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Genes Smash! An Oxytricha trifallax story

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In DNA mutation is often a bad thing. It’s sort of like building a car, there are far more wrong ways to one together than there are right ways. Still, mutation happens often which brings with it good (and more often bad) things. Usually mutation is spontaneous, it has no real rhyme or reason (in a broad sense) and while it brings things like cancers, it also can bring amazingly beneficial traits too. Maybe this is why a pond-dwelling, single-celled organism called Oxytricha trifallax is so keen on mixing things up. By that I mean it has the remarkable ability to break its own DNA into nearly a quarter-million pieces and rapidly reassemble those pieces when it’s time to mate.

The organism internally stores its genome as thousands of scrambled, encrypted gene pieces. Upon mating with another of its kind, the organism rummages through these jumbled genes and DNA segments to piece together more than 225,000 tiny strands of DNA. Keep in mind this is all far more complex than our own genome (Oxytricha has roughly 16,000 chromosomes to our measly 46). Maybe that is why this all takes about 60 hours to accomplish (which is pretty quick when you think about it).

The organism’s ability to take apart and quickly reassemble its own genes is unusually elaborate for any form of life, explained senior author Laura Landweber, a Princeton professor of ecology and evolutionary biology. That such intricacy exists in a seemingly simple organism accentuates the “true diversity of life on our planet,” as she put it.

“It’s one of nature’s early attempts to become more complex despite staying small in the sense of being unicellular,” Landweber said. “There are other examples of genomic jigsaw puzzles, but this one is a leader in terms of complexity. People might think that pond-dwelling organisms would be simple, but this shows how complex life can be, that it can reassemble all the building blocks of chromosomes.”

From a practical standpoint, Oxytricha is a model organism that could provide a template for understanding how chromosomes in more complex animals such as humans break apart and reassemble, as can happen (as I mentioned earlier) during the onset of cancer. But while chromosome dynamics in cancer cells can be unpredictable and chaotic, Oxytricha presents an orderly step-by-step model of chromosome reconstruction, a sort of blueprint for how things should look (at least in this case).

“It’s basically bad when human chromosomes break apart and reassemble in a different order,” Landweber said. “The process in Oxytricha recruits some of the same biological mechanisms that normally protect chromosomes from falling apart and uses them to do something creative and constructive instead.”

The rampant and diligently orchestrated genome rearrangements that take place in this organism demonstrate a unique layer of complexity for scientists to consider when it comes to studying an organism’s genetics.

“This work illustrates in an impressive way that the genetic information of an organism can undergo substantial change before it is actually used for building the components of a living cell,” said Burger, who is familiar with the work but had no role in it.

“Therefore, inferring an organism’s make-up from the genome sequence alone can be a daunting task and maybe even impossible in certain instances,” Burger said. “A few cases of minor rearrangements have been described in earlier work, but these are dilettantes compared to [this] system.”

The work is really extremely comprehensive as to the experimental techniques employed and analyses performed. The project is one of the first complex genomes to be sequenced using Pacific Biosciences (PacBio) technology that reads long, single molecules.

Oxytricha already stands apart from other microorganisms, it is a large cell, about 10 times the size of a typical human cell. The organism also contains two nuclei whereas most single-celled organisms contain just one. A cell’s nucleus regulates internal activity and, typically, contains the cell’s DNA as well as the genes that are passed along during reproduction.

An individual Oxytricha cell, however, keeps its active DNA in one working nucleus and uses the second to store an archive of the genetic material it will pass along to the next generation, Landweber said. The genome of this second nucleus — known as the germ-line nucleus — undergoes the dismantling and reconstruction to produce a new working nucleus in the offspring.

Oxytricha uses sex solely to exchange DNA rather than to reproduce, Landweber said — like plant cuttings, new Oxytricha populations spawn from a single organism. During sex, two organisms fuse together to share half of their genetic information. The object is for each cell to replace aging genes with new genes and DNA parts from its partner. Together, both cells construct new working nuclei with a fresh set of chromosomes. This rejuvenates them and diversifies their genetic material (which is good for the organism).

“It’s kind of like science fiction — they stop aging by trading in their old parts,” she said.

It’s during this process that the scrambled genes in the germ-line nuclei are sorted through to locate the roughly 225,000 small DNA segments that each mate uses to reconstruct its rejuvenated chromosomes. Previous work has shown that millions of noncoding RNA molecules from the previous generation direct this undertaking by marking and sorting the DNA pieces in the correct order.

Also impressive is the massive scale of Oxytricha‘s genome, as I mentioned before it has roughly  16,000 chromosomes. Keep in mind that most of Oxytricha‘s chromosomes contain just a single gene, but even those genes can get hefty. A single Oxytricha gene can be built up from anywhere between one to 245 separate pieces of DNA.

The exceptional genetics of Oxytricha protect its DNA, so that mainly healthy material is passed along during reproduction. It’s no wonder then that the organism can be found worldwide munching on algae.

“Their successful distribution across the globe has something to do with their ability to protect their DNA through a novel method of encryption, then rapidly assemble and transmit robust genes across generations,” Landweber said.

I don’t know about you, but that is one hardcore organism. It’s funny that a (relatively) simple single cell organism could potentially teach us so much about how genes work. All because of it’s amazing ability to rearrange them just right. Now, if only we could do that, think of the possibilities! Need some help imagining them? This post would be a very interesting place to start, it also happens to be one of my favorite genetics blogs.

Sources
Chen X, Bracht JR, Goldman AD, Dolzhenko E, Clay DM, Swart EC, Perlman DH, Doak TG, Stuart A, Amemiya CT, Sebra RP, & Landweber LF (2014). The Architecture of a Scrambled Genome Reveals Massive Levels of Genomic Rearrangement during Development. Cell, 158 (5), 1187-98 PMID: 25171416

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4 responses

  1. What a completely bizarre organism! I’ll be interested to see what this means for chromosome shattering in humans…they must have a very unrepetitive genome to be able to reassemble it correctly from non-coding RNA.
    So the DNA it stores…do you think that’s one copy of each chromosome? Interesting. I wonder how it decides which one will remain active

    March 7, 2015 at 5:34 am

    • Honestly, you might be more qualified to answer that one then I would. It sounds like it is a copy of each from the wording in the paper. I agree that it’s amazing to think that it can spontaneously shatter its chromosomes and somehow reassemble them in a working order (seemingly) every time. Personally, I would think it uses some sort of DNA methylation to mark and categorize everything in an amazing show of the power in epigenetics. But then again I’m an armchair geneticist, so you probably shouldn’t listen to me. 🙂

      March 7, 2015 at 11:43 am

      • That’s an interesting thought – could be! Sadly my genetics knowledge is very sapiocentric so your guess is really as good as mine here. Thanks for the shout-out by the way!

        March 9, 2015 at 5:30 am

      • Fair enough, well we can wonder together then! As far as the shout out, of course I love your blog.You come up with some of the most creative genetics posts I’ve read. More people need to find it.

        March 9, 2015 at 6:31 pm

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