TY - JOUR T1 - <em>DLX5/6</em> GABAergic expression affects social vocalization: implications for human evolution JF - bioRxiv DO - 10.1101/2020.07.24.218065 SP - 2020.07.24.218065 AU - Giovanni Levi AU - Camille de Lombares AU - Cristina Giuliani AU - Vincenzo Iannuzzi AU - Rym Aouci AU - Paolo Garagnani AU - Claudio Franceschi AU - Dominique Grimaud-Hervé AU - Nicolas Narboux-Nême Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/02/07/2020.07.24.218065.abstract N2 - DLX5 and DLX6 are two closely related transcription factors involved in brain development and in GABAergic differentiation. The DLX5/6 locus is regulated by FoxP2, a gene involved in language evolution and has been associated to neurodevelopmental disorders and mental retardation. Targeted inactivation of Dlx5/6 in mouse GABAergic neurons (Dlx5/6VgatCre mice) results in behavioural and metabolic phenotypes notably increasing lifespan by 33%.Here, we show that Dlx5/6VgatCre mice present a hyper-vocalization and hyper-socialization phenotype. While only 7% of control mice emitted more than 700 vocalizations/10min, 30% and 56% of heterozygous or homozygous Dlx5/6VgatCre mice emitted more than 700 and up to 1400 calls/10min with a higher proportion of complex and modulated calls. Hyper-vocalizing animals were more sociable: the time spent in dynamic interactions with an unknown visitor was more than doubled compared to low-vocalizing individuals.The characters affected by Dlx5/6 in the mouse (sociability, vocalization, skull and brain shape…) overlap those affected in the “domestication syndrome”. We therefore explored the possibility that DLX5/6 played a role in human evolution and “self-domestication” comparing DLX5/6 genomic regions from Neanderthal and modern humans. We identify an introgressed Neanderthal haplotype (DLX5/6-N-Haplotype) present in 12.6% of European individuals that covers DLX5/6 coding and regulatory sequences. The DLX5/6-N-Haplotype includes the binding site for GTF2I, a gene associated to Williams-Beuren syndrome, a hyper-sociability and hyper-vocalization neurodevelopmental disorder. The DLX5/6-N-Haplotype is significantly underrepresented in semi-supercentenarians (&gt;105y of age), a well-established human model of healthy ageing and longevity, suggesting their involvement in the co-evolution of longevity, sociability and speech.Competing Interest StatementThe authors have declared no competing interest. ER -