Selection in Europeans on Fatty Acid Desaturases Associated with Dietary Changes.
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 α-linolenic acid.
Departments of Integrative Biology and Statistics, University of California Berkeley, Berkeley, CA.
Matthew T
MT
Buckley
Departments of Integrative Biology and Statistics, University of California Berkeley, Berkeley, CA.
Fernando
F
Racimo
Natural History Museum of Denmark, University of Copenhagen, Copenhagen K, Denmark.
Morten E
ME
Allentoft
Department of Nutrition, Harvard T.H. Chan School of Public Health & Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Majken K
MK
Jensen
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen Ø, Denmark.
Anna
A
Jonsson
Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA.
Hongyan
H
Huang
Department of Computer Science, University of California, Los Angeles, CA, USA.
Farhad
F
Hormozdiari
Natural History Museum of Denmark, University of Copenhagen, Copenhagen K, Denmark.
Martin
M
Sikora
Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy.
Davide
D
Marnetto
Department of Computer Science, University of California, Los Angeles, CA, USA.|Department of Human Genetics, University of California, Los Angeles, CA, USA.
Eleazar
E
Eskin
National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.|Steno Diabetes Center Copenhagen, Gentofte, Denmark.
Marit E
ME
Jørgensen
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen Ø, Denmark.
Niels
N
Grarup
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen Ø, Denmark.
Oluf
O
Pedersen
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen Ø, Denmark.
Torben
T
Hansen
Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA.
Peter
P
Kraft
Natural History Museum of Denmark, University of Copenhagen, Copenhagen K, Denmark.
Eske
E
Willerslev
Departments of Integrative Biology and Statistics, University of California Berkeley, Berkeley, CA.|Natural History Museum of Denmark, University of Copenhagen, Copenhagen K, Denmark.
Rasmus
R
Nielsen
D000483:Alleles; D000072441:DNA, Ancient / Q000032:analysis; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism; D019143:Evolution, Molecular; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D005227:Fatty Acids / Q000235:genetics* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D059647:Gene-Environment Interaction; D006801:Humans; D019787:Linoleic Acid / Q000235:genetics; D008055:Lipids / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
D000072441:DNA, Ancient; D004041:Dietary Fats; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008055:Lipids; D019787:Linoleic Acid; D044943:Fatty Acid Desaturases
FADS; evolution; genetics; human; selection