Differential gene expressions in the mice with Neanderthal/Denisovan-type GLI3 variant

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 created the mice with corresponding amino acid change (R1540C) in Gli3 and performed RNA-seq analyses.