Reconstruction of the human amylase locus reveals ancient duplications seeding modern-day variation

Abstract

Previous studies suggested that the copy number of the human salivary amylase gene, <i>AMY1</i>, correlates with starch-rich diets. However, evolutionary analyses are hampered by the absence of accurate, sequence-resolved haplotype variation maps. We identified 30 structurally distinct haplotypes at nucleotide resolution among 98 present-day humans, revealing that the coding sequences of <i>AMY1</i> copies are evolving under negative selection. Genomic analyses of these haplotypes in archaic hominins and ancient human genomes suggest that a common three-copy haplotype, dating as far back as 800,000 years ago, has seeded rapidly evolving rearrangements through recurrent nonallelic homologous recombination. Additionally, haplotypes with more than three <i>AMY1</i> copies have significantly increased in frequency among European farmers over the past 4000 years, potentially as an adaptive response to increased starch digestion.