Show Notes
Humans live in a world of ideas—born in the brain, shared through language, accumulated in culture across generations, and made reality. Professor Alysson Muotri, UC San Diego Departments of Pediatrics and Cellular and Molecular Medicine, examines how human brain evolution reflects the interplay between genetic innovation and environmental pressures, focusing on Neuro-oncological ventral antigen 1 (NOVA1), an evolutionarily conserved splicing regulator essential for neural development with a protein-coding substitution unique to modern humans compared with Neanderthals and Denisovans. By reintroducing the archaic NOVA1 allele into human induced pluripotent stem cells and studying cortical organoids, the work finds accelerated maturation, increased surface complexity, altered synaptic marker expression, and changes in electrophysiological properties. Muotri also analyzes long-term lead exposure using fossilized teeth from multiple hominid species spanning over two million years, revealing pervasive exposure across extinct and extant hominids. Lead exposure selectively disrupted FOXP2 expression in cortical and thalamic organoids carrying the archaic NOVA1 variant, and findings were independently validated in NOVA1 humanized mouse models with altered vocalization. Together, these results suggest gene–environment interactions may have influenced neural circuit development, social behavior, and complex language capacity. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 41297]
More from CARTA - Anthropogeny (Audio)
Ajit Varki, Distinguished Professor in the Departments of Medicine and Cellular & Molecular Medicine, Co-Director of CARTA, and Co-Director of the Glycobiology Research and Training Center at the University of California, San Diego, focuses on a family of cell surface sugars called the sialic acids, and their roles in biology, evolution and disease. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 21987]
Genevieve Konopka is an Assistant Professor of Neuroscience at UT Southwestern Medical Center. The focus of her research is elucidating how developmental signaling pathways are disrupted in neuropsychiatric illnesses, and identifying human-specific pathways that are vulnerable to neuropsychiatric disease. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 21986]
Yoav Gilad is Associate Professor of Human Genetics at the University of Chicago. He studies genetic and regulatory differences between humans and our close evolutionary relatives, with the long-term goal of identifying the genetic basis for human-specific traits, including genetic variation that underlies higher susceptibility to certain diseases and disorders in humans than in other primates. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 21985]
Katherine Pollard, Associate Investigator at the Gladstone Institutes and Associate Professor of Biostatistics at UC San Francisco, specializes in evolutionary genomics, in particular identifying genome sequences that differ significantly between or within species and their relationship to biomedical traits. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 21984]
Alysson Muotri, Assistant Professor at UC San Diego, focuses on human brain development and evolution, exploring mobile elements as generators of neuronal diversity. He is also interested in modeling neurological diseases using human induced pluripotent stem cells. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 21983]