Reconstruction of the human amylase locus reveals ancient duplications seeding modern-day variation
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.
Authors
- Olanrewaju Austine-Orimoloye (ORCID: https://orcid.org/0000-0002-4390-1437)
- Andy Wing Chun Pang (ORCID: https://orcid.org/0000-0002-0558-3802)
- Evan E. Eichler (ORCID: https://orcid.org/0000-0002-8246-4014)
- Jennifer Kordosky
- Petar Pajic (ORCID: https://orcid.org/0000-0002-6791-294X)
- Alex Hastie (ORCID: https://orcid.org/0000-0001-5829-2649)
- Pille Hallast (ORCID: https://orcid.org/0000-0002-0588-3987)
- Kwondo Kim (ORCID: https://orcid.org/0000-0001-8254-528X)
- Ann‐Marie Torregrossa (ORCID: https://orcid.org/0000-0002-9327-9885)
- Charikleia Karageorgiou (ORCID: https://orcid.org/0000-0002-6998-6926)
- Sarah Hunt (ORCID: https://orcid.org/0000-0002-8350-1235)
- William T. Harvey (ORCID: https://orcid.org/0000-0003-0646-7528)
- Peter A. Audano (ORCID: https://orcid.org/0000-0002-5187-0415)
- Alexandra P. Lewis (ORCID: https://orcid.org/0000-0002-6195-4786)
- Kendra Hoekzema (ORCID: https://orcid.org/0000-0002-8058-0177)
- Tobias Marschall (ORCID: https://orcid.org/0000-0002-9376-1030)
- Jan O. Korbel (ORCID: https://orcid.org/0000-0002-2798-3794)
- Feyza Yilmaz (ORCID: https://orcid.org/0000-0001-8795-5800)
- Katherine M. Munson (ORCID: https://orcid.org/0000-0001-8413-6498)
- Christine R. Beck (ORCID: https://orcid.org/0000-0001-7821-8489)
- Ömer Gökçümen (ORCID: https://orcid.org/0000-0003-4371-679X)
- Charles Lee (ORCID: https://orcid.org/0000-0001-7317-6662)
- Kendra Scheer
Institutions
- University of Connecticut (US)
- Jackson Laboratory (US)
- University at Buffalo, State University of New York (US)
- UConn Health (US)
Publication Details
- Journal
- Science
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1126/science.adn0609
- Citations
- 42
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 25.18
Funders
- National Science Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Human Genome Research Institute
- NIH Office of the Director
- National Cancer Institute
- National Institute of Neurological Disorders and Stroke
- Common Fund