Evolutionary scenario for the origin of CRISPR-Cas systems. Homologous genes are color-coded and identified by a family name (names follow the classification from ). Names in bold are proposed systematic names including those propose in this work; "legacy names" are in regular font. The signature genes for CRISPR-Cas types are shown within green boxes, and for subtypes within red boxes. The bold letters above the genes show major categories of Cas proteins: L, large CASCADE subunit; S, small CASCADE subunit; R, RAMP CASCADE subunit; RE, RAMP family RNase involved in crRNA processing (experimentally characterized nucleases shown be asterisks); T, transcriptional regulator. Genes coding for inactivated (putative) polymerases are indicated by crosses. Major evolutionary events are shown in the corresponding branches. Broken lines denote alternative evolutionary scenarios for the origin of RAMPs.