Convergent evolution of a vertebrate-like methylome in a marine sponge

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Vertebrates have highly methylated genomes at CpG positions, whereas invertebrates have sparsely methylated genomes. This increase in methylation content is considered a major regulatory innovation of vertebrate genomes. However, here we report that a sponge, proposed as the potential sister group to the rest of animals, has a highly methylated genome. Despite major differences in genome size and architecture, we find similarities between the independent acquisitions of the hypermethylated state. Both lineages show genome-wide CpG depletion, conserved strong transcription factor methyl-sensitivity and developmental methylation dynamics at 5-hydroxymethylcytosine enriched regions. Together, our findings trace back patterns associated with DNA methylation in vertebrates to the early steps of animal evolution. Thus, the sponge methylome challenges previous hypotheses concerning the uniqueness of vertebrate genome hypermethylation and its implications for regulatory complexity.

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Fig. 1: Amphimedon has a vertebrate-like methylome.
Fig. 2: Methyl-sensitive transcription factors are enriched at unmethylated Amphimedon promoters.
Fig. 3: Methylation dynamics during Amphimedon development.
Fig. 4: Genomic DNA hydroxymethylation is enriched at transcription factor binding sites in Amphimedon.

Data availability

Sequencing data have been deposited in Gene Expression Omnibus under the following accession number GSE124016.

Code availability

The code used to generate the analysis can be accessed at


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We thank J. M. Polo for critical reading of this manuscript. This work was supported by the Australian Research Council (ARC) Centre of Excellence programme in Plant Energy Biology (grant no. CE140100008). R.L. was supported by a Sylvia and Charles Viertel Senior Medical Research Fellowship, ARC Future Fellowship (no. FT120100862) and Howard Hughes Medical Institute International Research Scholarship. S.M.D. and B.M.D. were supported by grants from the ARC (grant nos. DP160100573 and DP170102353). Research in A.H.’s group was supported by the European Research Council Community’s Framework Program Horizon 2020 (2014–2020) ERC grant agreement (no. 648861) and an NSF IRFP Postdoctoral Fellowship (no. 1158629) to K.P. A.d.M. was funded by an EMBO long-term fellowship (no. ALTF 144-2014). U.T. was funded by a grant from the Austrian Science Fund FWF (grant no. P27353).

Author information

A.d.M. and R.L. designed the study. A.d.M. prepared methylC-seq, TAB-seq and DAP–seq libraries, with the help of O.B. and J.P. The data were analysed by A.d.M., with help from S.B. Amphimedon materials were provided by S.M.D., B.M.D. and W.L.H. Mnemiopsis materials were provided by K.P. and A.H. Sycon material was provided by S.L. and M.A. Nematostella material was provided by U.T. The manuscript was written by A.d.M. and R.L. All authors commented on the final manuscript.

Correspondence to Alex de Mendoza or Ryan Lister.

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