Modeling recent human evolution in mice by expression of a selected EDAR variant

Area of Science:

• Human evolutionary genetics
• Mammalian developmental biology
• Population genetics

Background:

• The EDARV370A allele is a strong candidate for recent positive selection in the human genome.
• Its precise biological significance and adaptive role remain incompletely understood.
• Previous associations include altered hair and tooth morphology.

Purpose of the Study:

• To investigate the biological significance and adaptive role of the EDARV370A variant.
• To characterize the phenotype of EDARV370A in a mouse model.
• To explore the evolutionary origins and human population associations of EDARV370A.

Main Methods:

• Computational analysis of allele origin and timing.
• Generation of a knockin mouse model for EDARV370A.
• Phenotypic characterization in mice and association studies in Han Chinese populations.

Main Results:

• The EDARV370A allele likely originated in central China ~30,000 years ago.
• EDARV370A mice exhibit increased hair thickness, mirroring human phenotypes.
• The mutation affects mammary and eccrine glands, with increased active eccrine glands observed in Han Chinese individuals.

Conclusions:

• EDARV370A represents a significant adaptive genetic variation in humans.
• The variant influences hair, mammary, and eccrine gland development and function.
• This research provides interdisciplinary insights into human adaptive evolution.