Rodgers Buel D, Roalson Eric H, Thompson Cullen
Department of Animal Sciences, Washington State University, Pullman, WA 99164-6351, USA.
Gen Comp Endocrinol. 2008 Jan 1;155(1):201-7. doi: 10.1016/j.ygcen.2007.04.013. Epub 2007 Apr 27.
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.
胰岛素样生长因子（IGF）活性受六种高亲和力结合蛋白（IGFBPs）调控，可能还受九种IGFBP相关蛋白（IGFBP-rPs）中的某些蛋白调控。为确定这个拟议的基因超家族的系统发育关系，我们对来自多种脊椎动物物种的氨基酸序列矩阵进行了最大似然（ML）和贝叶斯推断分析。一个单一的最可能系统发育树、ML自展检验以及经过10,000,000代的贝叶斯共识树显示，IGFBP谱系是单系的，独立于IGFBP-rPs。IGFBPs分为三个不同的进化枝：IGFBP-1、-3和-6。随后在IGFBP-1和-3进化枝内的基因复制事件导致了IGFBP-1进化枝内IGFBP-2和-4以及IGFBP-3进化枝内IGFBP-5的产生和分化。相比之下，IGFBP-rPs呈并系分布于两个进化枝中：一个进化枝包含IGFBP-rP1、5和6，另一个进化枝包含CCN家族（IGFBP-rP2 - 4、7 - 9）。最近在虹鳟中鉴定出的一种IGFBP-3同源物定位于IGFBP-2亚进化枝。后续分析确定了IGFBP-2直系同源物共有的RGD基序，但未鉴定出IGFBP-3和-5同源物中存在的核定位序列。推定的鳟鱼IGFBP-3与不同的IGFBP-2蛋白有36 - 55%的同一性，但与IGFBP-3蛋白只有24 - 27%的同一性。这些结果表明，IGFBPs和IGFBP-rPs充其量只是远缘相关，并表明有限的相似性可能是由外显子重排导致的。它们还表明，虹鳟以及可能的其他鲑科鱼类拥有两个IGFBP-2旁系同源物，因为推定的鳟鱼IGFBP-3被错误注释。
