Shaping the human brain: evolutionary cis-regulatory plasticity drives changes in synaptic activity-controlled...

Area of Science:

• Neuroscience
• Genetics
• Evolutionary Biology

Background:

• Neuronal activity regulates gene expression crucial for synaptic function and plasticity.
• While core pathways are conserved, species-specific differences exist in gene activity responses.

Purpose of the Study:

• To explore the origins of dissimilarities in activity-regulated transcription between species.
• To investigate the role of cis-regulatory evolution in shaping neuronal gene expression diversity.

Main Methods:

• Comparative analysis of neuronal activity-induced gene expression.
• Focus on synapse-to-nucleus signaling pathways.
• Examination of cis-regulatory elements and transcription factor binding sites.

Main Results:

• Synapse-to-nucleus signaling pathways are evolutionarily conserved.
• Cis-regulatory plasticity has remodeled the enhancer landscape, leading to species-specific gene regulation.
• Evolutionary changes in transcription factor binding sites contribute to diversity.

Conclusions:

• Species-specific differences in activity-regulated transcription arise from cis-regulatory evolution.
• The enhancer landscape's remodeling by cis-regulatory plasticity drives these variations.
• This plasticity may confer unique qualities to human neuronal gene programs.