{"doi":"10.1101/2023.12.21.572802","title":"Annelid methylomes reveal ancestral developmental and ageing-associated epigenetic erosion across Bilateria","abstract":"<jats:title>Abstract</jats:title>\n                <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as ‘mosaic’. Yet, the role and developmental dynamics of 5mC and how these explain interspecific differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>\n                    Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, and there is a gradual and global, age-dependent demethylation in adult stages. Moreover, reducing 5mC levels with cytidine analogues during early development impairs normal embryogenesis and reactivates TEs in the annelid\n                    <jats:italic>Owenia fusiformis</jats:italic>\n                    .\n                  </jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>Our study indicates that global epigenetic erosion during development and ageing is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.</jats:p>\n                </jats:sec>","journal":null,"year":null,"id":681409,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1780324,"name":"Luke A. Sarre","orcid":"0000-0002-5046-065X","position":1,"is_corresponding":false},{"id":1490363,"name":"Allan M. Carrillo‐Baltodano","orcid":"0000-0001-6297-8782","position":2,"is_corresponding":false},{"id":1490361,"name":"Billie E. Davies","orcid":"0000-0003-4039-8239","position":3,"is_corresponding":false},{"id":289801,"name":"Lan Xu","orcid":"0000-0002-9909-7660","position":4,"is_corresponding":false},{"id":1490365,"name":"Yan Liang","orcid":"0000-0003-2365-1239","position":5,"is_corresponding":false},{"id":1780327,"name":"Francisco M. Martín-Zamora","orcid":"0000-0002-2558-3762","position":6,"is_corresponding":false},{"id":1780328,"name":"Paul J. Hurd","orcid":"0000-0003-1112-9347","position":7,"is_corresponding":false},{"id":1103041,"name":"Alex de Mendoza","orcid":"0000-0002-6441-6529","position":8,"is_corresponding":false},{"id":1490369,"name":"José M. Martín‐Durán","orcid":"0000-0002-2572-1061","position":9,"is_corresponding":false},{"id":1490364,"name":"Kero Guynes","orcid":"0000-0002-0736-1656","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Annelid methylomes reveal ancestral developmental and ageing-associated epigenetic erosion across Bilateria","abstract":"<jats:title>Abstract</jats:title>\n                <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as ‘mosaic’. Yet, the role and developmental dynamics of 5mC and how these explain interspecific differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla.</jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>\n                    Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, and there is a gradual and global, age-dependent demethylation in adult stages. Moreover, reducing 5mC levels with cytidine analogues during early development impairs normal embryogenesis and reactivates TEs in the annelid\n                    <jats:italic>Owenia fusiformis</jats:italic>\n                    .\n                  </jats:p>\n                </jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>Our study indicates that global epigenetic erosion during development and ageing is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.</jats:p>\n                </jats:sec>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26207759","pmcid":null,"openalex_id":"https://openalex.org/W4390191426","authors":[],"funders":[{"funder_name":"European Research Council","grant_id":"801669","title":"Evolution of cell fate specification modes in spiral cleavage"},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/T008709/1","title":"London Interdisciplinary Doctoral Programme"},{"funder_name":"European Research Council","grant_id":"950230","title":"Deciphering the evolution and roles of cytosine DNA methylation across eukaryotes"},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/L023164/1","title":"The epigenetic basis of nutrition-mediated caste identity in the honeybee"},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/V009311/1","title":"The Role of Nutrition as an Epigenetic Modulator of Phenotypic Plasticity during Honeybee Development"}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2024/01/13/2023.12.21.572802.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2024/01/13/2023.12.21.572802.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2023.12.21.572802","host_type":"publisher"},{"url":"https://doi.org/10.1101/2023.12.21.572802","host_type":"repository"},{"url":"https://europepmc.org/article/PPR/PPR778687","host_type":"Europe_PMC"},{"url":"https://europepmc.org/api/fulltextRepo?pprId=PPR778687&type=FILE&fileName=EMS193131-pdf.pdf&mimeType=application/pdf","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1186/s13059-024-03346-z","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/39090757","host_type":""},{"url":"http://dx.doi.org/10.1186/s13059-024-03346-z","host_type":""},{"url":"https://doaj.org/article/20a431888cef488aa839a5075a92be08","host_type":""},{"url":"https://doi.org/https://doi.org/10.1186/s13059-024-03346-z","host_type":""}],"fields_of_study":["Epigenetics and DNA Methylation","Protist diversity and phylogeny","Marine Biology and Ecology Research","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Bilateria","Biology","DNA methylation","Brachyury","Evolutionary biology","Annelid","Epigenetics","Developmental biology","Genetics","Phylogenetics","Gene","Zoology","Mesoderm","Gene expression","Aging","QH301-705.5","Research","Annelida","Whole-genome bisulfite sequencing","EM-seq","QH426-470","Epigenesis, Genetic","Evolution, Molecular","Epigenome","Spiral cleavage","5-Methylcytosine","DNA Transposable Elements","Animals","Biology (General)","Phylogeny","Spiralia"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gca"},{"name":"pfam"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T17:45:36.178784Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}