Hamilton Aaron T, Huntley Stuart, Tran-Gyamfi Mary, Baggott Daniel M, Gordon Laurie, Stubbs Lisa
Genome Biology Division, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
Genome Res. 2006 May;16(5):584-94. doi: 10.1101/gr.4843906. Epub 2006 Apr 10.
Most genes are conserved in mammals, but certain gene families have acquired large numbers of lineage-specific loci through repeated rounds of gene duplication, divergence, and loss that have continued in each mammalian group. One such family encodes KRAB-zinc finger (KRAB-ZNF) proteins, which function as transcriptional repressors. One particular subfamily of KRAB-ZNF genes, including ZNF91, has expanded specifically in primates to comprise more than 110 loci in the human genome. Genes of the ZNF91 subfamily reside in large gene clusters near centromeric regions of human chromosomes 19 and 7 with smaller clusters or isolated copies in other locations. Phylogenetic analysis indicates that many of these genes arose before the split between the New and Old World monkeys, but the ZNF91 subfamily has continued to expand and diversify throughout the evolution of apes and humans. Paralogous loci are distinguished by divergence within their zinc finger arrays, indicating selection for proteins with different regulatory targets. In addition, many loci produce multiple alternatively spliced transcripts encoding proteins that may serve separate and perhaps even opposing regulatory roles because of the modular motif structure of KRAB-ZNF genes. The tissue-specific expression patterns and rapid structural divergence of ZNF91 subfamily genes suggest a role in determining gene expression differences between species and the evolution of novel primate traits.
大多数基因在哺乳动物中是保守的,但某些基因家族通过基因重复、分化和丢失的反复循环获得了大量的谱系特异性位点,这些过程在每个哺乳动物群体中持续存在。其中一个家族编码KRAB-锌指(KRAB-ZNF)蛋白,其作为转录抑制因子发挥作用。KRAB-ZNF基因的一个特定亚家族,包括ZNF91,在灵长类动物中特异性扩增,在人类基因组中包含超过110个位点。ZNF91亚家族的基因位于人类染色体19和7着丝粒区域附近的大基因簇中,在其他位置有较小的簇或孤立的拷贝。系统发育分析表明,这些基因中的许多在新大陆猴和旧大陆猴分化之前就已出现,但ZNF91亚家族在猿类和人类的整个进化过程中持续扩增和多样化。旁系同源位点通过其锌指阵列内的差异来区分,这表明对具有不同调控靶点的蛋白质进行了选择。此外,许多位点产生多种可变剪接转录本,编码的蛋白质可能由于KRAB-ZNF基因的模块化基序结构而发挥不同甚至相反的调控作用。ZNF91亚家族基因的组织特异性表达模式和快速的结构分化表明其在决定物种间基因表达差异和新的灵长类性状进化中发挥作用。