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

• 成果类型: Article
• 署名作者: Yilmaz, Feyza; Karageorgiou, Charikleia; Kim, Kwondo; Pajic, Petar; Scheer, Kendra; Beck, Christine R.; Torregrossa, Ann-Marie; Lee, Charles; Gokcumen, Omer
• 署名单位: Jackson Laboratory; State University of New York (SUNY) System; University at Buffalo, SUNY; University of Connecticut; University of Connecticut; State University of New York (SUNY) System; University at Buffalo, SUNY; State University of New York (SUNY) System; University at Buffalo, SUNY
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13203
• DOI: 10.1126/science.adn0609
• 发表日期: 2024-11-22
• 关键词: genome sequence; human salivary; genetic history; r package; alignment; diversity; EVOLUTION; rearrangements; association; population

摘要

Previous studies suggested that the copy number of the human salivary amylase gene, AMY1, 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 AMY1 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 AMY1 copies have significantly increased in frequency among European farmers over the past 4000 years, potentially as an adaptive response to increased starch digestion.