How nature builds a genome from 225,000 pieces

10 October 2014

Laura Landweber
Department of Ecology and Evolutionary Biology
Princeton University


New roles for noncoding RNAs keep emerging, often in unexpected places. My lab uses a noncanonical model system, the ciliate Oxytricha, to study RNA-guided genome programming. Oxytricha is unique in possessing two nuclear genomes, with massive DNA rearrangements carving out a somatic nucleus from a spare germline nucleus during post-zygotic development. This process of genome decryption jettisons nearly all noncoding DNA, including transposons, from the somatic genome and rearranges over 225,000 remaining short DNA segments to construct functional genes out of scrambled precursors [1]. The mature, somatic genome contains over 16,000 tiny "nanochromosomes" that typically encode just a single protein or RNA [2].

Noncoding RNAs play diverse roles throughout this entire process (for a recent review, see [3]). Maternally-inherited, long, non-coding RNAs provide templates for both genome remodeling and RNA-guided DNA repair, while also regulating gene dosage and chromosome copy number. Small RNAs in the form of 27nt piRNAs provide the critical information to mark and protect the fraction of the genome that gets retained [4]. Together, Oxytricha's elaborate epigenome, crafted through complex interacting networks of long and small non-coding RNAs, encapsulates an RNA-driven world within 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, and even to reconstruct chromosomes.


  1. X Chen, J R Bracht, A D Goldman, E Dolzhenko, D M Clay, E C Swart, D H Perlman, T G Doak, A Stuart, C T Amemiya, R P Sebra, L F Landweber, "The architecture of a scrambled genome reveals massive levels of genomic rearrangement during development", Cell 158:1187-98 2014. PubMed Paper
  2. E C Swart, J R Bracht, V Magrini, P Minx, X Chen, Y Zhou, J S Khurana, A D Goldman, M Nowacki, K Schotanus, S Jung, R S Fulton, A Ly, S McGrath, K Haub, J L Wiggins, D Storton, J C Matese, L Parsons, W J Chang, M S Bowen, N A Stover, T A Jones, S R Eddy, G A Herrick, T G Doak, R K Wilson, E R Mardis, L F Landweber, "The Oxytricha trifallax macronuclear genome: a complex eukaryotic genome with 16,000 tiny chromosomes.", PLoS Biol 11:e1001473 2013. Paper
  3. J R Bracht, W Fang, A D Goldman, E Dolzhenko, E M Stein, L F Landweber, "Genomes on the edge: programmed genome instability in ciliates", Cell 152:406-16 2013. Paper
  4. W Fang, X Wang, J R Bracht, M Nowacki, L F Landweber, "Piwi-interacting RNAs protect DNA against loss during Oxytricha genome rearrangement", Cell 151:1243-55 2012. Paper

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