Comparative analysis of genome-scale, base-resolution DNA methylation profiles across 580 animal species

Abstract

Methylation of cytosines is the prototypic epigenetic modification of the DNA. It has been implicated in various regulatory mechanisms throughout the animal kingdom and particularly in vertebrates. We mapped DNA methylation in 580 animal species (535 vertebrates, 45 invertebrates), resulting in 2443 genome-scale, base-resolution DNA methylation profiles of primary tissue samples from various organs. Reference-genome independent analysis of this comprehensive dataset quantified the association of DNA methylation with the underlying genomic DNA sequence throughout vertebrate evolution. We observed a broadly conserved link with two major transitions - once in the first vertebrates and again with the emergence of reptiles. Cross-species comparisons focusing on individual organs supported a deeply conserved association of DNA methylation with tissue type, and cross-mapping analysis of DNA methylation at gene promoters revealed evolutionary changes for orthologous genes with conserved DNA methylation patterns. In summary, this study establishes a large resource of vertebrate and invertebrate DNA methylomes, it showcases the power of reference-free epigenome analysis in species for which no reference genomes are available, and it contributes an epigenetic perspective to the study of vertebrate evolution.

Genome Skimming with Nanopore Sequencing Precisely Determines Global and Transposon DNA Methylation in Vertebrates

“…The most comprehensive previous study of animal methylation assayed 580 species and matches the global patterns presented here 35 . However, this impressive catalog was created using RRBS and is subject to the typical challenges caused by bisulfite conversion, as well as enrichment for CpG dense regions and lack of accurate transposon identification due to short reads and loss of mapping ability.…”

Epigenetics across the evolutionary tree: New paradigms from non‐model animals

“…Profiling samples collected following amputation revealed no significant changes in DNA methylation patterns, despite widespread transcriptomic and chromatin accessibility changes. [ 50 ] Thus, even during a physiological process that is characterized by dramatic changes in cell identity and behavior, the DNA methylation pattern remained unchanged. Another example provided by our studies of zebrafish mutants with DNA hypomethylation showed widespread gene expression changes, but none could be attributed to loss of promoter methylation.…”

Cadmium nitrate and DNA methylation in gastropods: comparison between ovotestis and hepatopancreas

“…In contrast, available evidence indicates that vertebrate genomes are predominantly heavily methylated ( Angeloni & Bogdanovic, 2021 ) and display cytosine DNA methylation at CpG dinucleotides, except for CpG sites from genomic regions with high CpG ratios and GC contents—regions also known as “CpG islands” (CGIs) ( Al Adhami et al, 2022 ). However, the paradigm of DNA methylation in invertebrates has been recently challenged as growing evidence shows that it is more sophisticated than previously assumed ( De Mendoza et al, 2019 ; Klughammer et al, 2022 ). A recent comparative analysis of DNA methylation profiles across 580 animal species (including 45 invertebrates) revealed that the total amount of 5mC in the genome of many invertebrates species is well within the levels seen in vertebrates ( Klughammer et al, 2022 ).…”

“…However, the paradigm of DNA methylation in invertebrates has been recently challenged as growing evidence shows that it is more sophisticated than previously assumed ( De Mendoza et al, 2019 ; Klughammer et al, 2022 ). A recent comparative analysis of DNA methylation profiles across 580 animal species (including 45 invertebrates) revealed that the total amount of 5mC in the genome of many invertebrates species is well within the levels seen in vertebrates ( Klughammer et al, 2022 ). The haplosclerid demosponge Amphimedon queenslandica (Hooper & Van Soest, 2006), for example, showed a hypermethylated genome, with methylation levels and patterns showing strong similarities with vertebrates ( De Mendoza et al, 2019 ).…”

“…Moreover, certain invertebrates ( e.g. , sea urchins) display the DNA methylation profiles specific to vertebrates; that is, low gene promoter methylation and elevated gene-body methylation ( Klughammer et al, 2022 ).…”