Adaptive Increase of Amylase Gene Copy Number in Peruvians Driven by Potato-rich Diets

The salivary amylase gene ( AMY1 ) exhibits remarkable copy number variation linked to dietary shifts in human evolution. While global studies highlight its structural complexity and association with starch-rich diets, localized selection patterns remain under explored. Here, we analyzed AMY1 copy number in 3,723 individuals from 84 populations, revealing that Indigenous Peruvian Andean populations possess the highest AMY1 copy number globally. A genome-wide analysis showed significantly higher amylase copy numbers in Peruvian Andean genomes compared to closely related populations. Further, we identified positive selection at the nucleotide level on a haplotype harboring at least five haploid AMY1 copies, with a Peruvian Andean-specific expansion dated to/shortly after potato domestication (∼6–10 kya). Using ultra-long-read sequencing, we demonstrated that recombination-based mutational mechanisms drive the formation of high-copy AMY1 haplotypes. Our study provides a framework for investigating structurally complex loci and their role in human dietary adaptation.