Deciphering the evolution and roles of cytosine DNA methylation across eukaryotes

ongoing

Cytosine DNA methylation is a major component of eukaryotic chromatin, yet extensive variation of methylation patterns occurs throughout eukaryotes. So far, the roles of DNA methylation have been mostly characterized in vertebrates, plants and fungi, where two common patterns have emerged as potentially ancestral within eukaryotes: methylation of silent transposable elements and methylation of constitutively transcribed genes (gene body methylation). However, the genes responsible for depositing methylation are not always orthologous across divergent lineages, so these common patterns could instead be the product of convergent evolution. To discern between these alternatives, we first need to correct the taxon sampling bias that hampers our understanding about the evolution of DNA methylation. In this project we will determine the roles of DNA methylation across vastly underexplored eukaryotic diversity. We will use state-of-the-art genomic techniques, experimental manipulations and computational analyses to trace the evolutionary conservation of methylation-dependent transposable element silencing across a wide range of unicellular eukaryotes, using methylation-depleting drugs and bisulfite sequencing. We will then assess the roles of gene body methylation in an invertebrate to unveil similarities with plants and shed light on why vertebrates transitioned to hypermethylated genomes. Finally, we will study the evolution of proteins able to bind and interpret DNA methylation across disparate eukaryotes, since ultimately these proteins link DNA methylation and its regulatory functions. Through linking experimental epigenomics to macro-evolutionary comparative genomics this project will reveal how different functions of DNA methylation assembled throughout evolution. In turn, this evolutionary perspective will allow a better understanding of the genome regulatory roles of this base modification and its impact on genome composition in plants and animals.