DNA methylation enables transposable element-driven genome expansion

Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19359-19366. doi: 10.1073/pnas.1921719117. Epub 2020 Jul 27.


Multicellular eukaryotic genomes show enormous differences in size. A substantial part of this variation is due to the presence of transposable elements (TEs). They contribute significantly to a cell's mass of DNA and have the potential to become involved in host gene control. We argue that the suppression of their activities by methylation of the C-phosphate-G (CpG) dinucleotide in DNA is essential for their long-term accommodation in the host genome and, therefore, to its expansion. An inevitable consequence of cytosine methylation is an increase in C-to-T transition mutations via deamination, which causes CpG loss. Cytosine deamination is often needed for TEs to take on regulatory functions in the host genome. Our study of the whole-genome sequences of 53 organisms showed a positive correlation between the size of a genome and the percentage of TEs it contains, as well as a negative correlation between size and the CpG observed/expected (O/E) ratio in both TEs and the host DNA. TEs are seldom found at promoters and transcription start sites, but they are found more at enhancers, particularly after they have accumulated C-to-T and other mutations. Therefore, the methylation of TE DNA allows for genome expansion and also leads to new opportunities for gene control by TE-based regulatory sites.

Keywords: DNA methylation; genome size; transposable element.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CpG Islands
  • Cytosine / metabolism
  • DNA Methylation*
  • DNA Transposable Elements
  • Eukaryota / genetics*
  • Eukaryota / metabolism
  • Gene Expression Regulation
  • Genome Size
  • Genome*
  • Mutation
  • Promoter Regions, Genetic


  • DNA Transposable Elements
  • Cytosine