Multiple alignment of the MORCs, MGHKls and some characterized GHKL domains. Jpred predicted Secondary structure is shown above the alignment. The 75% consensus shown below the alignment was derived using the following classes of amino acids: hydrophobic (h: ALICVMYFW, yellow shading); the aliphatic subset of the hydrophobic class (l: LIV, yellow shading); hydrophobic (h: ACFILMVWY, yellow shading); small (s: ACDGNPSTV, green); the tiny subset of the small class (u: GAS, green); polar (p: CDEHKNQRST, blue); alcohol subset of polar (o: ST, brown); charged subset of polar (c: DEHKR, pink); positive subset of polar (+: HKR, pink). Amino acids in red background are completely conserved. Different subgroups of MORCS are indicated at the right end of the alignment. The sequences are denoted by their gene name followed by species abbreviation and GenBank Identifier separated by underscores. The species abbreviations are: Abac: Acidobacteria bacterium; Atha: Arabidopsis thaliana; Avar: Anabaena variabilis; Bpum: Bacillus pumilus; Bsp.: Bacillus sp.; Bsp.: Bradyrhizobium sp.; Btau: Bos taurus; Buni: Bacteroides uniformis; Bwei: Bacillus weihenstephanensis; Cbar: Clostridium bartlettii; Cbot: Clostridium botulinum; Ccre: Caulobacter crescentus; Cele: Caenorhabditis elegans; Cjej: Campylobacter jejuni; Clit: Congregibacter litoralis; Cpar: Cryptosporidium parvum; Drer: Danio rerio; Fnuc: Fusobacterium nucleatum; Fpsy: Flavobacterium psychrophilum; Glov: Geobacter lovleyi; Gthe: Geobacillus thermodenitrificans; Hsap: Homo sapiens; Jsp.: Janibacter sp.; Jsp.: Jannaschia sp.; Lbla: Leeuwenhoekiella blandensis; Lwel: Listeria welshimeri; Mace: Methanosarcina acetivorans; Mpen: Mycoplasma penetrans; Msp.: Marinobacter sp.; Nsp.: Nitrobacter sp.; Nvec: Nematostella vectensis; Oihe: Oceanobacillus iheyensis; Pcry: Psychrobacter cryohalolentis; Pflu: Pseudomonas fluorescens; Pmar: Prochlorococcus marinus; Pput: Pseudomonas putida; Pvib: Prosthecochloris vibrioformis; Retl: Rhizobium etli; Rpal: Rhodopseudomonas palustris; Rsol: Ralstonia solanacearum; Save: Streptomyces avermitilis; Ssp.: Sulfurovum sp.; Stro: Salinispora tropica; Tcru: Thiomicrospira crunogena; Tden: Treponema denticola; Vcho: Vibrio cholerae

Gene neighborhoods, domain architectures and contextual information graph of MORCS and related GHKL families. A) The gene neighborhoods are shown for selected MORCs (left panel) and paraMORCS (right panel). The direction of arrows indicates transcriptional direction and dots indicate intervening regions that might contain additional genes. Representative gene names are shown below each operon type. B) Representative domain architectures of MORCs and related proteins are shown. SMC_hinge: Structural maintenance of chromosome protein hinge domain; HTH: helix-turn-helix domain; BAM: Bromo-associated motif (also known as bromo-associated homology domain); TAM/MBD: C-methyl-DNA-binding domain; Z1, Z2, Z3 and X1, X2, X3 are uncharacterized domains. C) Ordered graph showing contextual information from gene neighborhoods and domain architectures. Solid arrows indicated information from domain architectures and dotted lines indicate information from gene neighborhoods. The direction of arrows denotes the order of genes in operons or order of domains in proteins from N-terminal to C-terminal. Red edges correspond to physical interactions between the domains. Genes are shown with hexagons and domains are shown as rounded rectangles. The domain coloring highlights the major contextual themes that are consistently seen with these proteins even if the actual domains belong to different families or are structurally distinct. For example, domains occurring only in eukaryotes are in yellow, nucleases are colored pink, methylases in green and non-GHKL ATPases in blue. Standard gene names are used. Additional Gene name abbreviations include: DAM: DNA Adenine Methylase; DCM: DNA Cytosine Methylase; HKD: possible nuclease domain of Phospholipase D fold; NRE: Novel Restriction Endonuclease; T2ENDO: Type II Endonuclease; pMORC: paraMORC; AIPR: Abortive infection phage resistance protein, a protein commonly encoded by numerous RM operons. Species abbrevations are as in Figure 1. Additional abbreviations are as follows: CPel: Candidatus Pelagibacter; Esp.: Erythrobacter sp.; Fjoh: Flavobacterium johnsoniae; Gura: Geobacter uraniireducens; Nmob: Nitrococcus mobilis; Otau: Ostreococcus tauri; Rsp.: Roseovarius sp.; Veis: Verminephrobacter eiseniae.