Eugene - Edmond J. Safra Bioinformatics

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You are cordially invited to a talk of the Edmond J. Safra Bioinformatics Program

Distinguished Speaker Series .

The speaker is Prof. Eugene V. Koonin, Senior Investigator, National Center for

Biotechnology Information, NIH, Bethesda, Maryland, USA.

Title : CRISPR-Cas: an Adaptive Immunity System in Archaea and Bacteria, a paragon of Lamarckian Evolution and a General Model for Evolution of

Environmental Sensors

Time : Monday, 26 March 2012, at 11:00 (refreshments from 10:45)

Place : Schreiber 006

Abstract: All organisms face environmental changes that are only partially predictable. A longstanding evolutionary question is: when does organismal fitness increases through maintenance of costly sensors which directly optimize host phenotypes to match changing environments? A recently discovered immune sensor in prokaryotes offers a unique model system to study the conditions under which

‘Lamarckian’, sensor-based evolution occurs. Known as Clustered Regularly

Interspaced Short Palindromic Repeats and CRISPR-associated genes (CRISPR-

Cas), this system serially incorporates short fragments from viral or plasmid DNA, and employs the newly acquired sequences to specifically target cognate DNA in subsequent viral and plasmid invasions. I present the results of a comprehensive comparative genomic analysis of the CRISPR-Cas system and a simple evolutionary scenario leading to the currently observed diversity of the CRISPR-Cas loci. Over

90% of archaea but less than 50% of bacteria possess CRISPR-Cas. The archaealbacterial dichotomy in CRISPR-Cas prevalence appears to be is environmentally driven: whether Archaea or Bacteria, hyperthermophiles possess CRISPR-Cas far more frequently than mesophiles. A mathematical model was developed to capture the conditions under which hosts maintain CRISPR-Cas. Implementing mutation, selection and drift in digital organisms, the model continually weighs the benefits of

CRISPR-mediated immunity against the fitness cost of maintaining CRISPR-Cas systems. Across thousands of simulations in multi-dimensional parameter space, we find that there is a threshold of the viral mutation rate, above which the hosts cannot keep CRISPR-Cas systems. Irrespective of CRISPR spacer addition rate, extremely rapid viral mutation renders CRISPR-Cas ineffectual, driving the loss of CRISPR-Cas loci. Given that mutations are especially deleterious to viral fitness in extreme environments, our results offer a simple, testable hypothesis

—constrained viral diversity —to explain why extremophiles disproportionately possess CRISPR. The results suggest a fundamental limit on the adaptability of organisms that rely on sensors to respond to environmental stochasticity.

Host: Dr. Uri Gophna, microevol@gmail.com

, Life Sciences Faculty.

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