Selection in Europeans on Fatty Acid Desaturases Associated with Dietary Changes

被引:74
作者
Buckley, Matthew T. [1 ,2 ]
Racimo, Fernando [1 ,2 ]
Allentoft, Morten E. [3 ]
Jensen, Majken K. [4 ,5 ]
Jonsson, Anna [6 ]
Huang, Hongyan [7 ]
Hormozdiari, Farhad [8 ]
Sikora, Martin [3 ]
Marnetto, Davide [9 ]
Eskin, Eleazar [8 ,10 ]
Jorgensen, Marit E. [11 ,12 ]
Grarup, Niels [6 ]
Pedersen, Oluf [6 ]
Hansen, Torben [6 ]
Kraft, Peter [7 ]
Willerslev, Eske [3 ]
Nielsen, Rasmus [1 ,2 ,3 ]
机构
[1] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA
[3] Univ Copenhagen, Nat Hist Museum Denmark, Copenhagen K, Denmark
[4] Harvard Med Sch, Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA
[5] Harvard Med Sch, Channing Div Network Med, Brigham & Womens Hosp, Boston, MA USA
[6] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn,Ctr Basic Metab Res, Copenhagen O, Denmark
[7] Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA
[8] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA
[9] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy
[10] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA
[11] Univ Southern Denmark, Natl Inst Publ Hlth, Copenhagen, Denmark
[12] Steno Diabet Ctr Copenhagen, Gentofte, Denmark
基金
美国国家卫生研究院;
关键词
selection; evolution; human; genetics; FADS; GENOME-WIDE; DOCOSAHEXAENOIC ACID; OMEGA-3; METABOLISM; EXPRESSION; DISEASE; RISK; POLYMORPHISMS; VISUALIZATION; NEANDERTHAL;
D O I
10.1093/molbev/msx103
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
FADS genes encode fatty acid desaturases that are important for the conversion of short chain polyunsaturated fatty acids (PUFAs) to long chain fatty acids. Prior studies indicate that the FADS genes have been subjected to strong positive selection in Africa, South Asia, Greenland, and Europe. By comparing FADS sequencing data from present-day and Bronze Age (5-3k years ago) Europeans, we identify possible targets of selection in the European population, which suggest that selection has targeted different alleles in the FADS genes in Europe than it has in South Asia or Greenland. The alleles showing the strongest changes in allele frequency since the Bronze Age show associations with expression changes and multiple lipid-related phenotypes. Furthermore, the selected alleles are associated with a decrease in linoleic acid and an increase in arachidonic and eicosapentaenoic acids among Europeans; this is an opposite effect of that observed for selected alleles in Inuit from Greenland. We show that multiple SNPs in the region affect expression levels and PUFA synthesis. Additionally, we find evidence for a gene-environment interaction influencing low-density lipoprotein (LDL) levels between alleles affecting PUFA synthesis and PUFA dietary intake: carriers of the derived allele display lower LDL cholesterol levels with a higher intake of PUFAs. We hypothesize that the selective patterns observed in Europeans were driven by a change in dietary composition of fatty acids following the transition to agriculture, resulting in a lower intake of arachidonic acid and eicosapentaenoic acid, but a higher intake of linoleic acid and alpha-linolenic acid.
引用
收藏
页码:1307 / 1318
页数:12
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