Protein and DNA Modifications: Evolutionary Imprints of Bacterial Biochemical Diversification and Geochemistry on the Provenance of Eukaryotic Epigenetics

It has long been recognized that eukaryotes possess several subcellular systems with no apparent equivalents in the two prokaryotic domains (superkingdoms) (Dacks and Doolittle 2001; Best et al. 2004; Mans et al. 2004; Walsh and Doolittle 2005; Aravind et al. 2006; Cavalier-Smith 2009). Hence, a major challenge in modern biology has been to explain the provenance of these uniquely eukaryotic features. Among these, the extensive use of epigenetic information in regulatory systems is a key paradigm that has fructified in the past two decades (Richards and Elgin 2002; Allis et al. 2007; Kouzarides 2007; Grewal 2010). Broadly defined, epigenetics might be viewed as transmission of biologically significant information over and beyond what is encoded by the standard bases in DNA (i.e., genetic information). It has become increasingly clear that the nucleus is the primary center for encoding of epigenetic information in eukaryotes (Denhardt et al. 2005; Allis et al. 2007; Kouzarides 2007). Here, it largely occurs via covalent modifications of DNA or DNA-associated proteins (chromatin proteins). Eukaryotes also show certain less-understood cytoplasmic forms of epigenetic transmission. These include modifications of cytoskeletal proteins, protein-based templating (i.e., prionic transmission) (Beauregard et al. 2009), and RNA-based information transmission in phenomena such as paramutation in plants (Brzeski and Brzeska 2011) and postconjugation macronucleus regeneration in ciliates (Mochizuki 2010). Epigenetic information impinges on fundamental aspects of eukaryotic biology such as DNA replication, DNA-damage repair, transcription of specific genes, global control of gene expression, splicing and other types of RNA processing, and exhibition of metabolically or structurally distinct cellular states (Richards and Elgin 2002; Allis et al. 2007; Kouzarides 2007; Grewal 2010). In specialized eukaryotes, such as parasites, epigenetic information plays an important role in the display of variable cell-surface antigens to evade host immunity (Duraisingh et al. 2005; Jiang et al. 2013). In multicellular forms such information is central to maintenance of a structured body plan (Muller et al. 2002; Gehring et al. 2006; Allis et al. 2007), dedicated immune systems (Cedar and Bergman 2011), and phenomena such as neural memory in animals (Landry et al. 2013). Epigenetic modifications of secreted proteins paralleling those of chromatin proteins have also been shown to be the primary determinants for specification of structures of unique biomineralized matrices such as bones (Tagliabracci et al. 2013) and siliceous shells of diatoms (Kroger et al. 2002; Sumper et al. 2007). Thus, understanding the origins of epigenetics is a major element in reconstructing eukaryote origins, including the emergence of their quintessential feature, the nucleus. Here, we offer a synthetic perspective on the origin of DNA and protein modification systems used to transmit epigenetic information in eukaryotes. Based on results from comparative genomics we emphasize their pervasive connections to bacterial secondary metabolism and interorganismal and genomic conflict systems.