Dr. Eve Syrkin Wurtele (left) and Dr. Ling Li (right). Photo by Christopher Gannon.

Genes that are unique to one species and are not found in the genome of any other organism are called orphan genes. Because they are rare, orphan genes are perceived to lack evolutionary significance and, as a result, their origins and functions are not well-understood.

In 2004, Iowa State University Adjunct Assistant Professor Dr. Ling Li discovered the orphan gene QQS in Arabidopsis, a small flowering plant that is frequently used in scientific research. There was not an obvious indication from the QQS gene sequence as to its function in plants. Studies conducted in collaboration with Iowa State University Professor of Genetics, Development, and Cell Biology Dr. Eve Wurtele identified the function of the Arabidopsis QQS orphan gene – but in soybeans! The research team inserted the QQS gene into soybeans and found QQS increased leaf and seed protein production. This was an unexpected, exciting discovery and Li and Wurtele’s collaboration on QQS resulted in multiple publications and pending patents on expressing the QQS gene in plants.

Li and Wurtele were also curious about the behavior and functionality of the QQS orphan gene in other plants humans eat. If QQS were placed in other plants, would it increase protein production as it did in soybeans?

As described in an article published in the Proceedings of the National Academy of Sciences (PNAS), Li and Wurtele showed that the introduction of QQS into staple crops such as rice and corn also resulted in increased protein content without affecting crop yields. On a larger scale, this work could help meet the nutritional needs of people living in areas of the world where dietary protein is often insufficient. Protein-heavy plants present a more sustainable source of protein than animals.

With help from Professor of Genetics, Development, and Cell Biology Dr. Yanhai Yin, the investigators also discovered that QQS binds to a protein common to plants and animals, known as NF-YC4; an increase in NF-YC4 production also increases leaf and seed protein.  The production of this protein can be altered in crop species using an approach that doesn’t require safety testing. As a result, researchers think NF-YC4 may be the key to creating high-protein crops faster and cheaper, saving years of research and hundreds of millions of dollars. Dr. Li noted, “By producing more of the NF-YC4 gene in staple crops, researchers can increase the protein value of plants without using transgenes (exogenous genes), which could save time and money in the regulatory process.”

Work such as this, can open the door to many more discoveries, leading scientists to better appreciate the potential and value of studying orphan genes. “This is one orphan gene that we’ve shown has big potential,” Wurtele said. “And we believe there will be many more discoveries related to other orphan genes in the future.”

When asked about the broader impacts of her research, Dr. Li responded:

“Our goal is to use our finding to increase the protein content of staple crops in regions where humans have high rates of protein deficiency. Five graduate students and 17 undergraduate students have participated in computational and experimental research as part of our research. Four postdocs have gone directly on to promising academic or industrial careers.

We are also dedicated to disseminating results that that have been achieved with the help of NSF-MCB support. In the past four years, we have presented over 35 invited seminars at universities, institutes, and conferences in eight countries sharing our research results. We have held fourteen hands-on workshops on the MetNet bioinformatics platform tools that helped us identify the role of QQS, NF-YC-4, and other genes.  We have also created an interactive computer game called Meta!Blast, which is designed to teach cross-cutting science concepts, and is being used in undergraduate classrooms and as an exhibit in science museums.”

This work is funded by the Division of Molecular and Cellular Biosciences, Award #MCB-0951170 and by the Division of Integrative Organismal Systems, Award #IOS-1257631 in the Directorate for Biological Sciences.