Farber Steven A, De Rose Robert A, Olson Eric S, Halpern Marnie E
Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland 21210, USA.
Genome Res. 2003 Jun;13(6A):1082-96. doi: 10.1101/gr.479603.
The Annexins (ANXs) are a family of calcium- and phospholipid-binding proteins that have been implicated in many cellular processes, including channel formation, membrane fusion, vesicle transport, and regulation of phospholipase A2 activity. As a first step toward understanding in vivo function, we have cloned 11 zebrafish anx genes. Four genes (anx1a, anx2a, anx5,and anx11a) were identified by screening a zebrafish cDNA library with a Xenopus anx2 fragment. For these genes, full-length cDNA sequences were used to cluster 212 EST sequences generated by the Zebrafish Genome Resources Project. The EST analysis revealed seven additional anx genes that were subsequently cloned. The genetic map positions of all 11 genes were determined by using a zebrafish radiation hybrid panel. Sequence and syntenic relationships between zebrafish and human genes indicate that the 11 genes represent orthologs of human anx1,2,4,5,6,11,13,and suggest that several zebrafish anx genes resulted from duplications that arose after divergence of the zebrafish and mammalian genomes. Zebrafish anx genes are expressed in a wide range of tissues during embryonic and larval stages. Analysis of the expression patterns of duplicated genes revealed both redundancy and divergence, with the most similar genes having almost identical tissue-specific patterns of expression and with less similar duplicates showing no overlap. The differences in gene expression of recently duplicated anx genes could explain why highly related paralogs were maintained in the genome and did not rapidly become pseudogenes.
膜联蛋白（ANXs）是一类钙结合和磷脂结合蛋白家族，涉及许多细胞过程，包括通道形成、膜融合、囊泡运输以及磷脂酶A2活性的调节。作为了解其体内功能的第一步，我们克隆了11个斑马鱼anx基因。通过用非洲爪蟾anx2片段筛选斑马鱼cDNA文库，鉴定出了4个基因（anx1a、anx2a、anx5和anx11a）。对于这些基因，全长cDNA序列用于对斑马鱼基因组资源计划产生的212个EST序列进行聚类。EST分析揭示了另外7个随后被克隆的anx基因。使用斑马鱼辐射杂种板确定了所有11个基因的遗传图谱位置。斑马鱼和人类基因之间的序列和同线性关系表明，这11个基因代表人类anx1、2、4、5、6、11、13的直系同源物，并表明几个斑马鱼anx基因是斑马鱼和哺乳动物基因组分化后发生的重复所导致的。斑马鱼anx基因在胚胎和幼虫阶段的多种组织中表达。对重复基因表达模式的分析揭示了冗余和差异，最相似的基因具有几乎相同的组织特异性表达模式，而不太相似的重复基因则没有重叠。最近重复的anx基因在基因表达上的差异可以解释为什么高度相关的旁系同源物在基因组中得以保留，而没有迅速成为假基因。
