: BD
authors.lastname: Rodgers
authors.forename: Eric H
authors.initials: EH
authors.lastname: Roalson
authors.forename: Cullen
authors.initials: C
authors.lastname: Thompson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D017686:Oncorhynchus mykiss / Q000235:genetics; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins