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Eugene Koonin on how CRISPR is leading to conceptual shifts in evolutionary biology

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Eugene Koonin/Konrad Foerstner

From Eugene Koonin at Immunoconcept:

Abstract: The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and even the general public thanks to the unprecedented success of the new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self vs non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids. CRISPR-Cas systems employ multiple mechanisms of self vs non-self discrimination but, as is the case with immune systems in general, are nevertheless costly because autoimmunity cannot be eliminated completely. In addition to the autoimmunity, the fitness cost of CRISPR-Cas systems appears to be determined by their inhibitory effect on horizontal gene transfer, curtailing evolutionary innovation. Hence the dynamic evolution of CRISPR-Cas loci that are frequently lost and (re)acquired by archaea and bacteria. Another fundamental biological feature of CRISPR-Cas is its intimate connection with programmed cell death and dormancy induction in microbes. In this and, possibly, other immune systems, active immune response appears to be coupled to a different form of defense, namely, “altruistic” shutdown of cellular functions resulting in protection of neighboring cells. Finally, analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements (MGE) to the origin of various components of CRISPR-Cas systems, Furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE. The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools.

Paper. (open access): Eugene Koonin, CRISPR: A New Principle of Genome Engineering Linked to Conceptual Shifts in Evolutionary Biology (National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA) https://www.ncbi.nlm.nih.gov/research/groups/koonin/

What is CRISPR?: “CRISPR technology is a simple yet powerful tool for editing genomes. It allows researchers to easily alter DNA sequences and modify gene function. Its many potential applications include correcting genetic defects, treating and preventing the spread of diseases and improving crops. However, its promise also raises ethical concerns.” – Aparna Vidyasagar, LiveScience

Philosopher of biology Paul Nelson writes to say,

Those of us who attended the Royal Society “extended synthesis” meeting in November 2016 were disappointed by the majority of talks presented there, most of which only fiddled at the margins of current neo-Darwinian theory, while never really challenging the core commitments of neo-Darwinism (e.g., undirected / random mutation). Well, Eugene Koonin should have been there in London, presenting on the thesis he articulates in this new MS, namely, that the CRISPR-Cas system may well overturn deep assumptions in evolutionary theory. Given that, Koonin’s case is relevant to design reasoning in biology as well.

See also: The second advent of the Royal Society’s evolution rethink last November?


NIH’s Eugene Koonin identifies key ways our approach to evolution has changed

Three New Cs for CRISPR: Collateral, Communicate, Cooperate Andrew Varble, Luciano A. Marraffini DOI:  10.1016/j.tig.2019.03.009
The core feature of CRISPR-Cas systems is the use of RNA-guided Cas nucleases that use a short RNA to locate and cleave complementary nucleic acids. Recent studies uncovered features that add substantial complexity to this central mechanism. Upon crRNA-guided recognition of complementary nucleic acids, many CRISPR-Cas systems also degrade nontarget RNA or ssDNA. The RNA-guided recognition of target RNA molecules triggers the production of cyclic oligoadenylate; a secondary messenger that activates the nonspecific degradation of RNA during type III CRISPR-Cas immunity. Many inhibitors of Cas nucleases have been found in phage genomes, which require the cooperative infection of viruses to gradually suppress the CRISPR-Cas immune response.
Clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated ( cas) genes provide protection against invading phages and plasmids in prokaryotes. Typically, short sequences are captured from the genome of the invader, integrated into the CRISPR locus, and transcribed into short RNAs that direct RNA-guided Cas nucleases to the nucleic acids of the invader for their degradation. Recent work in the field has revealed unexpected features of the CRISPR-Cas mechanism: (i) collateral, nonspecific, cleavage of host nucleic acids; (ii) secondary messengers that amplify the immune response; and (iii) immunosuppression of CRISPR targeting by phage-encoded inhibitors. Here, we review these new and exciting findings.
This is interesting:
The advances of genomics and metagenomics show that we are hardly aware of all or even the majority of such systems that exist in nature, particularly, in the microbial world. As potent as the CRISPR-Cas methodology is, there is no obvious reason to expect that it is the final achievement in genome editing and regulation technology. Beyond doubt, open-ended exploration of natural genome engineering mechanisms brings new possibilities. It remains to be seen whether these discoveries reveal fundamental new biology as it happened in the case of CRISPR-Cas.
Emphasis added. OLV
OLV(1): It's alright. The links work fine. It was my mistake. OLV
As a Creationist, I am no longer able to discuss evolution. The reason is this: Nobody can tell me what Evolution is. For about 150 years we've been taught that Lamarckian Evolution had been proved false, and belonged in the dustbin of failed Science, along with Caloric Theory, Phlogiston, Phrenology, and Luminiferous Ether. But today, as Dr Koonin's abstract shows, Lamarckian Evolution has been unproved false, and is back as Settled Science, where it plays a crucial role, whose scope, mechanisms and significance are unclear. And, surprise surprise, need further funding. chris haynes
the links don't seem to work for me https://upload.immuconcept.org/ OLV

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