Adaptive evolution of the FADS gene cluster within Africa.

Rasika A Mathias,Susan Sergeant,Floyd H Chilton,Wenqing Fu,Ingo Ruczinski,Hannah C Ainsworth,Dara G Torgerson,Joshua M Akey,Kathleen C Barnes,Takeo Yoshikawa

doi:10.1371/journal.pone.0044926

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.

Highlights

Studies suggest that anatomically modern humans arose in Africa approximately 150 thousand years ago, expanded throughout Africa,60–80 kya, and to most parts of Europe and Asia,40 kya[1,2,3,4,5,6]
To investigate the evolutionary forces shaping patterns of variation in the fatty acid desaturase (FADS) gene cluster in geographically diverse populations, we analyzed 1092 individuals representing 14 populations sequenced as part of the 1000 Genomes Project (1 KGP; population-specific details shown in Table S1) and focused on a 300 kb region centered on the FADS loci
The current work confirms marked global differences in the allele frequencies of variants in the FADS gene cluster that was first noted in African Americans and European Americans [16,17], especially at variants strongly associated with the efficiency of conversion of LA and ALA to arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively

Summary

Introduction

Studies suggest that anatomically modern humans arose in Africa approximately 150 thousand years ago (kya), expanded throughout Africa ,60–80 kya, and to most parts of Europe and Asia ,40 kya[1,2,3,4,5,6]. Numerous mitochondrial DNA studies support what Foster and Matsumera [5] describe as a ‘remarkable expansion’ from a small geographic region dating broadly to ,60–80 kya. This expansion occurred at a period of time when archeological evidence indicates great advances in technological, social, and cognitive behavior [7]. 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 [8]. What facilitated the movement away from stable sources of DHA and expansions into a wide range of environmental (including arid) conditions?

Methods

Results

Conclusion