2026年6月10日，牛津大学Sebastian M. Shimeld团队在《自然》杂志发表论文，宣布他们的最新研究探明了全基因组复制塑造了脊椎动物大脑的细胞型进化。

为了探究同源物是否在这一过程中起着重要的机制作用，研究小组预测了祖先细胞的类型状态，并将它们与文昌鱼进行了比较，并对大胶质细胞进行了实验研究。研究结果表明，同源物在早期脊椎动物细胞类型多样化中起着重要作用。

此外，通过检查细胞类型和物种间的平行表达，该研究团队发现表达变化主要由剂量选择和亚功能化驱动。小组还将同源物与不同解剖和细胞类型尺度上的细胞多样性联系起来。他们的发现证明了WGDs对早期脊椎动物大脑复杂性进化的重要性，并强调了由此产生的同源物在形成后很长一段时间内继续促进细胞型进化。

据介绍，脊椎动物复杂的大脑比它们的近亲有更多的细胞类型。全基因组复制（WGDs）发生在脊椎动物的早期进化过程中，但目前尚不清楚这些复制的基因（同源基因）是否促进了细胞类型的进化。本文对五种脊索动物（人类、小鼠、蜥蜴、七鳃鳗和文昌鱼）的大脑单细胞转录组进行了主题化，发现脊椎动物中许多具有保守核心转录因子的细胞类型家族与文昌鱼没有一一同源性。此外，同源物，特别是来自第一个WGD的同源物，在脊椎动物细胞型进化中比小规模复制同源物更重要。

附：英文原文

Title: Whole-genome duplication shaped cell-type evolution in the vertebrate brain

Author: Zhu, Yuanzhen, Zhang, Shuai, Wei, Jiankai, Dolgetta-Garcia, Diego, Jindrich, Katia, Liu, Huimin, Shi, Chenggang, Pan, Rongrong, Chen, Yuwei, Xu, Yan, Li, Qiye, Wagner, Gnter P., Holland, Peter W. H., Li, Guang, Shimeld, Sebastian M.

Issue&Volume: 2026-06-10

Abstract: The complex brains of vertebrates have more cell types than those of their closest relatives. Whole-genome duplications (WGDs) occurred during early vertebrate evolution1, but it is unclear whether the duplicated genes (ohnologues) facilitated cell-type evolution. Here using brain single-cell transcriptomes from five chordates—human2, mouse3, lizard4, lamprey5 and amphioxus—we report that many cell-type families with conserved core transcription factors in vertebrates do not show one-to-one homology with amphioxus. Moreover, ohnologues, particularly those from the first WGD, were more important than small-scale duplication paralogues for vertebrate cell-type evolution. To explore whether ohnologues are mechanistically important for this process, we predicted ancestral cell-type states and compared them to amphioxus and experimentally investigated macroglia. The findings indicate that ohnologues had a role in early vertebrate cell-type diversification. Moreover, by examining paralogue expression across cell types and species, we show that expression changes were mainly driven by dosage selection and subfunctionalization. We also link ohnologues to cellular diversity at different anatomical and cell-type scales. Our findings demonstrate the importance of WGDs for the evolution of early vertebrate brain complexity and highlight that the resultant ohnologues continued to capacitate cell-type evolution long after they were formed.

DOI: 10.1038/s41586-026-10629-x

Source: https://www.nature.com/articles/s41586-026-10629-x