From Wild to Domestic: Single-cell Transcriptomic Perspectives on Hippocampal Regulation and Evolution

Understanding how domestication reshapes brain structure and function remains a fundamental question in evolutionary biology. The hippocampus is a key brain region involved in memory and stress regulation, and it has been thought to undergo "simplification" during domestication. However, the cellular mechanisms underlying these changes remain poorly understood.

In a study published in PNAS on Sept. 2, a research team led by WANG Mingshan from the Kunming Institute of Zoology of the Chinese Academy of Sciences investigated how domestication influences hippocampal cell composition, regulation, and evolution by integrating single-nucleus RNA sequencing (snRNA-seq), population genomics, and machine learning.

The domestic chicken (Gallus gallus domesticus) and its closest wild relative, the Red Junglefowl (Gallus gallus spadiceus), provide a powerful system for investigating the effects of domestication on the brain. Researchers created a high-resolution single-cell transcriptomic atlas of chicken hippocampus. Comparative analyses across vertebrate species showed that major cellular components of the hippocampus are established in the common ancestor of amniotes and are then reshaped during avian evolution.

Besides, researchers identified neural progenitor cells (NPCs) in adult chicken hippocampus which play important roles in adult neurogenesis in mammals. Transcriptomic analyses and experimental validation supported the presence of these progenitor populations and their differentiation trajectories. This finding, together with observations from other avian species, suggest that adult hippocampal neurogenesis may be more broadly conserved across birds than previously appreciated.

Moreover, researchers revealed that genes associated with NPC states and cell-marker programs show signatures of natural selection, and many of them are involved in the regulation of neurogenesis and pathways related to stress and fear responses. They identified signals of selection near the promoter of FKBP5, a key regulator of the stress response. These genetic changes influence FKBP5 expression in the NPC lineage and contribute to the modulation of stress responses during domestication.

This study provides a cellular and genetic perspective on how domestication reshapes the brain, and offers a basis for further investigation into the mechanisms of neural evolution within the context of microevolution.