KRAB型锌指蛋白的进化及在物种演化中的功能

Evolution of KRAB-containing zinc finger proteins and their roles in species evolution

C2H2型锌指蛋白家族是目前发现的哺乳动物中最大的转录/转录调控因子家族,由一小群古老的含有真核锌指结构的转录因子经过多次基因复制和功能分化演化而来。KRAB型锌指蛋白(KRAB.containing zinc finger proteins,KRAB-ZFPs)作为C2H2型锌指蛋白家族中最大的亚家族,最早出现在四足脊椎动物,并随物种的进化数量快速增长,在人类中占据C2H2型锌指蛋白的60%左右。在物种演化中,进化压力主要改变KRAB-ZFPs的DNA结合能力,而KRAB-ZFPs介导的转录抑制能力则稳定存在。同时,多种KRAB-ZFPs能够与KRAB相关蛋白1(KRAB-associated protein 1,KAP1)协同作用沉默哺乳动物中反转录元件的活性,并与之协同进化,严格限制反转录原件的跳跃能力。本文综述了KRAB-ZFPs的数量倍增、锌指结构的灵活多变、KRAB-ZFPs/KAP1的转录抑制能力和反转录元件的跳跃性在促进哺乳动物调控网络的差异、基因组稳定性的变化和物种进化中的作用,旨在进一步揭示KRAB-ZFPs在推动物种稳定演化中的特点和功能。

The C2H2 zinc finger protein family,one of the largest families of transcription factor/transcriptional regulator in mammal,arose from a small ancestral group of eukaryotic zinc finger transcription factors through many repeated gene duplications accompanied by functional divergence.As the biggest subfamily of C2H2 zinc finger protein family,Kruppel-associated box-containing zinc finger proteins（KRAB-ZFPs） appeared at the period oftetrapod,expand rapidly along with species evolution,and take about 60%of the total C2H2 zinc finger proteins in human.During species evolution,the DNA binding ability of KRAB-ZFPs is changed while the KRAB-ZFPs-mediate transcriptional repression ability maintains stable under the evolution pressure.Moreover,multiple KRAB-ZFPs function synergistically with KAP1 on transcriptional silencing of retroelements,and the coevolution between KRAB-ZFPs and target retrotransposons restrict the jumping ability of the retroelements.In this review,we summarize the roles of KRAB-ZFPs duplication,the flexibility of zinc finger structure,transcriptional repression of KRAB-ZFPs/KAP1 and retroelement ＂jump＂ in promoting the divergence in regulatory network,stable genome change and species evolution,in order to reveal the characters and functions of KRAB-ZFPs in driving species evolution stably.