Genetic adaptation of fatty-acid metabolism: A human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids

Adam Ameur, Stefan Enroth, Asa Johansson, Ghazal Zaboli, Wilmar Igl, Anna C V Johansson, Manuel A Rivas, Mark J Daly, Gerd Schmitz, Andrew A Hicks, Thomas Meitinger, Lars Feuk, Cornelia van Duijn, Ben Oostra, Peter P Pramstaller, Igor Rudan, Alan F Wright, James F Wilson, Harry Campbell, Ulf Gyllensten

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish
Pages (from-to)809-820
Number of pages12
JournalAmerican Journal of Human Genetics
Volume90
Issue number5
DOIs
Publication statusPublished - 4 May 2012

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

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