A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe

The suite of adaptations associated with the extreme stature of the giraffe has long interested biologists and physiologists. By generating a high-quality chromosome-level giraffe genome and a comprehensive comparison with other ruminant genomes, we identified a robust catalog of giraffe-specific mutations. These are primarily related to cardiovascular, bone growth, vision, hearing, and circadian functions. Among them, the giraffe FGFRL1 gene is an outlier with seven unique amino acid substitutions not found in any other ruminant. Gene-edited mice with the giraffe-type FGFRL1 show exceptional hypertension resistance and higher bone mineral density, both of which are tightly connected with giraffe adaptations to high stature. Our results facilitate a deeper understanding of the molecular mechanism underpinning distinct giraffe traits, and may provide insights into the study of hypertension in humans.

Automated summary

The suite of adaptations associated with the extreme stature of giraffes is mainly related to cardiovascular, bone growth, vision, hearing, and circadian functions. The giraffe FGFRL1 gene plays a key role in resistance to hypertension and increased bone mineral density, contributing to giraffe's adaptations to their tall stature.