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Study of Parasitic Wasp Venom Reveals Novel & Possibly Widespread Mechanism for Genes to Evolve New Functions; Parasitoid Venoms May Offer “Immense Untapped Cornucopia for Drug Discovery”

Amid the incredible diversity of living things on our planet, there is a common theme. Organisms need to acquire new genes, or change the functions of existing genes, in order to adapt and survive. How does that happen? A common view is that genes are duplicated, with one of the copies picking up a new function while the other copy continues to function as before. However, by studying tiny parasitic Jewel Wasps and their rapidly changing venom repertoires, the Werren Lab at the University of Rochester in New York has uncovered a different process that may be widespread in other species as well. The process involves co-opting single-copy genes to take on new functions. In some cases, these genes appear to continue their previous function as well, in other parts of the wasp's anatomy besides the venom gland. The findings are published in Current Biology. The article is titled “The Evolution of Venom by Co-option of Single-Copy Genes.” "It is almost as if they are now moonlighting," says John (Jack) Werren, Professor of Biology. "They've got a day job, and then take on a night job as well. Over time, if the night job works out, they may give up the day job and evolve as a venom specialist. However, in other cases, we have found that they stop moonlighting as venom genes, but appear to retain their day job." How is a gene co-opted? And what determines which job (or combination of jobs) it performs? In the case of Jewel Wasps, the process called gene regulation is key. As the researchers explain, the rapid turnover in venom genes is accomplished mostly by changes in regulatory regions adjacent to the genes. These regulatory regions control how the genes are expressed--that is, whether the genes are turned "on" or "off" in different tissues. When a gene is turned on, it provides instructions for manufacturing proteins. When it's turned off, it provides no such instructions.

"Co-option of single-copy genes can be a more rapid mechanism for adapting to a new environment because it does not require the gene to be duplicated first," notes Ellen Martinson, PhD, a co-lead author and postdoctoral research associate in the Werren Lab.

"In essence, these wasps are recycling their genes for new functions," says co-lead Dr. Mrinalini, a former postdoc in the Werren Lab who has since joined the National University of Singapore, where she studies snake venoms.

The group--which also includes two other researchers at the University of Rochester, Yogeshwar Kelkar and Ching-Ho Chang--studied four closely related species of Jewel Wasps. The wasps lay their eggs on the pupae of other insects, after first injecting the pupae with venoms that manipulate the metabolism of the host in ways that make the environment more conducive to their developing young.

Using transcriptome and proteome sequencing, the researchers found that more than half of the venom components in the parasitic wasps resulted from single-copy genes that had been co-opted without being duplicated. The composition of the venoms can change quickly, allowing the wasps to adapt to different hosts. For example, even closely related species can differ by up to 40 percent of their venom repertoire.

The group proposes that co-option of single-copy genes for new function is not just restricted to parasitoid venoms. Co-option may be common in nature, particularly when organisms are evolving rapidly to changing environments.

With regards to parasitoid venoms, there may be an added benefit, says Dr. Werren. "The great diversity of parasitoid venoms and abundance of these species (estimates run as high as 600,000 parasitoid species on earth), combined with the fact that parasitoid venoms have evolved to manipulate metabolic processes, suggests that they are potentially an immense untapped cornucopia for drug discovery."

[Press release] [Current Biology abstract]