Shannon M, Stubbs L
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
Genomics. 1998 Apr 1;49(1):112-21. doi: 10.1006/geno.1998.5230.
Genetic and physical mapping studies indicate that hundreds of zinc-finger (ZNF)-containing genes populate the human genome and that many of these genes are arranged in familial clusters. However, the extent to which these tandemly arrayed families are conserved among mammalian species is largely unknown. In a previous study, we identified a conserved cluster of Kruppel-associated box (KRAB)-containing ZNF genes located near the XRCC1 gene in human chromosome 19q13.2 and mouse chromosome 7 and analyzed two members of the murine gene family, Zfp93 and Zfp94, in detail. Here we report the identification and characterization of putative human orthologs of these murine genes. The human genes ZFP93 and ZNF45 are substantially similar to their murine counterparts in overall structure, but two notable differences exist between the sets of genes. First, the human genes encode more ZNF repeats than their murine counterparts. Second, the ZNF repeats that are common to orthologs exhibit varying degrees of conservation. Expression studies indicate that the human genes, like their mouse equivalents, are expressed widely and are coexpressed at similar levels in most adult tissues. These comparative gene sequence and expression studies therefore suggest that at least two members of the mammalian XRCC1-linked KRAB-ZNF gene family were elaborated prior to the divergence of primate and rodent lineages and were well conserved in human and mouse.
遗传图谱和物理图谱研究表明，数百个含锌指（ZNF）的基因分布于人类基因组中，且其中许多基因以家族簇的形式排列。然而，这些串联排列的家族在哺乳动物物种间的保守程度在很大程度上尚不清楚。在之前的一项研究中，我们在人类19号染色体q13.2区域和小鼠7号染色体上靠近XRCC1基因的位置鉴定出了一个保守的含Kruppel相关盒（KRAB）的ZNF基因簇，并详细分析了该小鼠基因家族的两个成员Zfp93和Zfp94。在此，我们报告这些小鼠基因假定的人类直系同源基因的鉴定和特征。人类基因ZFP93和ZNF45在整体结构上与其小鼠对应基因高度相似，但两组基因之间存在两个显著差异。首先，人类基因编码的ZNF重复序列比其小鼠对应基因更多。其次，直系同源基因共有的ZNF重复序列表现出不同程度的保守性。表达研究表明，人类基因与其小鼠对应基因一样，广泛表达且在大多数成年组织中以相似水平共表达。因此，这些比较基因序列和表达研究表明，至少两个与哺乳动物XRCC1相关的KRAB-ZNF基因家族成员在灵长类和啮齿类谱系分化之前就已形成，并且在人类和小鼠中高度保守。
