Evolution of the Insulin-Like Growth Factor Binding Protein (IGFBP) Family
Evolution of the Insulin-Like Growth Factor Binding Protein (IGFBP) Family
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DOI：
10.1210/en.2011-0047
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发表时间：
2011-06-01
期刊：
影响因子：
4.8
通讯作者：
Larhammar, Dan
中科院分区：
文献类型：
--
作者：
Daza, Daniel Ocampo;Sundstrom, Gorel;Larhammar, Dan
IGF结合蛋白（IGFBP）基因家族的进化一直难以解决。染色体和连续复制都被认为是这个基因家族扩展的机制。我们已经确定并注释了IGFBP序列，从广泛的选择脊椎动物物种以及Branchiostoma floridae和玻璃海鞘。通过结合详细的序列分析与基于序列的同源性和染色体信息，我们得出以下情况：祖先的脊索动物IGFBP基因进行了局部基因复制，导致一个基因对相邻的HOX簇。随后，该基因家族在两个基础脊椎动物四倍化（2R）中扩展，导致目前在胎盘哺乳动物中发现的六种IGFBP类型。硬骨鱼的祖先经历了第三次四倍化（3R），进一步扩大了IGFBP的剧目。这五个已测序的硬骨鱼基因组保留了9 - 11个IGFBP基因。这种情况得到了HOX基因区域中三个相邻基因家族（即表皮生长因子受体（EGFR）和Ikaros和无远端（DLX）转录因子）的同源性的支持。我们的序列比较表明，IGFBPs中的几个重要结构组分是在所有直系同源物中保持的祖先脊椎动物特征，例如IGFBP-2中的整合素相互作用基序Arg-Gly-Asp。相反，IGFBP-1中的Arg-Gly-Asp基序在哺乳动物中独立出现。IGFBP基因家族在古代扩展后的大程度保留强烈表明，每个基因在脊椎动物进化的早期就进化出了独特而重要的功能。（内分泌学152：2278 - 2289，2011）
The evolution of the IGF binding protein (IGFBP) gene family has been difficult to resolve. Both chromosomal and serial duplications have been suggested as mechanisms for the expansion of this gene family. We have identified and annotated IGFBP sequences from a wide selection of vertebrate species as well as Branchiostoma floridae and Ciona intestinalis. By combining detailed sequence analysis with sequence-based phylogenies and chromosome information, we arrive at the following scenario: the ancestral chordate IGFBP gene underwent a local gene duplication, resulting in a gene pair adjacent to a HOX cluster. Subsequently, the gene family expanded in the two basal vertebrate tetraploidization (2R) resulting in the six IGFBP types that are presently found in placental mammals. The teleost fish ancestor underwent a third tetraploidization (3R) that further expanded the IGFBP repertoire. The five sequenced teleost fish genomes retain 9-11 of IGFBP genes. This scenario is supported by the phylogenies of three adjacent gene families in the HOX gene regions, namely the epidermal growth factor receptors (EGFR) and the Ikaros and distal-less (DLX) transcription factors. Our sequence comparisons show that several important structural components in the IGFBPs are ancestral vertebrate features that have been maintained in all orthologs, for instance the integrin interaction motif Arg-Gly-Asp in IGFBP-2. In contrast, the Arg-Gly-Asp motif in IGFBP-1 has arisen independently in mammals. The large degree of retention of IGFBP genes after the ancient expansion of the gene family strongly suggests that each gene evolved distinct and important functions early in vertebrate evolution. (Endocrinology 152: 2278-2289, 2011)