Dosage analysis of the 7q11.23 Williams region identifies as a major human gene patterning the modern human face and underlying self-domestication.

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Zanella, Matteo; Vitriolo, Alessandro; Andirko, Alejandro; Martins, Pedro Tiago; Sturm, Stefanie; O'Rourke, Thomas; Laugsch, Magdalena; Malerba, Natascia; Skaros, Adrianos; Trattaro, Sebastiano; Germain, Pierre-Luc; Mihailovic, Marija; Merla, Giuseppe; Rada-Iglesias, Alvaro; Boeckx, Cedric; Testa, Giuseppe
Year of Publication: 2019
Journal: Sci Adv
Volume: 5
Issue: 12
Pagination: eaaw7908
Date Published: 2019 12
Publication Language: eng
ISSN: 2375-2548

We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest (NC) stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 copy number variants. Our results reveal a key contribution of BAZ1B to NCSC in vitro induction and migration, coupled with a crucial involvement in NC-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we found a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the human self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face. In so doing, we provide experimental evidence that the craniofacial and cognitive/behavioral phenotypes caused by alterations of the Williams-Beuren syndrome critical region can serve as a powerful entry point into the evolution of the modern human face and prosociality.

DOI: 10.1126/sciadv.aaw7908
Alternate Journal: Sci Adv