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SUMMARY:CRISPR-Cas: origin of adaptive immunity from selfish genetic eleme
 nts and the evolutionary continuum from Darwin to Lamarck - Eugene Koonin
DTSTART:20160318T110000Z
DTEND:20160318T120000Z
UID:TALK62582@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:The archaeal and bacterial CRISPR-Cas systems employ small gui
 de RNAs derived from foreign or self DNA for adaptive immunity against vir
 uses and plasmids and apparently\, in some case\, also for regulation of g
 ene expression. The RNA-guided Cas nucleases comprise the new generation o
 f genome editing tools and are often claimed to have ushered a revolution 
 in genetic engineering. The current classification of CRISPR-Cas systems i
 ncludes 4 types and 11 subtypes of Class 1\, with multisubunit effector co
 mplexes\, and 2 types and 4 subtypes of Class 2\, in which the effectors a
 re single\, multidomain proteins\, exemplified by the experimentally chara
 cterized Cas9 and Cpf1. We developed a computational pipeline for comprehe
 nsive identification of CRISPR-Cas loci in genomic and metagenomic sequenc
 es\, and employed it to search for novel Class 2 CRISPR-Cas systems. Four 
 new subtypes of type V and a new type VI with 3 subtypes were discovered. 
 The effectors of all type V systems contain the RuvC-like nuclease domain 
 that apparently was derived from TnpB proteins encoded in bacterial and ar
 chaeal transposons but unlike the type II effectors\, Cas9\, lack the seco
 nd\, HNH nuclease domain. The type VI effector each contain two predicted 
 HEPN RNase domains. The crRNA processing was experimentally demonstrated f
 or subtypes V-B and VI-A\, and in the case of V-B\, PAM-dependent interfer
 ence was also identified. Further experimental characterization of these a
 nd other newly discovered CRISPR-Cas variants is underway.  Sequence compa
 rison and phylogenetic analysis indicate that Class 2 CRISPR-Cas systems e
 volved on multiple occasions through recombination of Class 1 adaptation m
 odules with effector genes acquired from distinct mobile elements. In addi
 tion to their importance in prokaryotic biology and utility as genome edit
 ing tools\, the CRISPR-Cas systems shed light on general evolutionary prin
 ciples. Utilization of transposon-encoded nucleases as “guns for hire”
  in defense systems appears to be one of such principles. The apparent con
 tinuum of evolutionary processes from Darwinian selection among random var
 iants to the Lamarckian route of direct adaptation is another\, higher pla
 ne generalization.
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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