Cloning and characterization of a novel mouse Siglec, mSiglec-F - Differential evolution of the mouse and human (CD33) Siglec-3-related gene clusters
Cloning and characterization of a novel mouse Siglec, mSiglec-F - Differential evolution of the mouse and human (CD33) Siglec-3-related gene clusters
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DOI：
10.1074/jbc.m108573200
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发表时间：
2001-11-30
影响因子：
4.8
通讯作者：
Varki, A
中科院分区：
文献类型：
--
作者：
Angata, T;Hingorani, R;Varki, A
一种属于Siglec - 3相关Siglecs亚家族的新型小鼠Siglec（mSiglec - F）已被克隆并鉴定。与大多数具有混杂连接特异性的人Siglec - 3（hSiglec - 3）相关Siglecs不同，mSiglec - F对α2 - 3连接的唾液酸表现出强烈的偏好。它主要在骨髓单核细胞谱系的未成熟细胞以及某些组织中的一部分CD11b（Mac - 1）阳性细胞中表达。与先前克隆的Siglec - 3相关的mSiglecs一样，由于与单一的人Siglec缺乏很强的序列相似性，使得人同源基因的鉴定变得困难。因此，我们对人和小鼠基因组之间的Siglecs进行了全面比较。小鼠基因组包含8个Siglec基因，而人基因组包含11个Siglec基因和1个Siglec样基因。尽管人源和鼠源的Siglecs 1、2和4之间的一一对应同源关系得到了确认，但Siglec - 3相关的Siglecs在人和小鼠之间表现出显著差异。我们在小鼠7号染色体上与人类19号染色体上Siglec - 3相关基因簇同源的区域仅发现了4个Siglec基因和2个假基因，而人类19号染色体上该区域包含7个Siglec基因、1个Siglec样基因和13个假基因。尽管对基因图谱和外显子结构的分析允许对小鼠 - 人Siglec同源对进行初步指定，但不等遗传重组的可能性使得这种指定不具有确定性。因此，我们支持对其他小鼠Siglecs采用临时的字母命名法。目前的信息表明，mSiglec - F可能是人Siglec - 5的同源基因。先前报道的mSiglec - 3/CD33和mSiglec - E/MIS可能分别是人Siglec - 3和人Siglec - 9的同源基因。该基因簇中的另一个Siglec - 3样基因（mSiglec - G）可能是人Siglec - 10的同源基因。另一个小鼠基因（mSiglec - H）没有明显的人同源基因，位于该基因簇之外。因此，尽管Siglec - 3相关基因的一些重复发生在灵长类和啮齿类谱系分离之前（约8000 - 1亿年前），但此后该基因簇在灵长类谱系中经历了大量的重复。
A novel mouse Siglec (mSiglec-F) belonging to the subfamily of Siglec-3-related Siglecs has been cloned and characterized. Unlike most human Siglec-3 (hSiglec-3)-related Siglecs with promiscuous linkage specificity, mSiglec-F shows a strong preference for alpha2-3-linked sialic acids. It is predominantly expressed in immature cells of the myelomonocytic lineage and in a subset of CD11b (Mac-1)-positive cells in some tissues. As with previously cloned Siglec-3-related mSiglecs, the lack of strong sequence similarity to a singular hSiglec made identification of the human ortholog difficult. We therefore conducted a comprehensive comparison of Siglecs between the human and mouse genomes. The mouse genome contains eight Siglec genes, whereas the human genome contains 11 Siglec genes and a Siglec-like gene. Although a one-to-one orthologous correspondence between human and mouse Siglecs 1, 2, and 4 is confirmed, the Siglec-3-related Siglecs showed marked differences between human and mouse. We found only four Siglec genes and two pseudogenes in the mouse chromosome 7 region syntenic to the Siglec-3-related gene cluster on human chromosome 19, which, in contrast, contains seven Siglec genes, a Siglec-like gene, and thirteen pseudogenes. Although analysis of gene maps and exon structures allows tentative assignments of mouse-human Siglec ortholog pairs, the possibility of unequal genetic recombination makes the assignments inconclusive. We therefore support a temporary lettered nomenclature for additional mouse Siglecs. Current information suggests that mSiglec-F is likely a hSiglec-5 ortholog. The previously reported mSiglec-3/CD33 and mSiglec-E/MIS are likely orthologs of hSiglec-3 and hSiglec-9, respectively. The other Siglec-3-like gene in the cluster (mSiglec-G) is probably a hSiglec-10 ortholog. Another mouse gene (mSiglec-H), without an apparent human ortholog, lies outside of the cluster. Thus, although some duplications of Siglec-3-related genes predated separation of the primate and rodent lineages (about 80-100 million years ago), this gene cluster underwent extensive duplications in the primate lineage thereafter.