The Gene Regulatory Evolution of the Human Skeleton (Massively parallel reporter assay (MPRA))

Changes in gene regulation are key drivers of human evolution. However, which regulatory changes shaped human adaptations, and especially how, remains largely unknown.

Skeletal alterations have been particularly central in human evolution, facilitating upright locomotion and large brains, and influencing child- birth and our distinctive faces. Here, we employed MPRAs in key skeletal cells - chondrocytes - to uncover the functional role of the 574,290 enhancer and promoter substitutions that distinguish humans from their ape relatives. Using this atlas, we identified 15,077 sequences whose activity has diverged since our split from chimpanzees.