At the origin of Neanderthals and modern humans - Cerebral complexity and encephalization

The increase of brain dimensions and complexity has characterized the evolution of the genus Homo. According to the available fossil and genetic evidence, a crucial stage came before the divergence of Neanderthals, Denisovans and Homo sapiens, during the Middle Pleistocene. We consider a specimen of about 400 ka, whose phenotype is at the roots of this divergence: Ceprano calvarium (Italy). Here, we show a derived cerebrovascular organization with a mosaic of modern human and primitive features characteristics. Computed microtomography shows vascular variation and ontogenetic defects associated with ventricular and lymphatic involvement while phylogenetic analyzes highlight a dysregulation of the Tet1 gene that shows an accelerated mutation rate between 1.2 Ma and 466 ka, in contrast with the expected neutral evolution of the human genome. These results shed light on the dynamics of cranio-cerebral growth during the encephalization process and on the cerebral vascular and lymphatic system involved in this process. The results of this study could have implications for the research of many of the diseases of the central nervous system that have become predominant in an increasingly structured and long-lived brain system such as that of modern Homo sapiens. One-Sentence Summary: Genetic mutation, anatomical variations and glymphatic system in the process of encephalization towards Homo sapiens.