Polygenic and single-locus selection on BMI during Polynesian expansion.

Area of Science:

• Human evolutionary genetics
• Population genetics
• Metabolic disease research

Background:

• The 'thrifty' variant hypothesis suggests genetic adaptations for energy storage contribute to modern obesity.
• Understanding the timing and population-specific effects of these variants on body mass index (BMI) is crucial.

Purpose of the Study:

• To investigate the evolutionary history and impact of the CREBRF rs373863828-A variant in the Tongan population.
• To explore the role of polygenic adaptation in BMI changes over time in ancestral Tongans.

Main Methods:

• Whole-genome sequencing of 22 Tongan individuals.
• Analysis of allele frequency trajectories using the CLUES program.
• Examination of polygenic selection signals using polarized trait integrated haplotype scores.

Main Results:

• Replicated positive selection signal for the CREBRF rs373863828-A variant in Tongans, indicating broader Polynesian adaptive pressures.
• Inferred a significant increase in the rs373863828-A allele frequency over the last ~100 generations, coinciding with Polynesian maritime expansion.
• Observed an initial increase in BMI polygenic scores followed by a recent decline, with evidence of selection favoring lower BMI in recent generations.

Conclusions:

• The CREBRF variant was strongly selected during oceanic dispersal, aiding adaptation to food-limited environments.
• Multiple modest-effect variants also contributed to adaptation during long sea voyages.
• Recent selection pressures may be shifting towards lower BMI, highlighting a potential evolutionary mismatch with modern environments.