Karavanich C, Anholt R R
Department of Zoology, North Carolina State University, Raleigh 27695-7617, USA.
Ann N Y Acad Sci. 1998 Nov 30;855:294-300. doi: 10.1111/j.1749-6632.1998.tb10585.x.
Olfactomedin is a glycosylated extracellular matrix protein originally identified at the mucociliary surface of the amphibian olfactory neuroepithelium and subsequently localized throughout the mammalian central nervous system. Although olfactomedin homologues have been identified in fish, frog, rat, mouse and human, its function is still unknown. As a first step toward elucidating the function of olfactomedin, sequences of teleost, amphibian and human homologues were compared to identify invariant, and hence, potential functionally important motifs. Previous studies revealed 33% amino acid sequence identity between rat and frog olfactomedin in their carboxyl terminal segments. Further analysis, however, reveals more extensive homologies throughout the molecule. Despite significant sequence divergence, cysteines essential for homo-polymer formation, such as the CXC motif near the amino terminus, are conserved as is the characteristic glycosylation pattern, suggesting that these posttranslational modifications are essential for function. Furthermore, alignment of a region of 53 amino acids of fish, frog, rat and human olfactomedin reveals seven invariant residues including a negatively charged cluster of aspartic and glutamic acid residues. Molecular evolutionary genetic analysis reveals an accelerated rate of nucleotide substitutions in the mammalian lineage. The evolutionary rate at the protein level, however, is constant, indicating that evolution of olfactomedin is constrained by structural limitations. Whereas considerable evolutionary divergence is evident between fish, frog and mammalian olfactomedins, olfactomedins of rat and human show 98% amino acid sequence identity. It appears that an ancestral olfactomedin gene arose before the evolution of terrestrial vertebrates and evolved independently in teleost, amphibian and mammalian lineages. The apparent evolutionary pressure toward conservation of primary structure supports the notion that olfactomedin has an important function in the mammalian nervous system.
嗅觉介质是一种糖基化的细胞外基质蛋白，最初在两栖动物嗅觉神经上皮的黏液纤毛表面被鉴定出来，随后在整个哺乳动物中枢神经系统中定位。尽管在鱼类、青蛙、大鼠、小鼠和人类中都发现了嗅觉介质同源物，但其功能仍然未知。作为阐明嗅觉介质功能的第一步，对硬骨鱼、两栖动物和人类同源物的序列进行了比较，以确定不变的，从而潜在功能重要的基序。先前的研究表明，大鼠和青蛙嗅觉介质在其羧基末端片段中有33%的氨基酸序列同一性。然而，进一步分析发现整个分子中存在更广泛的同源性。尽管序列差异很大，但对于同聚物形成至关重要的半胱氨酸，如氨基末端附近的CXC基序，以及特征性糖基化模式都得以保留，这表明这些翻译后修饰对功能至关重要。此外，对鱼类、青蛙、大鼠和人类嗅觉介质53个氨基酸区域的比对揭示了七个不变残基，包括一个由天冬氨酸和谷氨酸残基组成的带负电荷簇。分子进化遗传分析表明，哺乳动物谱系中的核苷酸替换速率加快。然而，蛋白质水平的进化速率是恒定的，这表明嗅觉介质的进化受到结构限制。虽然鱼类、青蛙和哺乳动物的嗅觉介质之间存在明显的进化差异，但大鼠和人类的嗅觉介质显示出98%的氨基酸序列同一性。看来，一个祖先嗅觉介质基因在陆生脊椎动物进化之前就已出现，并在硬骨鱼、两栖动物和哺乳动物谱系中独立进化。对一级结构保守性的明显进化压力支持了嗅觉介质在哺乳动物神经系统中具有重要功能这一观点。
