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Review How life changes itself: The Read-Write (RW) genome James A. Shapiro Dept. of Biochemistry and Molecular Biology, University of Chicago, GCIS W123B, 979 E. 57th Street, Chicago, IL 60637, USA Received 27 June 2013; accepted 2 July 2013 Available online 8 July 2013 Communicated by M. Frank-Kamenetskii Abstract The genome has traditionally been treated as a Read-Only Memory (ROM) subject to change by copying errors and accidents. In this review, I propose that we need to change that perspective and understand the genome as an intricately formatted Read–Write (RW) data storage system constantly subject to cellular modifications and inscriptions. Cells operate under changing conditions and are continually modifying themselves by genome inscriptions. These inscriptions occur over three distinct time-scales (cell reproduction, multicellular development and evolutionary change) and involve a variety of different processes at each time scale (forming nucleoprotein complexes, epigenetic formatting and changes in DNA sequence structure). Research dating back to the 1930s has shown that genetic change is the result of cell-mediated processes, not simply accidents or damage to the DNA. This cell-active view of genome change applies to all scales of DNA sequence variation, from point mutations to large-scale genome rearrangements and whole genome duplications (WGDs). This conceptual change to active cell inscriptions controlling RW genome functions has profound implications for all areas of the life sciences. © 2013 Elsevier B.V. All rights reserved. Keywords: Epigenetics; Natural genetic engineering (NGE); Mobile genetic elements (MGEs); Genome inscriptions

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