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 evolutive pressures that selected the modern NOVA1 allele remain elusive. Here, we show that fossil teeth from several hominids (Australopithecus africanus, Paranthropus robustus, early Homo sp., Gigantopithecus blacki, Pongo sp., Papio sp., Homo neanderthalensis, and Homo sapiens) were consistently exposed to lead over two million years, contradicting the idea that lead exposure is solely a modern phenomenon. Moreover, lead exposure on brain organoids carrying the archaic NOVA1 variant suppresses FOXP2 expression in cortical neurons. Overall, the fossil, cellular, and molecular data support that lead exposure impacted social and behavioral functioning during evolution, likely affording modern humans a survival advantage.