Bioinformatics and Computing Core, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
BMC Evol Biol. 2010 Jan 28;10:30. doi: 10.1186/1471-2148-10-30.
Periostin (POSTN) is a secreted extracellular matrix protein of poorly defined function that has been related to bone and heart development as well as to cancer. In human and mouse, it is known to undergo alternative splicing in its C-terminal region, which is devoid of known protein domains. Differential expression of periostin, sometimes of specific splicing isoforms, is observed in a broad range of human cancers, including breast, pancreatic, and colon cancer. Here, we combine genomic and transcriptomic sequence data from vertebrate organisms to study the evolution of periostin and particularly of its C-terminal region.
We found that the C-terminal part of periostin is markedly more variable among vertebrates than the rest of periostin in terms of exon count, length, and splicing pattern, which we interpret as a consequence of neofunctionalization after the split between periostin and its paralog transforming growth factor, beta-induced (TGFBI). We also defined periostin's sequential 13-amino acid repeat units--well conserved in teleost fish, but more obscure in higher vertebrates--whose secondary structure is predicted to be consecutive beta strands. We suggest that these beta strands may mediate binding interactions with other proteins through an extended beta-zipper in a manner similar to the way repeat units in bacterial cell wall proteins have been reported to bind human fibronectin.
Our results, obtained with the help of the increasingly large collection of complete vertebrate genomes, document the evolutionary plasticity of periostin's C-terminal region, and for the first time suggest a basis for its functional role.
骨膜蛋白（POSTN）是一种分泌型细胞外基质蛋白，其功能尚不清楚，但与骨骼和心脏发育以及癌症有关。在人和小鼠中，已知其 C 端区域发生选择性剪接，该区域缺乏已知的蛋白结构域。骨膜蛋白的表达存在差异，有时是特定剪接异构体的表达存在差异，在包括乳腺癌、胰腺癌和结肠癌在内的广泛人类癌症中都有观察到。在这里，我们结合脊椎动物的基因组和转录组序列数据来研究骨膜蛋白及其 C 端区域的进化。
我们发现，与骨膜蛋白的其余部分相比，骨膜蛋白的 C 端在脊椎动物中在外显子计数、长度和剪接模式方面的变异更为明显，我们将其解释为骨膜蛋白与其旁系同源物转化生长因子，β诱导（TGFBI）分化后的新功能化的结果。我们还定义了骨膜蛋白的连续 13 个氨基酸重复单元——在硬骨鱼中高度保守，但在高等脊椎动物中则更为模糊——其二级结构被预测为连续的β链。我们认为这些β链可能通过扩展的β-拉链与其他蛋白质结合，其方式类似于报道的细菌细胞壁蛋白中的重复单元与人纤维连接蛋白结合的方式。
我们的研究结果得益于越来越多的完整脊椎动物基因组的收集，记录了骨膜蛋白 C 端区域的进化可塑性，并首次提出了其功能作用的基础。
