@article {330726,
	title = {Reconstruction of the human amylase locus reveals ancient duplications seeding modern-day variation},
	journal = {Science},
	year = {2024},
	note = {<p>doi: 10.1126/science.adn0609</p>
},
	month = {2024/11/22},
	pages = {eadn0609},
	abstract = {<p>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 KYA, has seeded rapidly evolving rearrangements through recurrent non-allelic homologous recombination. Additionally, haplotypes with more than three AMY1 copies have significantly increased in frequency among European farmers over the past 4,000 years, potentially as an adaptive response to increased starch digestion.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 KYA, has seeded rapidly evolving rearrangements through recurrent non-allelic homologous recombination. Additionally, haplotypes with more than three AMY1 copies have significantly increased in frequency among European farmers over the past 4,000 years, potentially as an adaptive response to increased starch digestion.</p>
},
	doi = {https://doi.org/10.1126/science.adn0609},
	url = {https://www.science.org/doi/10.1126/science.adn0609},
	author = {Yilmaz, Feyza and Karageorgiou, Charikleia and Kim, Kwondo and Pajic, Petar and Scheer, Kendra and Human Genome Structural Variation Consortium and Beck, Christine R. and Torregrossa, Ann-Marie and Lee, Charles and Gokcumen, Omer and Audano, Peter A. and Austine-Orimoloye, Olanrewaju and Beck, Christine R. and Eichler, Evan E. and Hallast, Pille and Harvey, William T. and Hastie, Alex R. and Hoekzema, Kendra and Hunt, Sarah and Korbel, Jan O. and Kordosky, Jennifer and Lee, Charles and Lewis, Alexandra P. and Marschall, Tobias and Munson, Katherine M. and Pang, Andy and Yilmaz, Feyza}
}
