Eichler E E, Hoffman S M, Adamson A A, Gordon L A, McCready P, Lamerdin J E, Mohrenweiser H W
Human Genome Center, BBRP, L-452, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
Genome Res. 1998 Aug;8(8):791-808. doi: 10.1101/gr.8.8.791.
We investigated the organization, architecture, and evolution of the largest cluster ( approximately 4 Mb) of Krüppel-associated box zinc finger (KRAB-ZNF) genes located in cytogenetic band interval 19p12. A highly integrated physical map ( approximately 700 kb) of overlapping cosmid and BAC clones was developed between genetic STS markers D19S454 and D19S269. Using ZNF91 exon-specific probes to interrogate a detailed EcoRI restriction map of the region, ZNF genes were found to be distributed in a head-to-tail fashion throughout the region with an average density of one ZNF duplicon every 150-180 kb of genomic distance. Sequence analysis of 208,967 bp of this region indicated the presence of two putative ZNF genes: one consisting of a novel member of this gene family (ZNF208) expressed ubiquitously in all tissues examined and the other representing a nonprocessed pseudogene (ZNF209), located 450 kb proximal to ZNF208. Large blocks of ( approximately 25-kb) inverted beta-satellite repeats with a remarkably symmetrical higher order repeat structure were found to bracket the functional ZNF gene. Hybridization analysis using the beta-satellite repeat as a probe indicates that beta-satellite interspersion between ZNF gene cassettes is a general property for 1.5 Mb of the ZNF gene cluster in 19p12. Both molecular clock data as well as a retroposon-mapping molecular fossil approach indicate that this ZNF cluster arose early during primate evolution (approximately 50 million years ago). We propose an evolutionary model in which heteromorphic pericentromeric repeat structures such as the beta satellites have been coopted to accommodate rapid expansion of a large gene family over a short period of evolutionary time. [The sequence data described in this paper have been submitted to GenBank under accession nos. AC003973 and AC004004.]
我们研究了位于细胞遗传学带区间19p12的最大Krüppel相关盒锌指（KRAB-ZNF）基因簇（约4 Mb）的组织、结构和进化。在遗传STS标记D19S454和D19S269之间构建了一个高度整合的重叠黏粒和BAC克隆物理图谱（约700 kb）。使用ZNF91外显子特异性探针检测该区域详细的EcoRI限制性图谱，发现ZNF基因在整个区域以头对尾的方式分布，基因组距离每150 - 180 kb平均有一个ZNF重复子。对该区域208,967 bp的序列分析表明存在两个推定的ZNF基因：一个由该基因家族的一个新成员（ZNF208）组成，在所检测的所有组织中普遍表达，另一个代表一个未加工的假基因（ZNF209），位于ZNF208近端450 kb处。发现大片段（约25 kb）的反向β卫星重复序列具有显著对称的高阶重复结构，将功能性ZNF基因包围。使用β卫星重复序列作为探针的杂交分析表明，ZNF基因盒之间的β卫星散布是19p12中1.5 Mb的ZNF基因簇的一个普遍特征。分子钟数据以及逆转座子映射分子化石方法均表明，这个ZNF簇在灵长类进化早期（约5000万年前）出现。我们提出了一个进化模型，其中诸如β卫星等异态着丝粒周围重复结构已被用于适应一个大基因家族在短时间进化过程中的快速扩张。[本文所述序列数据已提交至GenBank，登录号为AC003973和AC004004。]
