Long terminal repeat retrotransposons jump between species.

R are an evolutionarily ancient class of mobile genetic elements that transpose replicatively within their host genomes via RNA intermediates. There are three major retrotransposon groups, the Ty1-copia group and the gypsy group long terminal repeat (LTR) retrotransposons and the non-LTR retrotransposons or LINE elements (ref. 1; Fig. 1). All three groups are widespread in the eukaryotes, although none of the LTR retrotransposon groups have been detected in mammals or birds as yet. All LTR retrotransposons share striking sequence similarities with the retroviruses of vertebrates, and at least one LTR retrotransposon of Drosophila is in fact an infectious retrovirus (2). It is universally believed that modern day retroviruses, LTR retrotransposons, and non-LTR retrotransposons share a common ancestor, though there is some dispute about which came first (1, 3, 4). Retrotransposons may look a lot like retroviruses, but they are not by themselves infectious. The basic difference between a retrotransposon and a retrovirus is the retrotransposon’s lack of an envelope glycoprotein gene. This crucial difference prohibits the formation of an extracellular infectious virus particle, leaving the retrotransposon virus-like particle marooned inside its host cell (5). LTR retrotransposons cannot normally transfer themselves between adjacent cells; they certainly cannot move readily from one animal to another, and even more certainly, they cannot transfer horizontally from one species into another. In that case, why is there a paper in this issue of PNAS that proves beyond all reasonable doubt that an LTR retrotransposon called copia has been transferred from one species of Drosophila, Drosophila willistoni, into another, Drosophila melanogaster, within the last 200 years (6)? We will address that question a little later in the article, but first, let us quickly review the evidence that supports the author’s conclusions. The copia element of D. melanogaster was among the first LTR retrotransposons to be discovered (7). It is ubiquitous in D. melanogaster, and it has a broad distribution in other Drosophila species (8). D. willistoni is a copia-containing species, but copia is absent from many willistoni strains (6). Jordan et al. (6) have cloned and sequenced a fragment of the D. willistoni copia. This 1-kilobase fragment is identical to the most famous and well used copia clone, the white-apricot copia that was isolated from a spontaneous insertion of copia into the white locus of D. melanogaster (9, 10). Total sequence conservation of a retrotransposon across the 50-million-year gap that separates these two species is simply unbelievable; thus, either the transposon has jumped between the two species much more recently than their common ancestor, or there was some kind of contamination artifact in the experiment. Indeed, this observation set an alarm bell ringing for me, because this particular copia is also a clone that most fly labs have in their fridges and freezers. However, the whiteapricot copia is also very successful at transposing in real f lies, and it is reasonable to suppose that it was the one that was lucky enough to jump across into D. willistoni. The authors were no doubt as worried as I and have carried out a formidable series of controls to prove beyond any reasonable doubt that the D. willistoni genome does in fact contain integrated copia that is virtually identical to the whiteapricot copia. The usual negative controls are all there to show that the tubes and solutions are clean. Southern analysis shows that there is a significant amount of copia present in the D. willistoni genome— not the tiny amount that would suggest contamination—and two further rigorous PCR controls prove that the D. willistoni DNA samples contain absolutely no contaminating copies of two D. melanogaster genes. Lastly, a D. willistoni genomic library has yielded a copia clone that is identical to the white-apricot copia. Thus, copia has been transferred between two quite distantly related species of Drosophila. These two species have shared a host range for only the past 200 years. D. willistoni is a New World species and D. melanogaster was an African species until it began following humans—or, to be more precise, their rotting fruit— around the world. Moreover, in that time, another transposon has been transferred between these two species. The P element of D. melanogaster, which gained fame as a vector for germ-line transformation of that species, has been transferred from the D. willistoni subgroup, probably in this century (11). The two transfers of mobile elements have thus been reciprocal. Moreover, these two transposons are mechanistically very distinct from each other; the P element is a classical DNA transposable element that uses a DNA transposition intermediate. Any mechanism proposed to explain both transfers must take these observations into account. What possible mechanisms are there? The evolutionary gap between these two species is almost certainly too large for even an abortive mating (M. Ashburner, personal communication); thus, the answer must be that a vector was responsible for the transfer. The most plausible candidate is a parasite with a broad species range, such as the mite Proctolaelaps regalis, which was proposed as a vector for the transfer of the P element (12). This hypothesis is attractive, because this mite feeds on Drosophila eggs by punching holes, sucking out the contents, and then moving on. P. regalis is a messy eater that does not kill every egg that it attacks, and it is reasonable to assume that it could transfer small amounts of the contents of one egg into another. Such a procedure could easily induce the transfer of the P element, and it is very plausible that transfer of the copia virus-like particle would also result in horizontal transfer. The egg interior is the cytoplasm of a very large single cell, and the cytoplasm is a known intracellular location of the copia virus-like particle (13), which contains all of the necessary machinery for introducing a new copy of the retrotransposon into the genome. Unfortunately, this hypothesis is very difficult to substantiate in the laboratory. Nonetheless, it may well be that many of the possible classes of vector have at one time or another managed to ferry transposons from one species to another. Such possible vectors include other kinds of ani-