Genome-wide methylation is modified by caloric restriction in Daphnia magna

Jack Hearn,Mark Blaxter,Tom J Little,Philip J Wilson,Marianne Pearson

doi:10.1186/s12864-019-5578-4

Abstract

BackgroundThe degradation of epigenetic control with age is associated with progressive diseases of ageing, including cancers, immunodeficiency and diabetes. Reduced caloric intake slows the effects of ageing and age-related disease in vertebrates and invertebrates, a process potentially mediated by the impact of caloric restriction on epigenetic factors such as DNA methylation. We used whole genome bisulphite sequencing to study how DNA methylation patterns change with diet in a small invertebrate, the crustacean Daphnia magna. Daphnia show the classic response of longer life under caloric restriction (CR), and they reproduce clonally, which permits the study of epigenetic changes in the absence of genetic variation.ResultsGlobal cytosine followed by guanine (CpG) methylation was 0.7–0.9%, and there was no difference in overall methylation levels between normal and calorie restricted replicates. However, 333 differentially methylated regions (DMRs) were evident between the normally fed and CR replicates post-filtering. Of these 65% were hypomethylated in the CR group, and 35% were hypermethylated in the CR group.ConclusionsOur results demonstrate an effect of CR on the genome-wide methylation profile. This adds to a growing body of research in Daphnia magna that demonstrate an epigenomic response to environmental stimuli. Specifically, gene Ontology (GO) term enrichment of genes associated with hyper and hypo-methylated DMRs showed significant enrichment for methylation and acyl-CoA dehydrogenase activity, which are linked to current understanding of their roles in CR in invertebrate model organisms.

Highlights

The degradation of epigenetic control with age is associated with progressive diseases of ageing, including cancers, immunodeficiency and diabetes
Trimmed bisulphite-converted reads aligned to the D. magna strain 32 converted genome [48] using Bismark [59] exhibited lower mapping efficiencies than standard short-read alignments, as is typical of whole genome bisulphite sequencing (WGBS) [60], with 20–32% of reads not aligning to the reference genome (Additional files 1 and 2)
These CHH and CHG site containing reads were removed from analyses, as D. magna contains negligible CHH/G methylation [29] meaning they are indicative of bisulphite unconverted reads

Summary

Introduction

The degradation of epigenetic control with age is associated with progressive diseases of ageing, including cancers, immunodeficiency and diabetes. Reduced caloric intake slows the effects of ageing and agerelated disease in vertebrates and invertebrates, a process potentially mediated by the impact of caloric restriction on epigenetic factors such as DNA methylation. We used whole genome bisulphite sequencing to study how DNA methylation patterns change with diet in a small invertebrate, the crustacean Daphnia magna. Epigenetic modifications play a key role in patterning gene expression and organismal development. This is evident when epigenetic control degrades, resulting in progressive diseases in humans, including cancers, immunodeficiency and diabetes [1]. As the model organism Drosophila melanogaster, along with other surveyed Dipterans, exhibits negligible CpG methylation [18]

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Discussion

Conclusion