Impact of intermittent lead exposure on hominid brain evolution

Gene-environmental interactions shape the evolution of brain architecture and function. Neuro-oncological ventral antigen 1 (NOVA1) is one gene that distinguishes modern humans from extinct hominids. However, the evolutionary pressures that selected the modern NOVA1 allele remain elusive. Here, we show using fossil teeth that several hominids (Australopithecus africanus, Paranthropus robustus, early Homo sp., Gigantopithecus blacki, Pongo sp., Homo neanderthalensis, and Homo sapiens) were consistently exposed to lead over 2 million years, contradicting the idea that lead exposure is solely a modern phenomenon. Moreover, lead exposure on human brain organoids carrying the archaic NOVA1 variant disrupts FOXP2 expression in cortical and thalamic organoids, a gene crucial for the development of human speech and language abilities. Overall, the fossil, cellular, and molecular data support that lead exposure may have contributed to the impact of social and behavioral functioning during evolution, likely affording modern humans a survival advantage.