Diversity and evolution of chromatin proteins encoded by DNA viruses

Abstract

Double-stranded DNA viruses display a great variety of proteins that interact with host chromatin. Using the wealth of available genomic and functional information, we have systematically surveyed chromatin-related proteins encoded by dsDNA viruses. The distribution of viral chromatin-related proteins is primarily influenced by viral genome size and the superkingdom to which the host of the virus belongs. Smaller viruses usually encode multifunctional proteins that mediate several distinct interactions with host chromatin proteins and viral or host DNA. Larger viruses additionally encode several enzymes, which catalyze manipulations of chromosome structure, chromatin remodeling and covalent modifications of proteins and DNA. Among these viruses, it is also common to encounter transcription factors and DNA-packaging proteins such as histones and IHF/HU derived from cellular genomes, which might play a role in constituting virus-specific chromatin states. Through all size ranges a subset of domains in viral chromatin proteins appears to have been derived from those found in host proteins. Examples include the Zn-finger domains of the E6 and E7 proteins of papillomaviruses, SET domain methyltransferases and Jumonji-related demethylases in certain nucleocytoplasmic large DNA viruses and BEN domains in poxviruses and polydnaviruses. In other cases, chromatin-interacting modules, such as the LXCXE motif, appear to have been widely disseminated across distinct viral lineages, resulting in similar retinoblastoma targeting strategies. Viruses, especially those with large linear genomes, have evolved a number of mechanisms to manipulate viral chromosomes in the process of replication-associated recombination. These include topoisomerases, Rad50/SbcC-like ABC ATPases and a novel recombinase system in bacteriophages utilizing RecA and Rad52 homologs. Larger DNA viruses also encode SWI2/SNF2 and A18-like ATPases which appear to play specialized roles in transcription and recombination. Finally, it also appears that certain domains of viral provenance have given rise to key functions in eukaryotic chromatin such as a HEH domain of chromosome tethering proteins and the TET/JBP-like cytosine and thymine hydroxylases.

Figure 1. Diversity of chromatin protein families among different lineages of dsDNA viruses

Labels at the top identify different genome size classes. Family names are the same as used in the main text and structural folds are given between parentheses. For the purpose of dividing the protein families according to spread and abundance among viral lineages (indicated by color codes), the Mimivirus was considered a lineage related to phycodnaviruses. Detailed description of each protein family is provided in the main text. Capsid/virion diameter data from [–169].

Figure 2. Domain architectures of the (A) LXCXE motif and the (B) BEN domain in DNA viruses

Standard nomenclature is used for domain names, poorly characterized globular domains are denoted as ‘X’. The architectures are labeled with the gene and species names of the virus in which they are found, separated by an underscore.

Figure 3. Cartoon representations and topology diagrams of various treble clef fold domains found in dsDNA viruses

Secondary structure elements of the shared core of the treble-clef fold are shown in color; helices are colored red and strands green. The characteristic N-terminal region of the treble-clef is colored blue. The unique helices and strands present only in certain representatives of the fold are shown in grey. Topology diagrams in the center depict the common and derived regions in the structures. The papillomavirus E6 Zn-finger is related to the LIM domain and the papillomavirus E7 Zn-finger is closest to the pygopus-like PHD fingers.

Figure 4. Gene neighborhoods and domain architectures of various chromatin domains found in double stranded DNA viruses

Genes are depicted as boxed arrows, with the arrowhead pointing from the 5’ to the 3’ end of the open reading frame. Domain architectures are shown as cartoon representations. Standard nomenclatures are used for both gene and domain names. Gene neighborhoods are labeled with the gene and species names of the primary domain discussed in the panel, separated by an underscore. The bar-graph in the top panel shows the genome position frequency of the SAP domain in completely sequenced viral genomes with linear chromosomes. There is a significant preference for positioning of this domain at one terminus of the viral chromosomes.