Extensive Regulatory Changes in Genes Affecting Vocal and Facial Anatomy Separate Modern Humans from Neanderthals and Denisovans

Changes in gene regulation are broadly accepted as key drivers of phenotypic differences between closely related species. However, identifying regulatory changes that shaped human-specific traits is a very challenging task. Here, we use >60 DNA methylation maps of ancient and present-day human groups, as well as six chimpanzee maps, to detect regulatory changes that emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes affecting vocalization and facial features went through particularly extensive methylation changes. Specifically, we identify silencing patterns in a network of genes (SOX9, ACAN, COL2A1 and NFIX), and propose that they might have played a role in the reshaping of the human face, and in forming the 1:1 vocal tract configuration that is considered optimal for speech. Our results provide insights into the molecular mechanisms that may have shaped the modern human face and voice, and suggest that they arose after the split from Neanderthals and Denisovans.