You Have 46 Chromosomes. This Pond Creature Has 15,600
Remember when encyclopaedias were books, and not just websites? You’d have a shelf full of information, packaged into entries, and then into separate volumes. Your genome is organised in a similar way. Your DNA is packaged into large volumes called chromosomes. There are 23 pairs of them, each of which contains a long string of genes. And just as encyclopaedia books are bound in sturdy covers to prevent the pages within from fraying, so too are your chromosomes capped by protective structures called telomeres.
That’s basically how it works in any animal or plant or fungus. The number of chromosomes might vary a lot—fruit flies have 8 while dogs have 78—but the basic organisation is the same.
But there’s a pond-dwelling creature called Oxytricha trifallax whose DNA is organised in a very… different… way. A team of US scientists has sequenced its genome for the first time and discovered genetic chaos. It’s like someone has taken the encyclopaedias, ripped out all the individual pages, torn some of them, photocopied everything dozens of times, and stuffed the whole lot in a gigantic messy drawer.
Oxytricha trifallax is neither animal nor plant, but protist –part of the kingdoms of life that include amoebas and algae. Composed of just a single cell, it never gets bigger than a quarter of a millimetre in length. It swims around ponds and puddles in search of other microbes to consume, and moves by beating small hairs called cilia. These hairs give it and its relatives their group name—the ciliates.
Within its cell, Oxytricha contains two nuclei, which enclose its DNA. One of these—the micronucleus— contains the complete edition of Oxytricha’s genome, just like the single nucleus within our own cells. That’s the tidy encyclopaedia shelf. But while the material in our nucleus must be constantly decoded and transcribed so that we can live, Oxytricha’s micronucleus is largely inactive. The encyclopaedia’s are barely read.
Instead, it relies on a second structure called the macronucleus. That’s the messy drawer. All of the DNA in the micronucleus is copied thousands of times over, and shunted into the macronucleus. In the process, it is broken up at tens of thousands of places, rearranged, and pruned. What’s left is a collection of thousands of “nanochromosomes” that contain all the information Oxytricha needs to survive. This is the stuff that gets decoded and transcribed, used and reused while the originals gather dust.
Sequencing this almighty mess must have been a devilish task, but Etienne Swart from Princeton University rose to the challenge. Leading a team of US and Swiss scientists, he has sequenced Oxytricha’s complete macronuclear genome. Modern sequencing works by breaking genomes into small fragments, sequencing these, and assembling everything together. The DNA in Oxytricha’s macronucleus is already fragmented and extremely repetitive, make it hard to capture everything and assemble it into a coherent whole. Then again, almost three-quarters of the fragments were already complete chromosomes.
The team found around 15,600 of these nanochromosomes. On average, each is around 3,200 DNA ‘letters’ long, and around 80 percent of them contain just a single gene.
As if that wasn’t complicated enough, the genome is duplicated so extensively that there are around 2,000 copies of each nanochromosome. And around one in ten of them are broken up into even smaller fragments. So, different copies of the same nanochromosomes might just contain a small passage from the full page of information.
Our 46 chromosomes are capped by protective structures called telomeres that stop DNA from fraying, rather like the plastic tags on the end of shoelaces. All of Oxytricha’s nanochromosomes have their own telomeres, so each individual has tens of millions of these protective caps. It has, in Swart’s words, an “inordinate fondness for telomeres”. It’s like every page in its messy drawer is hard-bound.
As the contents of the micronucleus are copied into the macronucleus, anything that doesn’t contain instructions for making proteins—the so-called “non-coding DNA”—is ruthlessly pruned. Around 96 percent of the genome is jettisoned in this way. The remainder—the nanochromosomes—are a small fraction of the full genome, but they contain all the genes that Oxytricha needs for day-to-day existence. The only things missing are a smattering of genes that the creature needs to reproduce.
This isn’t just an academic exercise, targeted at an (admittedly cool) creature. Ciliates have a long history of teaching us about our own genomes. Another of them—Tetrahymena thermophila—taught us about the existence of telomeres in the first place, and these structures are now through to play critical roles in ageing, cancer and other aspects of our lives. Tetrahymena also helped to show that RNA—a genetic molecule that’s related to DNA—can act as an enzyme. That’s crucial to modern theories about the origin of life itself. (And its genome was fully sequenced back in 2006, by the inimitable Jon Eisen)
Meanwhile, Oxytricha, with its bonanza of telomeres, helped scientists to identify the proteins that stick to these caps and help to create, maintain and control them. Perhaps its bizarre genome will tell us even more about how DNA is rearranged and copied—something that happens in our genome to a less dramatic (but still important) extent.
Reference: Swart EC, Bracht JR, Magrini V, Minx P, Chen X, et al. (2013) The Oxytricha trifallax Macronuclear Genome: A Complex Eukaryotic Genome with 16,000 Tiny Chromosomes. PLoS Biol 11(1): e1001473.
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