Recent evolution of the developing human intestine affects metabolic and barrier functions

作者：Qianhui Yu, Umut Kilik, Stefano Secchia, Lukas Adam, Yu-Hwai Tsai, Christiana Fauci, Jasper Janssens, Charlie J. Childs, Katherine D. Walton, Rubén López-Sandoval, Angeline Wu, Marina Bellavista, Sha Huang, Calen A. Steiner, Yannick Throm, Michael James Boyle, Zhisong He, Joep Beumer, Barbara Treutlein, Craig B. Lowe, Jason R. Spence, J. Gray Camp · 发表于：Science · 年份：2025 · DOI：10.1126/science.adr8628 · 被引用次数：9 · 研究领域：Digestive system and related health、Diet and metabolism studies、Growth Hormone and Insulin-like Growth Factors

Diet, microbiota, and other exposures make the intestinal epithelium a nexus for evolutionary change; however, little is known about genomic changes associated with adaptation to a distinctly human environment. In this work, we interrogate the evolution of cell types in the developing human intestine by comparing tissue and organoids from humans, chimpanzees, and mice. We find that recent changes in primates are associated with immune barrier function and lipid and xenobiotic metabolism and that human-specific genetic features affect these functions. Enhancer assays, genetic deletion, and in silico mutagenesis resolve evolutionarily important enhancers of lactase ( LCT ) and insulin-like growth factor binding protein 2 ( IGFBP2 ). Altogether, we identify the developing human intestinal epithelium as a rapidly evolving system and show that great ape organoids provide insight into human biology.