A recent evolutionary change affects a regulatory element in the human FOXP2 gene

Area of Science:

• Genetics
• Evolutionary Biology
• Paleoanthropology

Background:

• The FOXP2 gene plays a critical role in the normal development of human speech and language.
• Understanding genetic changes in FOXP2 is key to tracing human evolutionary history and the development of complex communication.

Purpose of the Study:

• To investigate genetic variations in the FOXP2 gene between modern humans and Neandertals.
• To identify potential functional consequences of these variations on gene regulation and evolutionary selection.

Main Methods:

• Isolation and sequencing of FOXP2 genomic DNA from a 49,000-year-old Neandertal and 50 present-day humans.
• Analysis of specific substitutions, particularly in intron 8, affecting transcription factor binding sites.
• Reporter construct assays to assess the functional impact of identified alleles on transcriptional activity.

Main Results:

• Identified substitutions in FOXP2 present in modern humans but absent or variable in Neandertals.
• A substitution in intron 8 alters a binding site for the transcription factor POU3F2.
• The derived allele shows reduced transcriptional activation and altered POU3F2 binding compared to the ancestral allele.

Conclusions:

• The identified substitution in the POU3F2 binding site likely modifies FOXP2 gene regulation.
• This variation, located in a region under positive selection, is a strong candidate for a recent selective sweep in the human FOXP2 gene.
• These findings provide insights into the genetic underpinnings of human language evolution.