National Institutes of Health researchers have identified a gene that makes yeast resistant to a lethal toxin, according to a new study published in the Proceedings of the National Academy of Sciences. To study the evolution of toxin resistance, researchers at the National Human Genome Research Institute (NHGRI), part of NIH, used yeast— the kind commonly used for home baking — as a model organism.
In this current study, NHGRI researchers analyzed yeast infected with a virus that causes the yeast to secrete a lethal toxin called K28. The virus does not negatively affect the infected yeast. Instead, infected yeast are also resistant to the toxin’s effects.
These infected yeast secrete the K28 toxin to wipe out non-infected yeast growing nearby. This provides the infected yeast an evolutionary advantage in the competition for resources. However, some non-infected yeast grow despite the presence of the toxin.
To find out how these non-infected yeast resist the toxin, the researchers exposed different non-infected yeast to the K28 toxin. Those unaffected by the toxin were classified as highly resistant and the affected ones as sensitive. Then, the researchers compared the genomes of resistant versus sensitive yeast to identify which genes cause some yeast to be resistant.
Through this investigation, the researchers determined that the KTD1 gene provides resistance to the K28 toxin.
The researchers then attached a glowing protein to the KTD1 protein to track its position in the yeast cells. They found that the KTD1 protein resides on the surface of cellular compartments called vacuoles. Vacuoles serve many purposes in the cell, including isolating and breaking down harmful substances like toxins.
To inflict its toxic effects, the K28 toxin must move freely around the cell. The researchers hypothesized that the KTD1 protein may be involved in capturing the toxin in the vacuole.
A region of the KTD1 protein pokes into the center of the vacuole, where it could interact with trapped toxins. By analyzing the protein sequence, the researchers found that this region of the KTD1 protein is under strong evolutionary pressures.
