Dietary adaptation of FADS genes in Europe varied across time and geography

Abstract

Fatty acid desaturase (FADS) genes encode rate-limiting enzymes for the biosynthesis of omega-6 and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). This biosynthesis is essential for individuals subsisting on LCPUFA-poor diets (for example, plant-based). Positive selection on FADS genes has been reported in multiple populations, but its cause and pattern in Europeans remain unknown. Here we demonstrate, using ancient and modern DNA, that positive selection acted on the same FADS variants both before and after the advent of farming in Europe, but on opposite (that is, alternative) alleles. Recent selection in farmers also varied geographically, with the strongest signal in southern Europe. These varying selection patterns concur with anthropological evidence of varying diets, and with the association of farming-adaptive alleles with higher FADS1 expression and thus enhanced LCPUFA biosynthesis. Genome-wide association studies reveal that farming-adaptive alleles not only increase LCPUFAs, but also affect other lipid levels and protect against several inflammatory diseases.

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Figure 1: Ancient DNA-based test for recent positive selection.
Figure 2: Tests for recent positive selection based solely on modern DNA.
Figure 3: Varying selection and frequency patterns between southern and northern Europe.
Figure 4: Temporal frequency pattern and selection signals in pre-Neolithic European hunter–gatherers.
Figure 5: Haplotype network and geographical frequency distribution.
Figure 6: Geographical frequency distribution for SNPs rs174594 and rs174570 in present-day global populations.

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Acknowledgements

We thank M. Slatkin and J. Schraiber for their help in running their software, D. Reich and I. Mathieson for making their data publicly available, L. Arbiza, C. Liang, D. Marburgh, E. Li, K. Kothapalli, T. Brenna and all the members of the Keinan laboratory for helpful discussion and comments on the manuscript. This work was supported by the National Institutes of Health (grants R01HG006849 and R01GM108805 to A.K.) and the Edward Mallinckrodt Jr Foundation (A.K.).

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Contributions

A.K. and K.Y. conceived and designed the project; K.Y. performed data collection and analysis, with contributions from D.W. and F.G.; K.Y. and A.K. interpreted the results, with contribution from O.B.-Y. on the anthropological perspective; K.Y. and A.K. wrote the manuscript. All authors read, edited and approved the final version of the manuscript.

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Correspondence to Alon Keinan.

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The authors declare no competing financial interests.

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Supplementary Notes; Supplementary Methods; Supplementary Tables 2–9; Supplementary Figures 1–32. (PDF 12959 kb)

Supplementary Table 1

Ancient DNAs used in this study. (XLSX 26 kb)

Supplementary Data 1

Computational scripts developed in this study. (ZIP 231 kb)

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Ye, K., Gao, F., Wang, D. et al. Dietary adaptation of FADS genes in Europe varied across time and geography. Nat Ecol Evol 1, 0167 (2017). https://doi.org/10.1038/s41559-017-0167

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