Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA;
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA.
Genome Res. 2023 Aug;33(8):1325-1339. doi: 10.1101/gr.277966.123. Epub 2023 Sep 15.
Cys2-His2 zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by the rapid expansion and contraction of numerous subfamilies across the animal phylogeny. The forces and mechanisms underlying rapid ZNF evolution remain poorly understood, but there is growing evidence that, in tetrapods, the targeting and repression of lineage-specific transposable elements (TEs) plays a critical role in the evolution of the Krüppel-associated box ZNF (KZNF) subfamily. Currently, it is unknown whether this function and coevolutionary relationship is unique to KZNFs or is a broader feature of metazoan ZNFs. Here, we present evidence that genomic conflict with TEs has been a central driver of the diversification of ZNFs in animals. Sampling from 3221 genome assemblies, we show that the copy number of retroelements correlates with that of ZNFs across at least 750 million years of metazoan evolution. Using computational predictions, we show that ZNFs preferentially bind TEs in diverse animal species. We further investigate the largest ZNF subfamily found in cyprinid fish, which is characterized by a conserved sequence we dubbed the fish N-terminal zinc finger-associated (FiNZ) domain. Zebrafish possess approximately 700 FiNZ-ZNFs, many of which are evolving adaptively under positive selection. Like mammalian KZNFs, most zebrafish FiNZ-ZNFs are expressed at the onset of zygotic genome activation, and blocking their translation using morpholinos during early embryogenesis results in derepression of transcriptionally active TEs. Together, these data suggest that ZNF diversification has been intimately connected to TE expansion throughout animal evolution.
Cys2-His2 锌指基因（ZNFs）构成后生动物中转录因子最大的家族。ZNF 的进化具有高度动态性，其特征是在动物系统发育过程中，许多亚家族的快速扩张和收缩。快速 ZNF 进化的驱动力和机制仍知之甚少，但越来越多的证据表明，在四足动物中，谱系特异性转座元件（TEs）的靶向和抑制在 Krüppel 相关盒 ZNF（KZNF）亚家族的进化中起着关键作用。目前，尚不清楚这种功能和协同进化关系是否仅存在于 KZNFs 中，还是后生动物 ZNFs 的更普遍特征。在这里，我们提供的证据表明，与 TEs 的基因组冲突一直是动物中 ZNF 多样化的核心驱动力。从 3221 个基因组组装中采样，我们表明，反转录元件的拷贝数与至少 7.5 亿年的后生动物进化过程中的 ZNF 数量相关。通过计算预测，我们表明 ZNF 优先在不同的动物物种中结合 TEs。我们进一步研究了在鲤科鱼类中发现的最大的 ZNF 亚家族，该亚家族的特征是存在一个保守序列，我们将其命名为鱼类 N 端锌指相关（FiNZ）结构域。斑马鱼拥有大约 700 个 FiNZ-ZNF，其中许多在正选择下适应性进化。与哺乳动物 KZNFs 一样，大多数斑马鱼 FiNZ-ZNFs 在合子基因组激活开始时表达，并且在早期胚胎发生期间使用 morpholinos 阻断其翻译会导致转录活性 TEs 的去抑制。总之，这些数据表明，ZNF 的多样化与整个动物进化过程中 TE 的扩张密切相关。
