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Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for the development and function of the human brain. They can be obtained directly from food, e.g., fish, or synthesized from precursor molecules found in vegetable oils. To determine the importance of genetic variability to fatty-acid biosynthesis, we studied FADS1 and FADS2, which encode rate-limiting enzymes for fatty-acid conversion. We performed genome-wide genotyping (n = 5,652 individuals) and targeted resequencing (n = 960 individuals) of the FADS region in five European population cohorts. We also analyzed available genomic data from human populations, archaic hominins, and more distant primates. Our results show that present-day humans have two common FADS haplotypes-defined by 28 closely linked SNPs across 38.9 kb-that differ dramatically in their ability to generate LC-PUFAs. No independent effects on FADS activity were seen for rare SNPs detected by targeted resequencing. The more efficient, evolutionarily derived haplotype appeared after the lineage split leading to modern humans and Neanderthals and shows evidence of positive selection. This human-specific haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and thereby might have provided an advantage in environments with limited access to dietary LC-PUFAs. In the modern world, this haplotype has been associated with lifestyle-related diseases, such as coronary artery disease.

Original publication

DOI

10.1016/j.ajhg.2012.03.014

Type

Journal article

Journal

Am J Hum Genet

Publication Date

04/05/2012

Volume

90

Pages

809 - 820

Keywords

Adaptation, Physiological, Amino Acid Sequence, Animals, Croatia, Cross-Sectional Studies, Diet, European Continental Ancestry Group, Fatty Acid Desaturases, Fatty Acids, Omega-3, Fatty Acids, Omega-6, Haplotypes, Humans, Italy, Life Style, Molecular Sequence Data, Multigene Family, Neanderthals, Phylogeography, Polymorphism, Single Nucleotide, Risk Factors, Scotland, Sequence Analysis, DNA, Sweden