DNA methylation differs extensively between strains of the same geographical origin and changes with age in Daphnia magna

Jack Hearn, Fiona Plenderleith, Tom J. Little

Research output: Contribution to journalArticlepeer-review

Abstract

Background
Patterns of methylation influence lifespan, but methylation and life span may also depend on diet, or differ between genotypes. Prior to this study, interactions between diet and genotype have not been explored together to determine their influence on methylation. The invertebrate Daphnia magna is an excellent choice for testing the epigenetic response to the environment: parthenogenetic offspring are identical to their siblings (making for powerful genetic comparisons), they are relatively short-lived, and have well-characterised inter-strain life-history trait differences. We performed a survival analysis in response to caloric restriction and then undertook a 47replicate experiment testing the DNA methylation response to ageing and caloric restriction of two strains of D. magna.

Results
Methylated cytosines (CpGs) were most prevalent in exons two to five of gene-bodies. One strain exhibited a significantly increased lifespan in response to caloric restriction, but there was no effect of food level CpG methylation status. Inter-strain differences dominated the methylation experiment with over 15000 differently methylated CpGs. One gene, Me31b, was hypermethylated extensively in one strain and is a key regulator of embryonic expression. Sixty-one CpGs were differentially methylated between young and old individuals, including multiple CpGs within the histone H3 gene, which we rehypermethylated in old individuals. Across all Age-related CpGs, we identified a set that are highly correlated with chronological age.

Conclusions
Methylated cytosines are concentrated in early exons of gene sequences indicative of a directed, non-random, process despite the low overall DNA methylation percentage in this species. We identify no effect of caloric restriction on DNA methylation, contrary to our previous results and established impacts of caloric restriction on phenotype and gene expression. We propose our approach here is more robust in invertebrates given genome-wide CpG distributions. For both strain and ageing, a single gene emerges as differentially methylated that for each factor could have widespread phenotypic effects. Our data showed the potential for an epigenetic clock at a subset of age positions, which is exciting but requires confirmation.
Original languageEnglish
Article number4
Number of pages14
JournalEpigenetics and Chromatin
Volume14
DOIs
Publication statusPublished - 6 Jan 2021

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