RNA-only genes: The origin of species? THE old saying that where there's muck, there's brass has never proved more true than in genetics. Once, and not so long ago, received wisdom was that most of the human genome - perhaps as much as 99% of it - was "junk." If this junk had a role, it was just to space out the remaining 1%, the genes in which instructions about how to make proteins are encoded, in a useful way in the cell nucleus. That, it now seems, was about as far from the truth as it is possible to be. The decade or so since the completion of the Human Genome Project has shown that lots of the junk must indeed have a function. The culmination of that demonstration was the publication, in September, of the results of the ENCODE project. This suggested that almost two-thirds of human DNA, rather than just 1% of it, is being copied into molecules of RNA, the chemical that carries protein-making instructions to the sub-cellular factories which turn those proteins out, and that as a consequence, rather than there being just 23,000 genes (namely, the bits of DNA that encode proteins), there may be millions of them. The task now is to work out what all these extra genes are up to. And a study just published in Genome Biology, by David Kelley and John Rinn of Harvard University, helps do that for one new genetic class, a type known as lincRNAs. In doing so, moreover, Dr Kelley and Dr Rinn show just how complicated the modern science of genetics has become, and hint also at how animal species split from one another. Lincs in the chain Molecules of lincRNA are similar to the messenger-RNA molecules which carry protein blueprints. They do not, however, encode proteins. More than 9,000 sorts are known, and most of those whose job has been tracked down are involved in the regulation of other genes, for example by attaching themselves to the DNA switches that control those genes. LincRNA is rather odd, though. It often contains members of a second class of weird genetic object. These are called transposable elements (or, colloquially, "jumping genes," because their DNA can hop from one place to another within the genome). Transposable elements come in several varieties, but one group of particular interest are known as endogenous retroviruses. These are the descendants of ancient infections that have managed to hide away in the genome and get themselves passed from generation to generation along with the rest of the genes. Dr Kelley and Dr Rinn realised that the movement within the genome of transposable elements is a sort of mutation, and wondered if it has evolutionary consequences. Their conclusion is that it does, for when they looked at the relation between such elements and lincRNA genes, they found some intriguing patterns. In the first place, lincRNAs are much more likely to contain transposable elements than protein-coding genes are. More than 83% do so, in contrast to only 6% of protein-coding genes. Second, those transposable elements are particularly likely to be endogenous retroviruses, rather than any of the other sorts of element. Third, the interlopers are usually found in the bit of the gene where the process of copying RNA from the DNA template begins, suggesting they are involved in switching genes on or off. And fourth, lincRNAs containing one particular type of endogenous retrovirus are especially active in pluripotent stem cells, the embryonic cells that are the precursors of all other cell types. That indicates these lincRNAs have a role in the early development of the embryo. Previous work suggests lincRNAs are also involved in creating the differences between various sorts of tissue, since many lincRNA genes are active in only one or a few cell types. Given that their principal job is regulating the activities of other genes, this makes sense. Even more intriguingly, studies of lincRNA genes from species as diverse as people, fruit flies and nematode worms, have found they differ far more from one species to another than do protein-coding genes. They are, in other words, more species specific. And that suggests they may be more important than protein-coding genes in determining the differences between those species. What seems to be happening is that endogenous retroviruses are jumping around in an arbitrary way within the genome. Mostly, that will - in evolutionary terms - be either harmless or bad. Occasionally, though, a retrovirus lands in a place where it can change the regulation of a lincRNA gene in a way beneficial to the organism. Such variations are then spread by natural selection in the way that any beneficial mutation would be. But because they affect developmental pathways and tissue types, and thus a creature's form, rather than just its biochemistry, that could encourage the formation of a new species. This is a long chain of speculation, but it looks a fruitful one. For it is still the case that, more than a century and a half after Charles Darwin published "On the Origin of Species," biologists do not fully understand how species actually do originate. Work like this suggests one reason for this ignorance may be that they have been looking in the wrong place. For decades, they have concentrated their attention on the glittering, brassy protein-coding genes while ignoring the muck in which the answer really lies.