Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing^1,2. Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals.

从受精卵开始，人体的所有细胞都在不断地发生突变。不同细胞之间共享的突变意味着共同的祖细胞，因此是谱系追踪的自然发生标记^1,2 。在这里，我们使用 511 激光捕获显微切割的全基因组测序重建了三个成年个体正常组织的广泛系统发育。系统发育同一代中的重建胚胎祖细胞通常对成人身体有不同程度的贡献。这种不对称的程度因个体而异，受精卵的两个重建子细胞之间的比例范围为 60:40 至 93:7。不对称性遍及后代，并且同一个体的组织之间可能存在差异。系统发育解析了组织的空间胚胎模式，揭示了源自最新胚胎细胞的成体结肠上皮中平均有 301 个隐窝的连续斑块，以及大脑发育中的空间效应。利用另外十名男性的数据，我们研究了体细胞和种系之间的发育分裂，结果表明胚胎外对原始生殖细胞的贡献。这项研究表明，尽管达到了相同的最终组织模式，但早期的瓶颈和谱系承诺导致个体内部和个体之间胚胎模式的巨大差异。