PT  - JOURNAL ARTICLE
AU  - Johanna Klughammer
AU  - Daria Romanovskaia
AU  - Amelie Nemc
AU  - Annika Posautz
AU  - Charlotte Seid
AU  - Linda C. Schuster
AU  - Melissa C. Keinath
AU  - Juan Sebastian Lugo Ramos
AU  - Lindsay Kosack
AU  - Annie Evankow
AU  - Dieter Prinz
AU  - Stefanie Kirchberger
AU  - Bekir Ergüner
AU  - Paul Datlinger
AU  - Nikolaus Fortelny
AU  - Christian Schmidl
AU  - Matthias Farlik
AU  - Kaja Skjærven
AU  - Andreas Bergthaler
AU  - Miriam Liedvogel
AU  - Denise Thaller
AU  - Pamela A. Burger
AU  - Marcela Hermann
AU  - Martin Distel
AU  - Daniel L. Distel
AU  - Anna Kübber-Heiss
AU  - Christoph Bock
TI  - Comparative analysis of genome-scale, base-resolution DNA methylation profiles across 580 animal species
AID  - 10.1101/2022.06.18.496602
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.18.496602
4099  - http://biorxiv.org/content/early/2022/06/20/2022.06.18.496602.short
4100  - http://biorxiv.org/content/early/2022/06/20/2022.06.18.496602.full
AB  - 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.Competing Interest StatementThe optimized RRBS protocol that was used in this study (previously developed by Paul Datlinger and Christoph Bock) has been licensed to Diagenode s.a. (Liege, Belgium) and commercialized as a kit and service.