Lineage-specific expansions of TET/JBP genes and a new class of DNA transposons shape fungal genomic and epigenetic landscapes

Abstract

TET/JBP dioxygenases oxidize methylpyrimidines in nucleic acids and are implicated in generation of epigenetic marks and potential intermediates for DNA demethylation. We show that TET/JBP genes are lineage-specifically expanded in all major clades of basidiomycete fungi, with the majority of copies predicted to encode catalytically active proteins. This pattern differs starkly from the situation in most other organisms that possess just a single or a few copies of the TET/JBP family. In most basidiomycetes, TET/ JBP genes are frequently linked to a unique class of transposons, KDZ (Kyakuja, Dileera, and Zisupton) and appear to have dispersed across chromosomes along with them. Several of these elements typically encode additional proteins, including a divergent version of the HMG domain. Analysis of their transposases shows that they contain a previously uncharacterized version of the RNase H fold with multiple distinctive Zn-chelating motifs and a unique insert, which are predicted to play roles in structural stabilization and target sequence recognition, respectively. We reconstruct the complex evolutionary history of TET/JBPs and associated transposons as involving multiple rounds of expansion with concomitant lineage sorting and loss, along with several capture events of TET/ JBP genes by different transposon clades. On a few occasions, these TET/JBP genes were also laterally transferred to certain Ascomycota, Glomeromycota, Viridiplantae, and Amoebozoa. One such is an inactive version, calnexin-independence factor 1 (Cif1), from Schizosaccharomyces pombe, which has been implicated in inducing an epigenetically transmitted prion state. We argue that this unique transposon-TET/JBP association is likely to play important roles in speciation during evolution and epigenetic regulation. methylcytosine | fungal evolution | DNA modification | genomic association I ntragenomic conflicts with diverse mobile elements have played a critical role in shaping cellular genomes (1). In eukaryotes, genomic rearrangements mediated by transposons in germ-line cells promote reproductive isolation of organisms and, accordingly, are implicated in speciation events (2, 3). The mobility of transposons has the potential to disrupt genes by insertion as well as to create new genes or to resurrect inactive ones. Indeed, genomic analyses have revealed that transposons are an important source for both regulatory elements and new DNA-binding domains in transcription factors and chromatin proteins across the tree of life (1, 4). Organisms show a diverse array of strategies to counter mobile elements, supporting the idea of a constant arms race between them and genomes. Some of these strategies, such as transcriptional silencing by chromatin modifications (e.g., histone methylation, DNA methylation) and posttranscriptional silencing using components of the RNAi machinery, are widespread across eukaryotes (5). In contrast, processes such as DNA elimination in the macronuclei of ciliates show a restricted phyletic distribution (6). Transpos...

Simultaneous sequencing of oxidized methylcytosines produced by TET/JBP dioxygenases in Coprinopsis cinerea

“…The C. cinerea genome contains a total of 47 TET/JBP genes (Table S1), most of which are part of Kyakuja transposons (8). At least 32 of the TET/JBP genes are predicted to encode catalytically active proteins, and 29 of them belong to "complete" Kyakuja elements defined as possessing the three core genes, encoding a transposase, the TET/JBP enzyme, and a protein with a divergent HMG domain (8) (Fig. 1A and Tables S1 and S2).…”

“…1A and Tables S1 and S2). The C. cinerea genome has two distinct paralogs of DNA cytosine methyltransferase 1 (DNMT1) (CC1G_01237 and CC1G_00579) that are present across all Agaricomycetes (mushrooms), but not other fungi (8). C. cinerea also encodes a third predicted DNA cytosine methylase (CC1G_00872, also called DNMT5) with a distinct architecture (8) which has been recently shown to methylate cytosines with a bias towards those in internucleosomal linker regions (27).…”

“…In addition, we found significant enrichment of oxi-mC at other mobile selfish elements in the C. cinerea genome. Among these are the DNA transposons Dileera and Zisupton, whose transposases are related to those of the Kyakuja elements (1,8). There are 14 copies of Dileera and 8 copies of Zisupton transposons in the C. cinerea genome, and the majority of them (57%) contain oxi-mC (an example is shown in Fig.…”

“…posons with genes encoding TET/JBP proteins (1,8,9,22). We show that oxi-mCs mark TET/JBP transposons and other repetitive elements in C. cinerea, and are also enriched at centromeres.…”

“…[5][6][7]. In metazoans, the TET/JBP family is represented by TET proteins, which are present in all animals that are known to possess DNA cytosine methylation (3,8,9). The three TET paralogs of vertebrates have been shown to catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) (2), which is progressively oxidized to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) (10)(11)(12).…”