Positive Selection of Iris, a Retroviral Envelope–Derived Host Gene in Drosophila melanogaster

Open Access
Publisher Website
Google Scholar
Abstract
Eukaryotic genomes can usurp enzymatic functions encoded by mobile elements for their own use. A particularly interesting kind of acquisition involves the domestication of retroviral envelope genes, which confer infectious membrane-fusion ability to retroviruses. So far, these examples have been limited to vertebrate genomes, including primates where the domesticated envelope is under purifying selection to assist placental function. Here, we show that in Drosophila genomes, a previously unannotated gene (CG4715, renamed Iris) was domesticated from a novel, active Kanga lineage of insect retroviruses at least 25 million years ago, and has since been maintained as a host gene that is expressed in all adult tissues. Iris and the envelope genes from Kanga retroviruses are homologous to those found in insect baculoviruses and gypsy and roo insect retroviruses. Two separate envelope domestications from the Kanga and roo retroviruses have taken place, in fruit fly and mosquito genomes, respectively. Whereas retroviral envelopes are proteolytically cleaved into the ligand-interaction and membrane-fusion domains, Iris appears to lack this cleavage site. In the takahashii/suzukii species groups of Drosophila, we find that Iris has tandemly duplicated to give rise to two genes (Iris-A and Iris-B). Iris-B has significantly diverged from the Iris-A lineage, primarily because of the “invention” of an intron de novo in what was previously exonic sequence. Unlike domesticated retroviral envelope genes in mammals, we find that Iris has been subject to strong positive selection between Drosophila species. The rapid, adaptive evolution of Iris is sufficient to unambiguously distinguish the phylogenies of three closely related sibling species of Drosophila (D. simulans, D. sechellia, and D. mauritiana), a discriminative power previously described only for a putative “speciation gene.” Iris represents the first instance of a retroviral envelope–derived host gene outside vertebrates. It is also the first example of a retroviral envelope gene that has been found to be subject to positive selection following its domestication. The unusual selective pressures acting on Iris suggest that it is an active participant in an ongoing genetic conflict. We propose a model in which Iris has “switched sides,” having been recruited by host genomes to combat baculoviruses and retroviruses, which employ homologous envelope genes to mediate infection. Mobile genetic elements have made homes within eukaryotic (host) genomes for hundreds of millions of years. These include retroviruses that integrate into host genomes as an essential step in their life cycle. While most such integration events are likely to be either deleterious or of little consequence to the host, on rare occasions host genomes can preserve and exploit capabilities of mobile elements for their own function. Especially intriguing are instances where host genomes have chosen to retain the envelope genes of retroviruses; the same envelope genes are responsible for conferring infectious ability to retroviruses. Primates and rodent genomes each have domesticated retroviral envelope genes (called “syncytin” genes) for important roles in placental function. Now, Harmit Malik and colleagues show that a similar, ancient domestication event has taken place within the fruit fly Drosophila melanogaster. They identify a gene, Iris, which was acquired from an envelope gene of insect retroviruses, and has been maintained as a host gene for more than 25 million years. Unexpectedly, the authors find that Iris continues to evolve rapidly whereas previous studies have shown that mammalian syncytin genes do not. They suggest a model in which the Iris gene has “switched sides,” from its original role in causing infections to its current role in preventing them.