WOX9: A gene that's a jack of all trades

Over evolutionary time scales, a single gene may acquire different roles in diverging species. However, revealing the multiple hidden roles of a gene was not possible before genome editing came along. Cold Spring Harbor Laboratory scientists Zach Lippman and Anat Hendelman collaborated with Idan Efroni of Hebrew University in Israel to reveal hidden gene functions. The results are published in the journal Cell.

In U.S. National Science Foundation-funded research, the scientists dissected the activity of a developmental gene, WOX9, in different plants at different moments in development. Using genome editing, they found that without changing the protein produced by the gene, they could change a plant's traits by changing the gene's regulation.

Genes are the DNA that code for proteins, but other nearby stretches of DNA regulate the activity of genes, instructing them where, when, and to what degree they should be active. With the genome-editing tool CRISPR, scientists can introduce precise mutations into DNA, including these regulatory regions.

Though scientists would like to use CRISPR to fine-tune plant traits, the technique sometimes yields surprising results: Some genes turn out to have functions that were previously unknown.

WOX9 is one of several genes that help plants and animals set borders in developing structures. While the gene plays a role in early development in Arabidopsis, a weedy relative of broccoli, it influences later development -- reproduction and flowering -- in tomatoes.

Lippman and Hendelman used CRISPR to create a series of mutations in the regulatory DNA surrounding WOX9 to reveal additional functions in tomato, groundcherry and Arabidopsis plants.

With the right regulatory sequence, the gene could induce more flowers to form in all three species. WOX9 is thus a candidate to increase yields in these and other crop plants by changing its regulation. The discovery suggests that other genes may also have hidden multiple roles.

"Only a few percent of plant and animal genomes encode genes, with the vast majority of the genome made up of regulatory sequences controlling when, where, and at what level genes are expressed into proteins," says Gerald Schoenknecht, a program director in NSF's Division of Integrative Organismal Systems. "This research begins to give us insights into this phenomenal regulatory network."