Our ancestors acquired morphological, cognitive and metabolic modifications that enabled humans to colonize diverse habitats, develop extraordinary technologies and reshape the biosphere. Understanding the genetic, developmental and molecular bases for these changes will provide insights into how we became human. Connecting human-specific genetic changes to species differences has been challenging owing to an abundance of low-effect size genetic changes, limited descriptions of phenotypic differences across development at the level of cell types and lack of experimental models. Emerging approaches for single-cell sequencing, genetic manipulation and stem cell culture now support descriptive and functional studies in defined cell types with a human or ape genetic background. In this Review, we describe how the sequencing of genomes from modern and archaic hominins, great apes and other primates is revealing human-specific genetic changes and how new molecular and cellular approaches — including cell atlases and organoids — are enabling exploration of the candidate causal factors that underlie human-specific traits.

我们的祖先获得了形态、认知和代谢方面的改变，使人类能够殖民不同的栖息地，开发非凡的技术并重塑生物圈。了解这些变化的遗传、发育和分子基础将为我们如何成为人类提供见解。由于大量低效应大小的遗传变化、细胞类型水平上发育过程中表型差异的描述有限以及缺乏实验模型，将人类特异性遗传变化与物种差异联系起来一直具有挑战性。单细胞测序、基因操作和干细胞培养的新兴方法现在支持对具有人类或猿遗传背景的特定细胞类型进行描述性和功能性研究。在这篇综述中，我们描述了现代和古代人类、类人猿和其他灵长类动物的基因组测序如何揭示人类特有的遗传变化，以及新的分子和细胞方法——包括细胞图谱和类​​器官——如何能够探索候选因果关系。构成人类特定特征的因素。