Abstract
The 'thrifty' variant hypothesis, which posits that certain genetic adaptations promoting efficient energy storage during periods of food scarcity, has been invoked to explain the high prevalence of obesity in modern human populations. Although several candidate variants have been proposed, the timing and effects of these variants on body mass index (BMI) in specific populations remain poorly understood. In this study, we performed whole-genome sequencing of 22 Tongan individuals. A previous study identified the rs373863828-A variant in the CREBRF gene as a target of positive selection in Samoans based on iHS analysis. Here, we replicated this signal in Tongans, confirming that this variant has been subject to adaptive pressures more broadly across Polynesian populations. Using the CLUES program, we inferred the allele frequency trajectory of rs373863828-A in Tongans, revealing a marked increase over the past ~100 generations that temporally aligns with the period of Polynesian maritime expansion. The trajectory of the Polygenic Score (PS) showed an increase in the PS for BMI in ancestors of Tongans between 150 and 50 generations ago, followed by a recent decline. Analysis of polarized trait integrated haplotype scores detected significant polygenic selection favoring lower BMI in recent generations. Our findings suggest that the CREBRF variant underwent strong positive selection during oceanic dispersal, while numerous modest-effect variants collectively contributed to adaptation to food-limited environments during long sea voyages. More recently, however, selection pressures may have shifted toward lower BMI, indicating a potential evolutionary mismatch between past adaptations and modern environments.