Boocock G R B, Marit M R, Rommens J M
Program in Genetics and Genomic Biology, The Hospital for Sick Children, 101 College Street, East Tower, Toronto, Canada ON M5G 1L7.
Genomics. 2006 Jun;87(6):758-71. doi: 10.1016/j.ygeno.2006.01.010. Epub 2006 Mar 10.
The Shwachman-Bodian-Diamond syndrome (SBDS) protein family occurs widely in nature, although its function has not been determined. Comprehensive database searches revealed SBDS homologues from 159 species, including examples from all sequenced archaeal and eukaryotic genomes and all eukaryotic kingdoms. Sequence alignment with ClustalX and MUSCLE algorithms led to the identification of conserved residues that occurred predominantly in the amino-terminal FYSH domain where they appeared to contribute to protein folding or stability. Only SBDS residue Gly91 was invariant in all species. Four distantly related protists were found to have two divergent SBDS genes in their genomes. In each case, phylogenetic analyses and the identification of shared sequence features suggested that one gene was derived from lateral gene transfer. We also identified a shared C-terminal zinc finger domain fusion in flowering plants and chromalveolates that may shed light on the function of the protein family and the evolutionary histories of these kingdoms. To assess the extent of SBDS functional conservation, we carried out complementation studies of SBDS homologues and interspecies chimeras in Saccharomyces cerevisiae. We determined that the FYSH domain was widely interchangeable among eukaryotes, while domain 2 imparted species specificity to protein function. Domain 3 was largely dispensable for function in our yeast complementation assay. Overall, the phylogeny of SBDS was shared with a group of proteins that were markedly enriched for RNA metabolism and/or ribosome-associated functions. These findings link Shwachman-Diamond syndrome to other bone marrow failure syndromes with defects in nucleolus-associated processes, including Diamond-Blackfan anemia, cartilage-hair hypoplasia, and dyskeratosis congenita.
施瓦赫曼-博迪安-戴蒙德综合征（SBDS）蛋白家族在自然界广泛存在，但其功能尚未明确。全面的数据库搜索揭示了来自159个物种的SBDS同源物，包括所有已测序古细菌和真核生物基因组以及所有真核生物界的实例。使用ClustalX和MUSCLE算法进行序列比对，从而鉴定出主要出现在氨基末端FYSH结构域中的保守残基，这些残基似乎有助于蛋白质折叠或稳定性。在所有物种中，只有SBDS的甘氨酸91残基是不变的。发现四种亲缘关系较远的原生生物在其基因组中有两个不同的SBDS基因。在每种情况下，系统发育分析和共享序列特征的鉴定表明，其中一个基因源自横向基因转移。我们还在开花植物和色素界生物中鉴定出一个共享的C末端锌指结构域融合，这可能有助于揭示该蛋白家族的功能以及这些生物界的进化历史。为了评估SBDS功能保守的程度，我们在酿酒酵母中对SBDS同源物和种间嵌合体进行了互补研究。我们确定FYSH结构域在真核生物中广泛可互换，而结构域2赋予蛋白质功能物种特异性。在我们的酵母互补试验中，结构域3在很大程度上对功能是可有可无的。总体而言，SBDS的系统发育与一组在RNA代谢和/或核糖体相关功能方面明显富集的蛋白质相同。这些发现将施瓦赫曼-戴蒙德综合征与其他在核仁相关过程中存在缺陷的骨髓衰竭综合征联系起来，包括戴蒙德-布莱克范贫血、软骨毛发发育不全和先天性角化不良。
