Selection in Europeans on Fatty Acid Desaturases Associated with Dietary Changes

Abstract

FADS genes encode fatty acid desaturases that are important for the conversion of short chain polyunsaturated fatty acids (PUFAs) to long chain fatty acids. Prior studies indicate that the FADS genes have been subjected to strong positive selection in Africa, South Asia, Greenland, and Europe. By comparing FADS sequencing data from present-day and Bronze Age (5–3k years ago) Europeans, we identify possible targets of selection in the European population, which suggest that selection has targeted different alleles in the FADS genes in Europe than it has in South Asia or Greenland. The alleles showing the strongest changes in allele frequency since the Bronze Age show associations with expression changes and multiple lipid-related phenotypes. Furthermore, the selected alleles are associated with a decrease in linoleic acid and an increase in arachidonic and eicosapentaenoic acids among Europeans; this is an opposite effect of that observed for selected alleles in Inuit from Greenland. We show that multiple SNPs in the region affect expression levels and PUFA synthesis. Additionally, we find evidence for a gene–environment interaction influencing low-density lipoprotein (LDL) levels between alleles affecting PUFA synthesis and PUFA dietary intake: carriers of the derived allele display lower LDL cholesterol levels with a higher intake of PUFAs. We hypothesize that the selective patterns observed in Europeans were driven by a change in dietary composition of fatty acids following the transition to agriculture, resulting in a lower intake of arachidonic acid and eicosapentaenoic acid, but a higher intake of linoleic acid and α-linolenic acid.

High-resolution comparative analysis of great ape genomes

“…4a). We also resolve a 65 kbp human-specific deletion in FADS1 and FADS2 , genes involved in fatty acid biosynthesis that have been the target of positive selection (36) and potential dietary changes in human evolution (37, 38). The deletion brings the promoters of FADS1 and FADS2 (major isoform) in closer proximity and shortens the first intron of the other two FADS2 isoforms (Fig.…”

A likelihood approach for uncovering selective sweep signatures from haplotype data

“…We expect that our simple yet powerful statistical model of selective sweeps will yield novel insights into the adaptive histories of diverse populations, and given its suitability to human data, will prove important in future analyses of understudied populations. To motivate this point, we highlight that insights into local adaptation within human populations continue to emerge [Hu et al, 2017, Buckley et al, 2017, Fan et al, 2019, more than a decade after the first investigations began [Ronald and Akey, 2005, Sabeti et al, 2006. To facilitate the adoption of our T statistic, we provide open-source software, titled LASSI (Likelihood-based Approach for Selective Sweep Inference; http://personal.psu.edu/mxd60/LASSI.html), which implements all stages of our methodology in a single efficient pipeline.…”

Transcriptome-wide association studies: opportunities and challenges

“…FADS2 -knockout mice had roughly doubled cholesterol synthesis rate in macrophages 43 and altered levels of multiple cholesterol esters in liver 44 . FADS3 is least well-characterized but has 52% and 62% sequence homology with FADS1 and FADS2, respectively 45 .…”