title: Adaptive evolution of the FADS gene cluster within Africa.
abstract: Long chain polyunsaturated fatty acids (LC-PUFAs) are essential for brain structure, development, and function, and adequate dietary quantities of LC-PUFAs are thought to have been necessary for both brain expansion and the increase in brain complexity observed during modern human evolution. Previous studies conducted in largely European populations suggest that humans have limited capacity to synthesize brain LC-PUFAs such as docosahexaenoic acid (DHA) from plant-based medium chain (MC) PUFAs due to limited desaturase activity. Population-based differences in LC-PUFA levels and their product-to-substrate ratios can, in part, be explained by polymorphisms in the fatty acid desaturase (FADS) gene cluster, which have been associated with increased conversion of MC-PUFAs to LC-PUFAs. Here, we show evidence that these high efficiency converter alleles in the FADS gene cluster were likely driven to near fixation in African populations by positive selection ∼85 kya. We hypothesize that selection at FADS variants, which increase LC-PUFA synthesis from plant-based MC-PUFAs, played an important role in allowing African populations obligatorily tethered to marine sources for LC-PUFAs in isolated geographic regions, to rapidly expand throughout the African continent 60-80 kya.
authors.affiliation: Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, United States of America. rmathias@jhmi.edu
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
authors.forename: Wenqing
authors.initials: W
authors.lastname: Fu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Akey
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Ainsworth
authors.forename: Dara G
authors.initials: DG
authors.lastname: Torgerson
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.forename: Susan
authors.initials: S
authors.lastname: Sergeant
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: Floyd H
authors.initials: FH
authors.lastname: Chilton
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000349:Africa; D044383:Black People / Q000235:genetics*; D019143:Evolution, Molecular; D044943:Fatty Acid Desaturases / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism; D005787:Gene Frequency; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D005231:Fatty Acids, Unsaturated; D044943:Fatty Acid Desaturases