Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA.
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Science. 2021 Feb 19;371(6531). doi: 10.1126/science.abc6405.
Genes with novel cellular functions may evolve through exon shuffling, which can assemble novel protein architectures. Here, we show that DNA transposons provide a recurrent supply of materials to assemble protein-coding genes through exon shuffling. We find that transposase domains have been captured-primarily via alternative splicing-to form fusion proteins at least 94 times independently over the course of ~350 million years of tetrapod evolution. We find an excess of transposase DNA binding domains fused to host regulatory domains, especially the Krüppel-associated box (KRAB) domain, and identify four independently evolved KRAB-transposase fusion proteins repressing gene expression in a sequence-specific fashion. The bat-specific KRABINER fusion protein binds its cognate transposons genome-wide and controls a network of genes and cis-regulatory elements. These results illustrate how a transcription factor and its binding sites can emerge.
具有新细胞功能的基因可能通过外显子改组进化，从而组装出新的蛋白质结构。在这里，我们表明转座子为通过外显子改组组装蛋白质编码基因提供了反复出现的物质供应。我们发现转座酶结构域已经被捕获——主要是通过选择性剪接——在四足动物进化的大约 3.5 亿年中，至少独立地形成了 94 次融合蛋白。我们发现转座酶 DNA 结合结构域与宿主调控结构域（尤其是 KRAB 结构域）融合的情况过多，并且鉴定了四个独立进化的 KRAB-转座酶融合蛋白，它们以序列特异性的方式抑制基因表达。蝙蝠特异性的 KRABINER 融合蛋白在全基因组范围内结合其同源转座子，并控制基因和顺式调控元件的网络。这些结果说明了转录因子及其结合位点是如何出现的。
