人类特有的基因扩展有助于大脑进化

IF 42.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2025-07-21 DOI:10.1016/j.cell.2025.06.037

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

{"title":"人类特有的基因扩展有助于大脑进化","authors":"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","doi":"10.1016/j.cell.2025.06.037","DOIUrl":null,"url":null,"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.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"31 1","pages":""},"PeriodicalIF":42.5000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Human-specific gene expansions contribute to brain evolution\",\"authors\":\"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\",\"doi\":\"10.1016/j.cell.2025.06.037\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":9656,\"journal\":{\"name\":\"Cell\",\"volume\":\"31 1\",\"pages\":\"\"},\"PeriodicalIF\":42.5000,\"publicationDate\":\"2025-07-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cell.2025.06.037\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2025.06.037","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

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。我们使用完整的端粒到端粒基因组序列来鉴定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。选择一个类人猿的子集，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，我们建立了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。我们的发现暗示了两个基因可能对人类大脑的标志特征有贡献：GPR89B在剂量介导的脑扩张中，FRMPD2B在突触信号改变中。我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资源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Human-specific gene expansions contribute to brain evolution

查看原文本刊更多论文

Human-specific gene expansions contribute to brain evolution

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.