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Diet and the evolution of human amylase gene copy number variation


Starch consumption is a prominent characteristic of agricultural societies and hunter-gatherers in arid environments. In contrast, rainforest and circum-arctic hunter-gatherers and some pastoralists consume much less starch1,2,3. This behavioral variation raises the possibility that different selective pressures have acted on amylase, the enzyme responsible for starch hydrolysis4. We found that copy number of the salivary amylase gene (AMY1) is correlated positively with salivary amylase protein level and that individuals from populations with high-starch diets have, on average, more AMY1 copies than those with traditionally low-starch diets. Comparisons with other loci in a subset of these populations suggest that the extent of AMY1 copy number differentiation is highly unusual. This example of positive selection on a copy number–variable gene is, to our knowledge, one of the first discovered in the human genome. Higher AMY1 copy numbers and protein levels probably improve the digestion of starchy foods and may buffer against the fitness-reducing effects of intestinal disease.

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Figure 1: AMY1 copy number variation and salivary amylase protein expression.
Figure 2: Diet and AMY1 copy number variation.
Figure 3: High-resolution fiber FISH validation of AMY1 copy number estimates.
Figure 4: Japanese-Yakut copy number differentiation at AMY1 versus other genome-wide loci.


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We are grateful to all our study participants. We thank H. Cann and C. de Toma of the Fondation Jean Dausset (CEPH), the Cincinnati Zoo, the Lincoln Park Zoo, the New Iberia Research Center, the Primate Foundation of Arizona, the Southwest Foundation for Biomedical Research, the Coriell Institute for Medical Research and the Integrated Primate Biomaterials and Information Resource for samples. C. Tyler-Smith and Y. Gilad provided comments on a previous version of the manuscript. We would also like to thank the Wellcome Trust Sanger Institute Microarray Facility for printing the arrays and T. Fitzgerald and D. Rajan for technical support. This study was funded by grants from the L.S.B. Leakey Foundation and Wenner-Gren Foundation (to N.J.D.), the Department of Pathology, Brigham & Women's Hospital (to C.L.), the National Institutes of Health (to the University of Louisiana at Lafayette New Iberia Research Center; numbers RR015087, RR014491 and RR016483) and the Wellcome Trust (H.F., R.R. and N.P.C.).

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Authors and Affiliations



G.H.P. and N.J.D. contributed equally to this work. G.H.P., N.J.D., C.L. and A.C.S. designed the study; G.H.P., F.A.V., J.L.M. and A.C.S. collected the samples; G.H.P. and A.S.L. performed qPCR experiments; J.W. performed protein blot experiments; G.H.P. performed fiber FISH experiments; H.F. and R.R. performed and analyzed aCGH experiments; K.G.C. performed nucleotide sequencing experiments; G.H.P. performed data analyses; R.M., N.P.C., C.L. and A.C.S. supervised the experiments and analyses and G.H.P. and N.J.D. wrote the paper.

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Correspondence to Nathaniel J Dominy.

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Perry, G., Dominy, N., Claw, K. et al. Diet and the evolution of human amylase gene copy number variation. Nat Genet 39, 1256–1260 (2007).

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