Gel-forming mucins appeared early in metazoan evolution
Gel-forming mucins appeared early in metazoan evolution
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DOI：
10.1073/pnas.0705984104
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发表时间：
2007-10-09
影响因子：
11.1
通讯作者：
Samuelsson, Tore
中科院分区：
文献类型：
--
作者：
Lang, Tiange;Hansson, Gunnar C.;Samuelsson, Tore
粘蛋白是覆盖和保护上皮细胞的蛋白质，其特征在于富含脯氨酸、苏氨酸和丝氨酸的结构域（PTS或粘蛋白结构域）被高度糖基化。由于它们的序列多态性，这些结构域不能用于进化分析。相反，我们利用了典型的粘蛋白的von Willebrand D（VWD）和SEA结构域。对许多动物基因组进行了检查，以确定这些结构域的粘蛋白同源物，并将所得蛋白质的结构域用于系统发育研究。热带非洲爪蟾之所以突出，是因为形成凝胶的粘蛋白的数量明显增加到至少25种，而高等动物只有5种。此外，青蛙Muc2同源物含有独特的PTS结构域，其中半胱氨酸丰富。这种动物还具有一个独特的分泌型粘蛋白样蛋白家族，其具有交替的PTS和SEA结构域，这是一种也在鱼类中鉴定的蛋白质。Muc4粘蛋白的进化似乎是通过从低等动物中存在的含有sushi结构域的蛋白质家族中将PTS结构域募集到AMOP、NIDO和VWD结构域而发生的，并且非洲爪蟾是其中鉴定出与哺乳动物Muc4类似的蛋白质的最深分支的动物。所有的跨膜粘蛋白似乎都出现在脊椎动物谱系中，MUC1粘蛋白仅限于哺乳动物。与此相反，蛋白质的凝胶形成粘蛋白的性质也被确定在星海葵Nematostella vectensis，这表明该组粘蛋白的早期起源。
Mucins are proteins that cover and protect epithelial cells and are characterized by domains rich in proline, threonine, and serine that are heavily glycosylated (PTS or mucin domains). Because of their sequence polymorphism, these domains cannot be used for evolutionary analysis. Instead, we have made use of the von Willebrand D (VWD) and SEA domains, typical for mucins. A number of animal genomes were examined for these domains to identify mucin homologues, and domains of the resulting proteins were used in phylogenetic studies. The frog Xenopus tropicalis stands out because the number of gel-forming mucins has markedly increased to at least 25 as compared with 5 for higher animals. Furthermore, the frog Muc2 homologues contain unique PTS domains where cysteines are abundant. This animal also has a unique family of secreted mucin-like proteins with alternating PTS and SEA domains, a type of protein also identified in the fishes. The evolution of the Muc4 mucin seems to have occurred by recruitment of a PTS domain to AMOP, NIDO, and VWD domains from a sushi domain-containing family of proteins present in lower animals, and Xenopus is the most deeply branching animal where a protein similar to the mammalian Muc4 was identified. All transmembrane mucins seem to have appeared in the vertebrate lineage, and the MUC1 mucin is restricted to mammals. In contrast, proteins with properties of the gel-forming mucins were identified also in the starlet sea anemone Nematostella vectensis, demonstrating an early origin of this group of mucins.