Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems

BACKGROUND Prokaryotes have evolved multiple systems to combat invaders such as viruses and plasmids. Examples of such defense systems include receptor masking, restriction-modification (R-M) systems, DNA interference (Argonaute), bacteriophage exclusion (BREX or PGL), and abortive infection, all of which act in an innate, nonspecific manner. In addition, prokaryotes have evolved adaptive, heritable immune systems: clustered regularly interspaced palindromic repeats (CRISPR) and the CRISPR-associated proteins (CRISPR-Cas). Adaptive immunity is conferred by the integration of DNA sequences from an invading element into the CRISPR array (adaptation), which is transcribed into long pre-CRISPR RNAs (pre-crRNAs)…

• SF
  Simons Foundation
• PG
  Paul G. Allen Family Foundation
• NY
  New York Stem Cell Foundation
• VF
  Vallee Foundation
• NI
  National Institute of Mental Health

  Awards: 1R01-MH110049, 5DP1-MH100706
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Award: 5R01DK097768-03