Positive Selection on a Regulatory Insertion–Deletion Polymorphism inFADS2Influences Apparent Endogenous Synthesis of Arachidonic Acid
| Autor: | Kaixiong Ye, Kumar S.D. Kothapalli, Hui Gyu Park, Kinsley Ojukwu, Alon Keinan, Kalpana Joshi, Carlson Susan E, Ji Yao Zhang, Stephanie S. Hyon, Zhenglong Gu, Maithili S. Gadgil, J. Thomas Brenna, Kimberly O. O'Brien, James Zou |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Fatty Acid Desaturases Male 0301 basic medicine FADS1 FADS2 Linoleic acid Population Biology Polymorphism Single Nucleotide Young Adult 03 medical and health sciences chemistry.chemical_compound Delta-5 Fatty Acid Desaturase Gene Frequency INDEL Mutation positive selection population divergence Genotype Genetics Humans indel (insertion–deletion) Selection Genetic education Molecular Biology Allele frequency Discoveries Alleles Phospholipids Ecology Evolution Behavior and Systematics education.field_of_study Arachidonic Acid Haplotype Genetic Variation Genotype frequency 030104 developmental biology Haplotypes chemistry Fatty Acids Unsaturated Female Databases Nucleic Acid long chain polyunsaturated fatty acids |
| Zdroj: | Molecular Biology and Evolution |
| ISSN: | 1537-1719 0737-4038 |
| DOI: | 10.1093/molbev/msw049 |
| Popis: | Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion–deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product–precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice. |
| Databáze: | OpenAIRE |
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