Saturday, May 16, 2009

About those Oxytricha transposases

Ciliate genomics is nifty. Ciliates are little one-celled organisms. You're probably familiar with the ciliate Paramecium, ubiquitous in high school and college biology lab exercises. Unlike most familiar eukaryotes, paramecia have two nuclei in each cell, a large and easily recognizable macronucleus and a much tinier micronucleus. The macronucleus is transcriptionally active, meaning that it's the one that carries on the day-to-day activities in the cell. The micronucleus is used in sexual conjugation. After sex, the existing macronucleus degrades, and a new one is synthesized from the micronucleus.

Oxytricha is a ciliate like Paramecium, though they are not particularly similar (pictures here). Like Paramecium, Oxytricha has a transcriptionally-active macronucleus and a reproductive micronucleus. The macronucleus is replaced after each sexual conjugation. Here's where it starts to get confusing: When you actually count up the amount of DNA in the Oxytricha, the macronucleus (at 50 Mb) turns out to be much tinier than the micronucleus (1 Gb). They look different under the microscope because the macronucleus is all unwound for transcription, while the larger micronucleus is neatly and tightly packed away. When reconstructing the macronucleus from the micronucleus, 95% of the DNA in the micronucleus is processed out and removed. So the active genome needed to carry on normal cellular functions is just 5% of the DNA in the reproductive genome of the micronucleus.

Now it gets even stranger: In a new paper in the latest Science, Nowacki et al. show that transposases are required to carry out proper processing of the micronuclear genome to generate the much smaller macronuclear genome. Transposases are found in transposons, which are DNA sequences that are capable of moving themselves around chromosomes. Some researchers have considered transposons to be genomic parasites, a concept called "selfish DNA." With this new evidence from Oxytricha, Nowacki et al. conclude,
These transposons might not merely be parasitic invaders that reduce host fitness or have little phenotypic effect but instead mutualists directly contributing a useful function for the organism, such as genomic DNA processing.

Functionalists (i.e. those who think that selfish DNA must have a function) should be very excited by this paper, but I think we need to keep some things in mind. First, this seems to be a unique system. These important transposons in ciliates do not tell us what transposons are doing in plants or even people. Second, in a sense, these ciliate transposons also don't tell us much about what they are doing in the ciliate genomes. Why have such a convoluted system of reproduction? What's wrong with the fusing of gametes? Why go through this weird genome processing in the first place?

I don't mean to diminish the importance of Nowacki et al.'s work, because it's really amazing stuff. I also think that it's not a slam dunk for understanding the nature, meaning, and purpose of transposons in general. Oxytricha transposons are too isolated and odd to offer much in the way of broader understandings of transposons. I know transposons exist for a reason (functional or not, I don't know). Transposons are found in just about everything, they compose large fractions of many eukaryotic genomes, and the shared transposons in humans and chimps indicate that they were designed to be there. I don't think God just designs willy-nilly. Transposons are there for a reason. We just have to find out what that reason is.

Nowacki et al. 2009. A functional role for transposases in a large eukaryotic genome. Science 324:935-938.