Transcriptional Enhancers in the FOXP2 Locus Underwent Accelerated Evolution in the Human Lineage

Area of Science:

• Evolutionary biology
• Neuroscience
• Genetics

Background:

• Complex human traits like language arise from molecular evolutionary changes in brain development.
• The human-specific evolution of the FOXP2 gene's coding region is associated with speech and language emergence.
• Regulation of FOXP2 expression and its evolutionary trajectory in humans remain largely uncharacterized.

Purpose of the Study:

• To identify human-specific regulatory regions of the FOXP2 gene.
• To investigate the evolutionary changes in FOXP2 regulatory machinery within the human lineage.

Main Methods:

• Utilized databases of human-accelerated noncoding sequences (HARs) to find FOXP2 regulatory regions with human-specific changes.
• Performed in vivo enhancer assays in zebrafish to test the function of identified FOXP2-HARs.
• Compared reporter gene expression from human and chimpanzee FOXP2-HAR sequences in the nervous system.

Main Results:

• The FOXP2 locus is situated within a topologically associating domain containing clusters of HARs, indicating rapid evolutionary acceleration.
• At least five FOXP2-HARs function as transcriptional enhancers during zebrafish development.
• Two FOXP2-HARs direct reporter gene expression to FOXP2-expressing cells, and two show enhanced expression in the nervous system compared to chimpanzee sequences.

Conclusions:

• Regulatory sequences within the FOXP2 locus have undergone human-specific evolution.
• These findings suggest that the transcriptional machinery controlling FOXP2 may have evolved differentially in the human lineage, potentially contributing to language development.