23 April 2011

Alu need to know about parasitic DNA: Introduction to Alu elements

Defenders of intelligent design theory often dwell on the topic of "junk DNA," which has been molded into a masterpiece of folk science. The ID approach to "junk DNA" involves a fictional story about "Darwinism" discouraging its study, and a contorted and simplistic picture of a "debate" about whether "junk DNA" has "function." The fictional story is ubiquitous despite being repeatedly debunked. But the picture of an ongoing "debate" about "function" is harder to sort out. Like most propaganda, that picture contains enough truth to sound plausible. (Browse my "Junk DNA" posts, and work by Ryan Gregory and Larry Moran, for more information on errors and folk science associated with these topics.)

There is, in fact, some scientific disagreement about functions of various elements in genomes, but it's not the crude standoff that ID apologists depict, and it has very little to do with "Darwinism." The debate, if we must call it that, is about at least two matters: 1) the extent to which certain genomic elements contribute to normal function or development of organisms; and 2) the means by which we might determine this. The debate is not about whether non-coding DNA can have function, or even about whether some segments of non-coding DNA do have function. That debate was invented by anti-evolution propagandists.

Now, one thing that is often overlooked in discussions of non-coding DNA is the fact that we know quite a bit about most of it. In other words, it's not the case that scientists look at the human genome and say, "Oh dear, what is all that extra DNA?" Instead, they look at the human genome and say, "Wow, look at all those mobile elements." While this is not to say that there aren't a lot of things in genomes that we don't yet understand, it's important to note that a substantial fraction of the human genome is made up of things we understand pretty well: pieces of DNA that, virus-like, are capable of copying themselves and/or moving to new locations in the genome. More than 40% of the human genome is composed of these mobile elements.

Before we talk about "functions" of these elements, we should face the magnitude of their presence. Also known collectively as genome-wide repeats, they fall into four categories: SINEs, LINEs, LTR elements, and DNA transposons. Consider the SINEs (short interspersed nuclear elements), just one of the four families of mobile elements. Together, SINEs make up a staggering 13% of the human genome. In raw numbers, this is 420 megabases out of 3.2 gigabases of DNA sequence in the human genome. (A base is one "letter" in the genetic code.) Those 420 million letters of code are accounted for by about 1.6 million individual elements. And 1.1 million of those SINEs are of a very interesting type: they are Alu elements.

Alu elements are the most abundant mobile genetic elements in the human genome. They are primate-specific, meaning that they are only found in monkeys and apes and their close relatives. It would take a separate post to fully discuss their characteristics and theories regarding their origins, and I'll come back to that soon. For now, let's start here: an Alu element is a piece of DNA that resembles a virus in that it is mobile and relies on the cell's machinery for its activity. Alu elements are retroelements, meaning that they first copy themselves into RNA in order to "jump" elsewhere in the genome.

Now, how do we know this about Alu elements? Surely we haven't examined each of the 1.1 million Alu elements in the human genome, much less the zillions of them in other primates. No, but here are the two main sources of evidence that Alu elements are mobile genetic elements.

1. We've seen them jump, and we know a bit about how they do it. Simply put, Alu elements are known to move, and they move by using known mechanisms. In fact, biologists have estimated the likelihood that a new "jumping" event will occur in a newly-conceived human embryo to be about 5%, meaning that roughly one in twenty persons are born with a new Alu element insertion somewhere in her/his genome. The process by which Alu elements move is very similar to the processes used by other mobile elements.

2. They're highly conserved, meaning that one Alu element looks a whole lot like all the others. (There are five or six subtypes of Alu elements; the similarity is even more pronounced within those groups.) So we're not talking about a vague category of things that look sort of like a jumping gene. We're talking about a family of DNA elements with very specific features. Remember that they're also called "repeats," because even in the early days of genomic analysis (before we had the actual sequences of whole genomes) biologists knew that huge stretches of the human genome were made of chunks of DNA that were highly similar -- often identical -- and repeated over and over and over.

Taken together, then, in the Alu elements we have a huge family of closely-related DNA elements with structural features that are known to mediate movement within the genome. If all that sounds a little too technical, don't worry; what matters is that you grasp the basic notion (human genomes harbor so-called "jumping genes" that can move about within those genomes) and its magnitude (Alu elements are just one type of mobile element, and they alone make up more than 10% of the human genome).

So, do these things have a "function"? That's a tricky question. (Just the kind of question preferred by ID propagandists.) Alu elements and their kin are currently viewed by biologists as parasites, and if you know anything about parasitism then you know it's a bit too simplistic to ask whether a parasite is "good" or "bad" for its host. In many parasitic relationships, the host organism incurs some cost (or risk) by hosting the parasite, but also enjoys some benefit. You might think of the bacteria in your gut in this way; they're good to have around, but they can cause problems if they get out of bounds. It's like they've been domesticated: they're still potentially harmful, but if kept in control they're useful. Or at least, if they obey the rules, they're not too big a burden.

Considered in this way, Alu elements make sense. They can be useful. For one thing, their sheer bulk enlarges the genome, and genome size affects things like cell size. Alu elements can introduce new genetic diversity into a species, far more quickly than other kinds of mutation, and so they can be drivers of evolutionary change, by altering the genetic landscape literally overnight. Some Alu elements are known to influence the expression of genes (i.e., when those genes are on or off). And, notably, Alu elements can sometimes be converted into useful genes. In other words, like conventional biological parasites, they can be good to have around.

But, like conventional biological parasites, they can be dangerous. Alu elements can destroy critical genes by hopping into them. (The Alu element is about 300 DNA "letters" in length, and if those letters are added to the protein-coding part of a gene, the nearly-certain outcome is the conversion of the gene to gibberish.) Such events are known to underlie instances of devastating human genetic diseases. Because the Alu elements are so numerous and because the various types all look almost completely alike, they foster damaging interactions between parts of the genome and thereby facilitate large-scale genetic damage. And so humans (and other animals) pay a significant price for hosting mobile genetic elements, and the risks are exactly what we would expect from "jumping genes" that move without regard to the potential harm their relocations can cause.

Those facts alone should lead us to predict that humans (and other animals) would employ defenses against these parasites, if not to eradicate them then at least to keep them from overrunning the place. And these facts should make readers of most ID writing on this topic think a lot differently about ID claims. For one thing, we should be suspicious of any argument tackling the strawman of whether or not Alu elements are "functional elements" as opposed to "junk DNA."

But look again at the risks that I discussed. I mentioned two big ones: the risk that an Alu element would hop into a gene and thereby damage the gene, and the related risk that Alu elements would cause other structural damage to genomes. But can these elements be damaging in other ways? If they function as parasites, and if they insist on making RNA in hopes of hopping to another genomic neighborhood, mightn't they pose risks more immediate than mutation? We now know that they do, and we know a little about how humans and other mammals fight back. That's for Part II.

1 comment:

TRGregory said...

Excellent post!