THE brain is the most complicated object known. How it gets that complicated is, however, almost completely unknown. But part of the answer may turn out to be junk—at least that is the conclusion of a study led by Fred Gage of the Salk Institute in La Jolla, California, which has just been published in Nature.

One of the puzzling features of the human genome is that although genes are numerous they actually form less than 5% of the DNA in a cell nucleus. The rest was thus, rather cavalierly, dubbed “junk DNA” by those who discovered it. Gradually, a role for some of this junk has emerged. In particular, parts of it regulate the activity of genes, and thus which proteins are produced and in what quantities. That has implications for what a cell does—or, to put it another way, what type of cell it is. One of the most puzzling sorts of junk, though, is something known as a LINE-1 retrotransposon. This is junk that won't stay in one place.

Retrotransposons are sometimes known as “jumping genes”. They pop from chromosome to chromosome with gay abandon. The assumption has been that they are genetic parasites. They resemble retroviruses, which certainly are parasites (HIV, the cause of AIDS, is a retrovirus). And the effect of a string of irrelevant LINE-1 DNA popping into the middle of a functional gene is indeed traumatic. The gene in question stops working.

The parasite hypothesis is supported by the fact that although bits of DNA that look as if they have once been part of a LINE-1 element make up 20% of the human genome (ie, they are more than four times as abundant as real genes), only 100 retrotransposons are actually able to leap around, and only ten of those leap often. By and large, the parasites have been disabled, suggesting they are such bad news that evolution has eliminated them. Dr Gage and his colleagues, however, suspect that at least some of those that have not been disabled have been allowed to live on for a purpose. Instead of being destroyed, they have been subverted—and what they have been subverted to do is to create complexity in the brain.

Light fantastic

The researchers were led to this idea when they scanned the stem-cell precursors of nerve cells with a device called a gene chip. This detects the activity of genes by measuring the presence of the molecular messengers they send into the cell to do their bidding. To their surprise, the researchers discovered a lot of LINE-1 messengers, suggesting that retrotransposons are active in these precursor cells.

To find out what was going on, Dr Gage and his colleagues built a piece of DNA that included a human LINE-1 retrotransposon; a gene for a molecule called green fluorescent protein (GFP); a genetic switch to turn the whole lot on; and a special sequence of DNA that keeps the switch in the “off” position unless the retrotransposon jumps from one place to another. The result of all this genetic engineering was a system that produces light in cells in which a retrotransposon has jumped. And GFP glows green, as its name suggests, so such cells are easy to spot.

The researchers spliced their creation into the DNA of nerve-cell precursor cells from rats (which they then grew as laboratory cultures). They also spliced it into the DNA of a line of mice, so that it was present in every cell in the mice's bodies.

Nerve-cell precursors can turn into two types of brain cell besides nerve cells. These other two types have supporting, rather than starring roles in the brain, and cannot transmit nerve impulses. The rat-cell work showed that LINE-1 jumping happens only in precursors that turn into nerve cells, and that it seems to be regulated by a protein called Sox2 that is already known to play a crucial role in the formation of nerve cells. The mouse work showed that LINE-1 was not jumping in any other parts of the body (except, oddly, the sex cells—a result that had been seen before). That suggests it is happening in the brain for a purpose.

The mouse work also showed that the retrotransposons were jumping mainly into genes that are active while precursor cells are changing into their destined cell types. The team identified a dozen and a half such genes that were affected by LINE-1, and followed up one of them, PSD-93, in detail. PSD-93 makes a protein found in the places where nerve cells touch each other and pass their signals on. When LINE-1 jumped to a location in the genome near PSD-93 it increased production of the protein. That increase, at least in cell cultures, made it likelier that a developing precursor cell would turn into a nerve cell.

So much is observation. This is where the speculation comes in. Brain formation is an incredibly wasteful process. About half of the nerve cells created in a developing brain have died by the time that brain has formed. Many researchers think that which cells live and which die is decided by a process similar to natural selection. Cells with the right properties in the right places flourish; those without wither. But natural selection requires random variation to generate the various properties.

Retrotransposons could provide that variation, by affecting gene expression at random, depending on where they pitch up. Changing the quantities of proteins such as the one made by PSD-93 would probably change the nature of the affected cell quite radically, and might even be responsible for generating the different types of nerve cell that are known to exist. Certainly, the brain has many more different types of cell in it than any other organ.

A similar idea about generating variation has been proposed in the past, to explain the activity of LINE-1 elements in sex cells. This, the theory goes, would bolster variety in an individual's offspring above and beyond the variation already provided by sexual reproduction. That is an interesting idea. But the thought that the complexity of the mammalian brain—and the existence of human intelligence—depends on variety induced by a tamed genetic parasite is truly audacious. Whether it is true remains to be seen.