Transcriptional Interference Regulates the Evolutionary Development of Speech

Area of Science:

• Evolutionary genetics
• Developmental biology
• Primate evolution

Background:

• The genetic basis of human speech evolution remains largely unknown.
• Primate evolutionary development, particularly of the larynx and wrist, is poorly understood.
• A large family presented with speech impairment and retrograde wrist/larynx development.

Purpose of the Study:

• To investigate the evolutionary genetics of speech and its link to primate development.
• To identify the genetic cause of retrograde larynx and wrist development in a human family.
• To elucidate the role of the primate-specific gene TOSPEAK in human evolution.

Main Methods:

• Studied a family with retrograde development of the larynx and wrist.
• Identified a disrupted primate-specific gene, TOSPEAK.
• Utilized transgenic mouse models to analyze TOSPEAK's regulation of GDF6 enhancers.

Main Results:

• Disruption of TOSPEAK caused severe speech impairment and retrograde larynx/wrist development.
• TOSPEAK contains GDF6 enhancers regulating expression in the wrist.
• TOSPEAK evolved a human-specific promoter with increased strength, correlating with speech capacity.

Conclusions:

• TOSPEAK plays a dual role in the evolutionary development of the larynx, wrist, and human speech.
• Transcriptional interference of GDF6 by TOSPEAK is key to hominid evolutionary development.
• Reduced TOSPEAK transcription leads to retrogression of these traits, as seen in the affected family.