Lead poisoning is usually seen as a by-product of industrialization; a consequence of pipes, paint, and petrol. But it may also have influenced the evolution of our genome. In a new study published in Science Advances1, researchers report that lead exposure has been part of primate life for more than two million years.
Fossil teeth from ancient hominids and great apes revealed repeated, biologically incorporated traces of the metal. In laboratory experiments, the team found that lead exposure affected brain organoids carrying an archaic version of neuro-oncological ventral antigen 1 (NOVA1), a gene involved in neural development, altering the expression of FOXP2, a gene known to be key to speech and language. The results suggest that environmental toxins may have acted as evolutionary forces, shaping the genetic networks that underpin cognition and communication.
The researchers combined geochemical and molecular approaches to trace the effects of lead exposure through time. Using laser ablation and mass spectrometry, they measured lead in 51 fossil teeth from species including Australopithecus africanus, Paranthropus robustus, Gigantopithecus blacki, Homo neanderthalensis, and Homo sapiens. 73% of samples contained clear biogenic bands of lead that followed tooth growth lines, showing repeated exposure during life rather than later contamination. These bands were found in specimens up to 2 million years old from sites across Africa, Asia, and Europe. Modern human teeth from the mid-20th century, when leaded fuel and paint were common, showed similar banding patterns, confirming that the signal reflected physiological uptake. The data indicate that intermittent exposure to environmental lead, from natural geological sources such as mineral dust or groundwater, was widespread throughout hominid evolution.
To test whether this exposure could have influenced brain development, the team used induced pluripotent stem cells to create cortical and thalamic brain organoids carrying either the modern (NOVA1hu/hu) or archaic (NOVA1ar/ar) gene variant. Organoids were exposed to low concentrations of lead acetate (10 or 30 µM) for ten days. Lead exposure altered gene expression in both variants, but had stronger effects on organoids with the archaic allele. RNA sequencing and proteomic analysis showed disruption of pathways controlling synapse formation, axon guidance, and cell signaling.
Single-cell analyses also revealed widespread effects on RNA processing. Lead exposure altered alternative splicing in several genes central to thalamic development and synaptic regulation, including TCF7L2, NSD3, and EDNRB. These changes were tightly connected to a broader regulatory network linking NOVA1 with FOXP2, POU3F2, and GRID2, suggesting that NOVA1 may act as a key node coordinating transcriptional and post-transcriptional responses to neurotoxic stress.
Proteomic data supported the transcriptional findings: pathways involving Rho GTPase signalling and ROBO receptor function, essential for axon guidance and thalamocortical connectivity, were significantly disrupted. These effects align with the roles of ROBO1 and related genes in the formation of neural circuits supporting speech and motor control.
In cortical organoids with the NOVA1ar/ar variant, FOXP2 expression fell after low-level lead exposure and rose again at higher concentrations, suggesting an unstable regulatory response. Interestingly, the pattern differed in thalamic organoids: FOXP2 was overexpressed in archaic variant organoids and further increased lead exposure, highlighting tissue-specific vulnerabilities. Because FOXP2 controls neural circuits linked to language and motor learning, its dysregulation points to potential developmental consequences. The modern NOVA1 variant showed greater stability under the same conditions, hinting at increased resilience to environmental neurotoxins.
This study links a long history of environmental lead exposure to the evolution of genes involved in neural development. The experiments suggest that the NOVA1ar/ar variant was less able to maintain stable gene expression when exposed to lead, while the NOVA1hu/hu variant buffered that stress more effectively. These differences may have offered an evolutionary advantage to populations carrying the modern allele.
The study also points to a possible mechanistic link between lead exposure, FOXP2 dysregulation, and neuropsychiatric phenotypes such as those observed in 22q11.2 deletion syndrome. In this context, FOXP2 overexpression in NOVA1ar/ar organoids mirrors findings from thalamocortical organoid models of 22q11.2-associated disorders, highlighting its relevance to both language function and cognitive vulnerability under environmental stress.
The interaction between NOVA1 and FOXP2 connects an environmental toxin with a molecular pathway central to speech and language. If lead exposure repeatedly disrupted neural circuits in early hominids, individuals with more resilient genetic networks may have had a cognitive or behavioral advantage. While the results stop short of proving that lead formed the human lineage, they provide a plausible mechanism for how environmental stress can drive selection on genes linked to brain function.
The findings also add evidence that human evolution involved feedback between changing environments and emerging genetic adaptations. Rather than acting in isolation, genes such as NOVA1 and FOXP2 appear to have evolved within the context of continuous exposure to natural neurotoxins and other environmental pressures that shaped the primate brain.
The authors note several limitations of this study. Brain organoids, while valuable for studying early neurodevelopment, are simplified systems that cannot fully replicate the structure or function of a mature brain. They lack vascularisation, the full diversity of neural and glial cell types, and long-range connectivity, limiting their ability to model later developmental stages or complex behaviours. As a result, the findings should be viewed as initial evidence of gene–environment interaction rather than direct proof of evolutionary causation. The team suggests that complementary in vivo models will be needed to confirm how lead exposure may have shaped neural and cognitive evolution.
The idea that environmental toxins can act as evolutionary forces reframes how we think about both past and present exposures. Lead, once viewed mostly as a modern pollutant, now appears to have been a consistent background factor in primate biology. Its persistence through geological and industrial time connects ancient selective pressures with today’s public health challenges.
The work by Joannes-Boyau and colleagues adds a genomic dimension to this story. It shows that the ability to tolerate neurotoxins may have influenced the evolution of neural genes such as NOVA1 and FOXP2, genes that, in modern humans, are linked to neurodevelopmental disorders and communication. Understanding how these pathways respond to environmental stress could help explain differences in vulnerability to toxins and variation in cognitive traits across populations.
At a broader level, the study highlights the need to view environmental exposure and genetic variation as part of the same system. The same biological pathways that once supported adaptation also underlie modern susceptibility to lead and other neurotoxins. For genomics, this reinforces an old lesson: evolution and environment are tightly connected, and the genetic legacy of ancient exposures still shapes how our brains develop and function today.