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PolyQ length-based molecular encoding of vocalization frequency in FOXP2.

Serena Vaglietti1, Veronica Villeri1, Marco Dell'Oca1

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The FOXP2 protein

Keywords:
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Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Genetics

Background:

  • The FOXP2 gene is crucial for vocalization and speech.
  • FOXP2 contains variable polyQ repeat regions (Q1 and Q2) across mammals.
  • The functional significance of FOXP2 polyQ length variation remains unclear.

Purpose of the Study:

  • To investigate the relationship between FOXP2 polyQ length variation and vocalization frequencies.
  • To explore the molecular mechanisms underlying this relationship.
  • To examine patterns of convergent evolution in FOXP2 and FOXP1.

Main Methods:

  • Comparative evolutionary analysis of FOXP2 and FOXP1 polyQ lengths across mammalian species.
  • Molecular studies on FOXP2 polyQ tract structure, condensate formation, and liquid-liquid phase separation (LLPS).
  • Integration of evolutionary and molecular data to link polyQ length to vocalization frequency.

Main Results:

  • The ratio of FOXP2 Q1/Q2 lengths quantitatively correlates with vocalization frequency ranges (infrasonic to ultrasonic).
  • Convergent evolution in polyQ length ratios was observed in species with similar vocalization frequencies (e.g., bats and ultrasonic species).
  • FOXP2 polyQ tracts form molecular condensates and drive LLPS, with length variation impacting structure, LLPS, and transcriptional activity.

Conclusions:

  • PolyQ length variation in FOXP2 acts as a molecular code for vocalization frequency.
  • This provides a novel mechanism linking genotype to acoustic phenotype through protein structure and LLPS.
  • Convergent evolution highlights the adaptive significance of FOXP2 polyQ length regulation in vocal communication.