Date Published: February 28, 2019
Publisher: Public Library of Science
Author(s): Magdalena Czajkowska, Paweł Brzęk, Paweł Dobrzyń, Catherine Mounier.
Fatty acyl composition of cell membrane lipids, particularly the abundance of highly unsaturated docosahexaenoic fatty acid (22:6n-3, DHA), is likely to be an important predictor of basal metabolic rate (BMR). Our study was performed using two lines of laboratory mice divergently selected for either high or low BMR. We describe a novel single nucleotide polymorphism in the Fads2 gene encoding Δ6-desaturase, a key enzyme in the metabolic pathways of polyunsaturated fatty acids (PUFAs). The allele frequencies of Fads2 were significantly different in both lines of mice. The analysis of genetic distances revealed that the genetic differentiation between the two studied lines developed significantly faster at the Fads2 locus than it did at neutral loci. Such a pattern suggests that the Fads2 polymorphism is related to the variation in BMR, i.e. the direct target of selection. The Fads2 polymorphism significantly affected abundance of several PUFAs; however, the differences in PUFA composition between lines were compatible with the difference in frequency of Fads2 alleles only for DHA. We hypothesize that the polymorphism in the Fads2 gene affects the BMR through modification of DHA abundance in cell membranes. This may be the first example of a significant link between a polymorphism in a gene responsible for fatty acyl composition and variation in BMR.
Intraspecific variation in the basal metabolic rate (BMR) plays a profound role in both evolution and medicine [1–3]. However, little is understood about its molecular and genetic background . Although BMR is a complex and polygenic trait , its intraindividual variation can sometimes be significantly modified by polymorphisms in a single gene .
In this study, we investigated the presence of polymorphism in genes controlling n-6 and n-3 PUFA metabolic pathways in mice selected divergently for either high or low BMR. We found one, nonsynonymous single nucleotide polymorphism (G/A) in the Fads2 gene. Strikingly, allele A occurred significantly more frequently in the L-BMR line than it did in the H-BMR line. Similarly, analysis of genetic distances based upon FST values revealed significant genetic differentiation at the Fads2 locus between lines L-BMR and H-BMR in both generations studied. However, the studied lines of mice were not replicated because maintaining several independent lines was not feasible due to the workload required by the BMR assays. Therefore, any differences in gene frequency between these two lines may potentially reflect the effect of genetic drift rather than selection . Nevertheless, the genetic differentiation (expressed as FST) between lines H-BMR and L-BMR in F22 was significantly greater at the Fads2 locus than it was at any of the 10 studied noncoding microsatellite loci (Fig 1). However, the average FST for neutral microsatellite loci increased between F22 and F32 (from 0.096 to 0.224), and the FST for Fads2 in F32 fell within the range of values observed for neutral loci. We conclude that the genetic variation between lines H-BMR and L-BMR developed significantly faster during the course of selection at the Fads2 locus than at neutral loci, though it was later masked by genetic drift effects. This pattern suggests that genetic polymorphism at the Fads2 gene is related to variation in BMR, i.e., the direct target of selection.