A LINE-1 insertion upstream of FOXP2 promotes neuronal differentiation during primate evolution

Area of Science:

• Evolutionary genomics
• Neuroscience
• Molecular biology

Background:

• FOXP2 is vital for language and cognition, but its evolutionary path is unclear.
• Long interspersed element-1 (LINE-1) retrotransposons influence genome regulation and development.
• LINE-1's role in shaping FOXP2's regulatory elements is unknown.

Purpose of the Study:

• Investigate the evolutionary role of LINE-1 in the FOXP2 regulatory landscape.
• Understand how LINE-1 insertions impact FOXP2 function and primate brain evolution.

Main Methods:

• Comparative evolutionary genomic analyses.
• Integrative 3D genome mapping in human and marmoset neural stem cells.
• Analysis of LINE-1 retrotransposition events.

Main Results:

• Identified a 10.6 kb composite LINE-1 element (FOXP2-342L1) upstream of FOXP2, present in humans and chimpanzees.
• FOXP2-342L1 mediates long-range chromatin interactions and shows signs of positive selection in humans.
• This element acts as an evolutionary hub for LINE-1 insertions, regulating FOXP2 and promoting cortical neuron differentiation.

Conclusions:

• LINE-1 retrotransposons reconfigured the 3D chromatin architecture of the FOXP2 regulatory landscape.
• Discovered a primate-specific model of neuronal development influenced by LINE-1 activity during primate evolution.