Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Valencia, Spain.
BMC Evol Biol. 2010 Oct 27;10:331. doi: 10.1186/1471-2148-10-331.
The patterns of emergence and diversification of the families of ubiquitin ligases provide insights about the evolution of the eukaryotic ubiquitination system. U-box ubiquitin ligases (UULs) are proteins characterized by containing a peculiar protein domain known as U box. In this study, the origin of the animal UUL genes is described.
Phylogenetic and structural data indicate that six of the seven main UUL-encoding genes found in humans (UBE4A, UBE4B, UIP5, PRP19, CHIP and CYC4) were already present in the ancestor of all current metazoans and the seventh (WDSUB1) is found in placozoans, cnidarians and bilaterians. The fact that only 4-5 genes orthologous to the human ones are present in the choanoflagellate Monosiga brevicollis suggests that several animal-specific cooptions of the U box to generate new genes occurred. Significantly, Monosiga contains five additional UUL genes that are not present in animals. One of them is also present in distantly-related protozoans. Along animal evolution, losses of UUL-encoding genes are rare, except in nematodes, which lack three of them. These general patterns are highly congruent with those found for other two families (RBR, HECT) of ubiquitin ligases.
Finding that the patterns of emergence, diversification and loss of three unrelated families of ubiquitin ligases (RBR, HECT and U-box) are parallel indicates that there are underlying, linage-specific evolutionary forces shaping the complexity of the animal ubiquitin system.
泛素连接酶家族的出现和多样化模式为真核生物泛素化系统的进化提供了线索。U -box 泛素连接酶（UUL）是一类含有特殊蛋白结构域的蛋白质，该结构域被称为 U -box。本研究描述了动物 UUL 基因的起源。
系统发育和结构数据表明，在人类中发现的 7 个主要 UUL 编码基因中的 6 个（UBE4A、UBE4B、UIP5、PRP19、CHIP 和 CYC4）已经存在于所有后生动物的祖先中，而第 7 个（WDSUB1）则存在于海绵动物、刺胞动物和两侧对称动物中。在领鞭毛虫 Monosiga brevicollis 中，与人类同源的基因只有 4-5 个，这表明 U -box 发生了几次动物特有的基因复制，从而产生了新的基因。值得注意的是，Monosiga 还含有另外 5 个不在动物中存在的 UUL 基因。其中一个也存在于亲缘关系较远的原生动物中。在动物进化过程中，UUL 编码基因的丢失很少见，除了线虫，它们缺少其中的 3 个。这些总体模式与另外两种泛素连接酶家族（RBR、HECT）的发现高度一致。
发现三种不相关的泛素连接酶家族（RBR、HECT 和 U-box）的出现、多样化和丢失模式是平行的，这表明存在着潜在的、与谱系特异性相关的进化力量，这些力量塑造了动物泛素系统的复杂性。
