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

Area of Science:

• Evolutionary biology
• Genomics
• Human biology

Background:

• The intestinal epithelium is a key site for evolutionary adaptation due to diet and microbial interactions.
• Genomic changes driving adaptation to human-specific environments remain largely unknown.

Purpose of the Study:

• To investigate the evolution of cell types in the developing human intestine.
• To identify genomic changes associated with human adaptation.

Main Methods:

• Comparative analysis of developing intestinal tissues and organoids from humans, chimpanzees, and mice.
• Enhancer assays, genetic deletion, and in silico mutagenesis.
• Investigated human-specific genetic features impacting key functions.

Main Results:

• Recent primate evolution shows changes in immune barrier function and lipid/xenobiotic metabolism.
• Human-specific genetic features significantly influence these functions.
• Identified key evolutionary enhancers for lactase (LCT) and IGFBP2.

Conclusions:

• The developing human intestinal epithelium is a rapidly evolving system.
• Great ape organoids offer valuable insights into human biology and evolution.
• Human adaptation involves specific genomic changes affecting gut functions.