Functional analyses of a Neanderthal GLI3 variant GLI3R1537C. Homo sapiens

The evolution of human-specific traits is thought to be tightly coupled with changes in genomic structures. However, phenotypic contributions of lineage-specific genetic variations during human evolution remained elusive. In this project, we focused on a Neanderthal variant of GLI3, a transcription factor that is essential for embryogenesis. All sequenced Neanderthal carry a Arginine to Cysteine substitution in GLI3 C-terminus (R1537C), which corresponding to transcriptional activation domain. To investigate the effect of the substitution on GLI3-dependent downstream gene regulations, we overexpressed modern human type GLI3 and a Neanderthal-type GLI3 into HEK293T cells and performed RNA-seq analyses.