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Genome Analysis of Unicellular Organism Reveals Frequent, Massive Reshuffling

Tuesday, September 9, 2014

A recent publication from senior author Laura Landweber at Princeton University offers a remarkable and unexpected look at sweeping genomic rearrangements in a unicellular organism.

The Architecture of a Scrambled Genome Reveals Massive Levels of Genomic Rearrangement during Development,” published in Cell, comes from lead authors Xiao Chen and John Bracht as well as other collaborators from Princeton, the Icahn School of Medicine at Mount Sinai, Benaroya Research Institute, and other institutions.

The project focused on Oxytricha trifallax, a single-celled eukaryote that lives in ponds. Despite its unicellular simplicity, the organism has an extensive ability to scramble and rearrange its genome as needed. During normal existence, Oxytricha’s genome is stored in more than 3,500 deliberately fragmented genes. Prior to mating, the organism deletes noncoding portions of the genome, breaks up what’s left into some 225,000 pieces, and shuffles and assembles those into a completely new somatic genome.

Oxytricha was already known to be unusual for its extra-large cell size (about 10 times the size of a human cell), double nucleus, and a reported repertoire of 16,000 chromosomes. Now, scientists anticipate using it as a model for elucidating how chromosomes break up and rejoin in more complex organisms, such as during the onset of cancer.

In their genome analysis, the authors found that Oxytricha’s second nucleus is critical to the genomic rearrangement process. While one nucleus houses the organism’s active DNA, the second nucleus serves as a massive archive from which Oxytricha selects genetic material to exchange with its mate. The organism will stitch together some 225,000 genomic regions for this process, the paper reports. The procedure is governed by an “elaborate, RNA-mediated pathway [that] eliminates noncoding DNA sequences that interrupt gene loci and reorganizes the remaining fragments by inversions and permutations to produce functional genes,” the authors note.

For this effort, the scientists used Single Molecule, Real-Time (SMRT®) Sequencing to analyze the germline genome and compared it to the somatic genome. The authors state, “Long PacBio® reads allowed us to successfully assemble as many as 16 complete TBE transposons on a single MIC contig (three TBE1, seven TBE2, and six TBE3), demonstrating the power of this approach to resolve repetitive regions.”

In an interview, Landweber said, “It’s one of nature’s early attempts to become more complex despite staying small in the sense of being unicellular. There are other examples of genomic jigsaw puzzles, but this one is a leader in terms of complexity.”  See a more detailed review of the paper by Princeton University.

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