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

In a study published in PNAS on September 2, a research team led by Ming-Shan Wang at the Kunming Institute of Zoology, Chinese Academy of Sciences, integrated single-nucleus RNA sequencing (snRNA-seq), population genomics, and machine learning to investigate how domestication influences hippocampal cell composition, regulation, and evolution.

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. The researchers first generated a high-resolution single-cell transcriptomic atlas of the chicken hippocampus. Comparative analyses across vertebrate species revealed that the major cellular components of the hippocampus were established in the common ancestor of amniotes and were subsequently reshaped during avian evolution.

The researchers also identified neural progenitor cells (NPCs) in the adult chicken hippocampus, including neuronal precursors (Pre) and intermediate progenitor cells (IPCs; IPC1 and IPC2), cell populations that play important roles in adult neurogenesis in mammals. Further transcriptomic analyses and experimental validation supported the presence of these progenitor populations and their differentiation trajectories. Together with observations from other avian species, these findings suggest that adult hippocampal neurogenesis may be more broadly conserved across birds than previously appreciated.

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

Together, these findings provide cellular and evolutionary insights into how domestication may have reshaped hippocampal neurogenic programs. The results support a model in which changes in neural progenitor populations and their regulatory programs may contribute to altered stress and fear responses, potentially facilitating behavioral adaptation to human-managed environments.

Figure 1: Evidence for hippocampal neurogenesis in adult birds.

Figure 2: FKBP5 expression is associated with stress response.

Contact:

Hu LiRong, WANG MingShan

Kunming Institute of Zoology, Chinese Academy of Sciences,

Kunming, Yunnan 650201, China

E-mail: wangmingshan@mail.kiz.ac.cn (MSW)