Research on the parasitic portion of DNA genes provides new insights into cellular reproduction systems.
New discoveries from the Stowers Institute for Medical Research reveal key insights into the functioning and survival of a dangerous selfish gene, thought to be a parasitic portion of DNA. Understanding this dynamic is a valuable resource for the community that studies cell reproduction systems.
A new study reveals how a “selfish” gene in yeast uses a venom-antidote strategy that enables its function and likely facilitated its long-term evolutionary success. This strategy is an important addition for scientists studying similar systems, including research groups that are designing synthetic guidance systems for pathogenic pest control. Advances in this area could one day lead to the eradication of pest populations that harm crops or even humans in the case of vector-borne diseases.
Selfish genes are genes that can spread through a population at higher rates than most other genes, without benefiting the organism. Previous research from the Zanders lab revealed that a driver gene in yeast, wtf4 , produces a poisonous protein capable of destroying all offspring. However, for a given parent cell chromosome pair, the effect is achieved when wtf4 is found on only one chromosome. The effect is to simultaneously save only the offspring that inherit the lead allele, by providing a dose of a very similar protein that counteracts the venom, the antidote.
Based on this work, the study developed in the Zanders laboratory, discovered the differences in the timing of generation of the venom and antidote proteins from wtf4 and their unique distribution patterns within the developing spores. The team developed a model they are continuing to study to understand how the venom works to kill the spore (the equivalent of a human egg or sperm in yeast). The results indicate that proteins in the venom clump together, potentially disrupting the proper folding of other proteins necessary for the cell to function. Since the wtf4 gene encodes both venom and antivenom, the latter has a very similar shape and clusters together with the venom.
To understand how selfish genes work during reproduction, the researchers looked at the onset of spore formation and found the venom protein expressed in all developing spores and in the sac surrounding them, while the venom protein antidote was present only in low concentration in the whole bag. Later in development, the antidote became enriched in spores that inherited wtf4 from the yeast parent cell. The researchers found that spores that had inherited the driver gene produced an additional antidote protein within the spore to neutralize the venom and ensure their survival.
The team also found that a particular molecular switch that controls many other genes involved in spore formation also controls the expression of the venom, but not the antivenom, from the wtf4 gene. The switch is essential for yeast reproduction and is inextricably linked to wtf4, helping to explain why this selfish gene successfully evades any host attempts to turn off the switch.
“One of the reasons we think these things have been around for so long is that they used this sneaky strategy of flipping the same essential switch that activates yeast reproduction,” Nidamangala Srinivasa said. “If we could manipulate these DNA parasites to express them in mosquitoes and drive their destruction, it could be a way to control pests,” Nuckolls said.
- S. pombe wtf drivers use dual transcriptional regulation and selective protein exclusion from spores to cause meiotic drive (journals.plos.org