Cao Huan, de Bono Bernard, Belov Katherine, Wong Emily S, Trowsdale John, Barrow Alexander David
Cambridge Institute for Medical Research, Wellcome Trust/MRC Building Addenbrooke's Hospital, Cambridge, UK.
Immunogenetics. 2009 May;61(5):401-17. doi: 10.1007/s00251-009-0372-0. Epub 2009 Apr 1.
The CD33-related sialic acid binding Ig-like lectins (CD33rSiglecs) are predominantly inhibitory receptors expressed on leukocytes. They are distinguishable from conserved Siglecs, such as Sialoadhesin and MAG, by their rapid evolution. A comparison of the CD33rSiglec gene cluster in different mammalian species showed that it can be divided into subclusters, A and B. The two subclusters, inverted in relation to each other, each encode a set of CD33rSiglec genes arranged head-to-tail. Two regions of strong correspondence provided evidence for a large-scale inverse duplication, encompassing the framework CEACAM-18 (CE18) and ATPBD3 (ATB3) genes that seeded the mammalian CD33rSiglec cluster. Phylogenetic analysis was consistent with the predicted inversion. Rodents appear to have undergone wholesale loss of CD33rSiglec genes after the inverse duplication. In contrast, CD33rSiglecs expanded in primates and many are now pseudogenes with features consistent with activating receptors. In contrast to mammals, the fish CD33rSiglecs clusters show no evidence of an inverse duplication. They display greater variation in cluster size and structure than mammals. The close arrangement of other Siglecs and CD33rSiglecs in fish is consistent with a common ancestral region for Siglecs. Expansion of mammalian CD33rSiglecs appears to have followed a large inverse duplication of a smaller primordial cluster over 180 million years ago, prior to eutherian/marsupial divergence. Inverse duplications in general could potentially have a stabilizing effect in maintaining the size and structure of large gene clusters, facilitating the rapid evolution of immune gene families.
与CD33相关的唾液酸结合免疫球蛋白样凝集素（CD33rSiglecs）主要是在白细胞上表达的抑制性受体。它们因其快速进化而与保守的Siglecs（如唾液酸黏附素和髓鞘相关糖蛋白）有所区别。对不同哺乳动物物种中CD33rSiglec基因簇的比较表明，它可分为A和B两个亚簇。这两个亚簇彼此反向排列，各自编码一组首尾相连排列的CD33rSiglec基因。两个高度对应的区域为大规模反向重复提供了证据，该重复涵盖了为哺乳动物CD33rSiglec基因簇提供种子的框架CEACAM - 18（CE18）和ATPBD3（ATB3）基因。系统发育分析与预测的反向重复一致。啮齿动物似乎在反向重复后经历了CD33rSiglec基因的全面丢失。相比之下，CD33rSiglecs在灵长类动物中有所扩展，现在许多都是具有与激活受体一致特征的假基因。与哺乳动物不同，鱼类的CD33rSiglecs基因簇没有反向重复的证据。它们在基因簇大小和结构上的变化比哺乳动物更大。鱼类中其他Siglecs和CD33rSiglecs的紧密排列与Siglecs的共同祖先区域一致。哺乳动物CD33rSiglecs的扩展似乎是在1.8亿多年前真兽类/有袋类分歧之前，一个较小的原始基因簇发生大规模反向重复之后发生的。一般来说，反向重复可能在维持大型基因簇的大小和结构方面具有稳定作用，促进免疫基因家族的快速进化。
