Origins Forum - "RNA-Mediated Epigenetics and Extreme Genome Architectures in the Ciliate Oxytricha"


Wednesday, October 16, 2013, 4:00pm to 5:00pm


Geological Museum, Haller Hall (Room 102), 24 Oxford Street

Laura Landweber  
Dept. of Ecology & Evolutionary Biology
Princeton University

The unicellular eukaryote Oxytricha trifallax has an extremely dynamic pair of genomes, with massive DNA rearrangements producing a highly fragmented, somatic genome from a germline genome roughly twenty times its sequence complexity. During development, Oxytricha eliminates nearly all its noncoding DNA, including all its transposons, and rearranges the ~225,000 remaining DNA pieces to produce functional genes. In the precursor, germline genome, the scattered segments of different genes often interweave with each other, frequently overlap, and sometimes combinatorially assemble into multiple, distinct loci. The whole process produces a somatic genome of over 16,000 "nanochromosomes" that range from 469 to 66,000 base-pairs long and typically encode single genes, though a small portion contain up to 8 genes that can be processed into different combinations (Swart et al. 2013 PLoS Biology 11:e1001473). Furthermore, RNA, normally thought of as a conduit in gene expression, has novel modes of action during this radical process of genome rearrangement. Maternally-inherited long, non-coding RNAs (lncRNAs) provide 3 layers of continuity across generations, including serving as templates for both genome remodeling and DNA repair (Nowacki et al. 2008 Nature 451:153-8) and regulators of gene dosage and chromosome copy number (Nowacki et al. 2010 PNAS 107:22140-4). These illustrate the ability of lncRNAs to transmit somatic changes to the next generation. In addition, small RNAs provide the critical information to mark and protect which ~225,000 pieces of the genome to retain (Fang et al. 2012 Cell 151:1243-55). Together, Oxytricha's elaborate epigenome, assembled through interacting networks of long and short non-coding RNAs supplied from the previous generation, encapsulates an RNA-driven world in a modern cell. The mechanism for all of these dynamic actions bypasses the traditional, modern pathway of inheritance via DNA, hinting at the power of RNA molecules to sculpt genomic information out of smaller pieces. It illustrates that gene linkage is not necessary and that tiny fragments of genetic information can assemble to produce miniature-sized chromosomes with full range of modern function.

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