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. 2014 Jun 1;592(11):2319-41.
doi: 10.1113/jphysiol.2014.271130.

Physiology of the Read-Write Genome

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Physiology of the Read-Write Genome

James A Shapiro. J Physiol. .
Free PMC article


Discoveries in cytogenetics, molecular biology, and genomics have revealed that genome change is an active cell-mediated physiological process. This is distinctly at variance with the pre-DNA assumption that genetic changes arise accidentally and sporadically. The discovery that DNA changes arise as the result of regulated cell biochemistry means that the genome is best modelled as a read-write (RW) data storage system rather than a read-only memory (ROM). The evidence behind this change in thinking and a consideration of some of its implications are the subjects of this article. Specific points include the following: cells protect themselves from accidental genome change with proofreading and DNA damage repair systems; localized point mutations result from the action of specialized trans-lesion mutator DNA polymerases; cells can join broken chromosomes and generate genome rearrangements by non-homologous end-joining (NHEJ) processes in specialized subnuclear repair centres; cells have a broad variety of natural genetic engineering (NGE) functions for transporting, diversifying and reorganizing DNA sequences in ways that generate many classes of genomic novelties; natural genetic engineering functions are regulated and subject to activation by a range of challenging life history events; cells can target the action of natural genetic engineering functions to particular genome locations by a range of well-established molecular interactions, including protein binding with regulatory factors and linkage to transcription; and genome changes in cancer can usefully be considered as consequences of the loss of homeostatic control over natural genetic engineering functions.


Figure 1
Figure 1. Mechanism of class switch recombination that allows isotype switching in activated B cells
The boxes indicate exon cassettes and black diamonds indicate switch regions. Copied from Wikipedia and used according to Wikimedia Free Commons.

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