加州大学Megan Y. Dennis小组的研究发现人类特有的基因扩展有助于大脑进化。2025年7月21日出版的《细胞》发表了这项成果。
课题组研究人员构建了一个完整的端粒到端粒基因组序列，以鉴定213个人类特异性基因家族。由此，在所有经过测试的现代人类基因组和大脑转录组中发现了362个类似物，使它们成为人类普遍大脑特征的首选候选者。选择一个类似性的子集，对数百名现代人的长读DNA测序揭示了以前隐藏的选择特征，包括T细胞标记CD8B。
为了了解在大脑发育中的作用，该课题组建立了9个同源基因的斑马鱼CRISPR“敲除”模型，并引入了mRNA编码的类似物，有效地“人源化”了幼虫。他们的发现暗示了两个基因可能对人类大脑的标志性特征有贡献：GPR89B与剂量介导的大脑扩张有关，FRMPD2B与突触信号改变有关。他们的整体方法为研究人类大脑进化的基因扩展驱动因素提供了见解和全面的抵抗。
据介绍，人类谱系中扩增的重复基因可能促进了大脑的进化，但由于序列组装错误，在发现这些基因方面存在挑战。
附：英文原文
Title: Human-specific gene expansions contribute to brain evolution
Author: Daniela C. Soto, José M. Uribe-Salazar, Gulhan Kaya, Ricardo Valdarrago, Aarthi Sekar, Nicholas K. Haghani, Keiko Hino, Gabriana La, Natasha Ann F. Mariano, Cole Ingamells, Aidan Baraban, Zoeb Jamal, Tychele N. Turner, Eric D. Green, Sergi Simó, Gerald Quon, Aida M. Andrés, Megan Y. Dennis
Issue&Volume: 2025-07-21
Abstract: Duplicated genes expanded in the human lineage likely contributed to brain evolution, yet challenges exist in their discovery due to sequence-assembly errors. We used a complete telomere-to-telomere genome sequence to identify 213 human-specific gene families. From these, 362 paralogs were found in all modern human genomes tested and brain transcriptomes, making them top candidates contributing to human-universal brain features. Choosing a subset of paralogs, long-read DNA sequencing of hundreds of modern humans revealed previously hidden signatures of selection, including for T cell marker CD8B. To understand roles in brain development, we generated zebrafish CRISPR “knockout” models of nine orthologs and introduced mRNA-encoding paralogs, effectively “humanizing” larvae. Our findings implicate two genes in possibly contributing to hallmark features of the human brain: GPR89B in dosage-mediated brain expansion and FRMPD2B in altered synapse signaling. Our holistic approach provides insights and a comprehensive resource for studying gene expansion drivers of human brain evolution.
DOI: 10.1016/j.cell.2025.06.037
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00739-1