The genome of the PUFFER FISH offers a point of comparison by which we can measure the efficiency and efficacy of our own. Illustration by Alison Schroeer.
When I mention the Japanese puffer fish, or fugu, to friends and students who are even slightly pop-culture savvy, I get a predictable response: That’s the fish that almost killed Homer Simpson! The fugu is an actual fish, and a beautiful little advanced bony one. Among its claims to fame is that it protects itself from being eaten by secreting a potent neurotoxin called tetrodotoxin that blocks nerve impulses and can kill a person in a high enough dose. That’s part of the reason humans eat it, though: If carefully prepared and not eaten in excess, it can provide a peculiar tingle to the lips—and the thrill of a little danger. In the well-known episode of The Simpsons, Homer discovers the joys of sushi, overindulges in poorly prepared fugu, thinks he has only a day to live, and typical sitcom hijinks ensue (ruined slightly for us science geeks, who know that fugu poisoning leads to rapid paralysis, which would tend to interfere with hijinks).
Fugu has another property of greater interest to evolutionary and developmental biologists, molecular biologists, and geneticists, though: It has an unusual genome. Through genomes, biology organizes genetic material into different forms of life; what we often find is that the real surprises are deep, hidden, and require a delicate sense of appreciation. In order to explain what’s unusual about the fugu’s genome, a comparison with our own human genome is in order.
One of the clear results of the Human Genome Project is that our genomes are incredibly junky: Our DNA contains approximately 3.2 billion base pairs, about the amount of information that can be stored on a single CD, but only about 5 percent of that information plays a significant role in constructing the human form. Our human CD contains, in effect, the equivalent of one really good, but short, pop song, with the rest of the tracks being staticky hisses, noise, and repetitions of the same short phrase, over and over again.
Now, you might want to argue that we simply lack the sophistication to appreciate the other 95 percent. But we actually do know what the function of a significant fraction of the junk is, and that it’s not to our benefit.
One element common to both human and fugu is a DNA sequence called LINE, short for Long Interspersed Element. LINE, itself a gene about 6,000 base pairs long, codes for an enzyme called a reverse transcriptase. The key here is that it recognizes its own RNA sequence, and repeatedly inserts copies of itself into our genome. LINEs seem to be relics of the “copying machinery” of old viral infections wherein a virus would embed a portion of itself into our genome, not enough to propagate the full, infectious virus, but enough to continue copying itself. It is a classic example of a selfish gene: It has no purpose but to do only that, without benefit to us.
Another repeated element in the genome is a shorter sequence called a SINE, or Short Interspersed Element. These are only a few hundred base pairs long and don’t actually do anything, as they don’t code for a functional protein. They do contain regulatory elements that trigger the cellular machinery to make RNA from them, however, and this SINE RNA has a selfishly advantageous property: It is recognized by the LINE reverse transcriptase, which can obligingly insert duplicate SINEs back into the genome.
There are overwhelming numbers of these repeated elements in the human genome: about a half-million copies of LINEs and about a million copies of SINEs, taking up about 45 percent of the total DNA. Note also that most of these copies are actually broken, since the few functioning copies of the LINE enzyme aren’t particularly efficient and often insert only fractional copies. In addition, we have about 20,000 genes taking up 5 percent of the genome that do all the essential work of the organism—making liver enzymes and hemoglobin and the keratin of our skin and regulating the patterns of gene expression and so forth—so you can easily get the impression that the primary purpose of human cells is to maintain a cozy environment for the proliferation of junk DNA. This is more than mere junk, though: The perfect word for it is kipple, the term coined by science fiction author P.K. Dick for unwanted junk that tends to reproduce itself and grow.
It is disconcerting for us to discover that our cells aren’t well-honed, efficient machines dedicated to making just the important stuff of us, but rather are carting around massive quantities of useless bric-a-brac and debris. Which brings us back to the fugu. Its genome is a tiny 365 million bases, one-eighth the size of the human genome, and the fugu genes take up a full third of that sequence (rather than 5 percent), while the repetitive DNA has been reduced to a sixth of the total (rather than 45 percent). Yet fugu aren’t missing anything, and are as sophisticated and complex on the cellular, tissue, and organismal level as other vertebrates. What’s the source of the difference?
While the molecular evidence suggests that fugu aren’t immune to LINEs and SINEs and that they are infected with more diverse reverse transcriptases than we are, fugu have evolved mechanisms for dealing with these selfish segments of DNA that go beyond merely silencing them. They also actively excise them from the genome. This probably was not the result of an abrupt process. It may simply be that the repetitive elements are deleted at a slightly higher rate than that at which they can add themselves to the genome, leading to a gradual paring away of the junk. In the world of genomic housekeeping, the puffer fish is a neatnik who keeps the trash under control, while the rest of us are pack rats hoarding junk DNA.
There’s a lot of thought these days going into trying to figure out some adaptive reason for such a sorry state of affairs. None of it is particularly convincing. We’d be better off reconciling ourselves to the notion that much of evolution is random, and that nothing prevents nonfunctional complexity from simply accumulating. As evolutionary biologist T. Ryan Gregory puts it, any functional explanation for all that junk has to take into account why an onion would need so much more of it than we do. He calls it the onion test.
Perhaps an important lesson from the differences is that efforts to use quantitative measures of complexity to justify a ladder of life, with some species held as “more evolved” than others, are an exercise in futility. Bony fish like fugu and land-dwelling tetrapods like humans diverged over 450 million years ago, and what we’ve both been doing is busily accumulating differences, not superiority in one lineage or another. Consider that when you’re cautiously nibbling at your carefully prepared sushi. The fish you consume are as wonderful and complex as you are, and may even have surpassed you, when it comes to their genome, in their degree of elegance.
Originally published May 30, 2008