Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517507, Andhra Pradesh, India.
Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati 517507, Andhra Pradesh, India.
Cell Rep. 2023 Jul 25;42(7):112811. doi: 10.1016/j.celrep.2023.112811. Epub 2023 Jul 13.
Protein products of essential genes, indispensable for organismal survival, are highly conserved and bring about fundamental functions. Interestingly, proteins that contain amino acid homorepeats that tend to evolve rapidly are enriched in eukaryotic essentialomes. Why are proteins with hypermutable homorepeats enriched in conserved and functionally vital essential proteins? We solve this functional versus evolutionary paradox by demonstrating that human essential proteins with homorepeats bring about crosstalk across biological processes through high interactability and have distinct regulatory functions affecting expansive global regulation. Importantly, essential proteins with homorepeats rapidly diverge with the amino acid substitutions frequently affecting functional sites, likely facilitating rapid adaptability. Strikingly, essential proteins with homorepeats influence human-specific embryonic and brain development, implying that the presence of homorepeats could contribute to the emergence of human-specific processes. Thus, we propose that homorepeat-containing essential proteins affecting species-specific traits can be potential intervention targets across pathologies, including cancers and neurological disorders.
必需基因的蛋白质产物是生物体生存所必需的，高度保守，具有基本功能。有趣的是，含有易于快速进化的氨基酸同源重复的蛋白质在真核必需组中富集。为什么富含高突变同源重复的蛋白质在保守和功能重要的必需蛋白质中富集？我们通过证明具有同源重复的人类必需蛋白质通过高互作性在生物过程中进行串扰，并具有独特的调节功能来影响广泛的全局调节，从而解决了这个功能与进化的悖论。重要的是，具有同源重复的必需蛋白质会随着氨基酸取代的快速进化而快速进化，这些取代经常影响功能位点，可能促进快速适应。引人注目的是，具有同源重复的必需蛋白质会影响人类特有的胚胎和大脑发育，这意味着同源重复的存在可能有助于人类特有的过程的出现。因此，我们提出，影响物种特异性特征的含有同源重复的必需蛋白质可以成为包括癌症和神经紊乱在内的多种疾病的潜在干预靶点。
