The wtf4 meiotic driver utilizes controlled protein aggregation to generate selective cell death

Area of Science:

• Genetics
• Molecular Biology
• Cell Biology

Background:

• Meiotic drivers are genetic elements that bias their own inheritance.
• The molecular mechanisms of most meiotic drivers remain largely unknown.
• The wtf4 gene in Schizosaccharomyces pombe is a known meiotic driver utilizing a poison-antidote mechanism.

Purpose of the Study:

• To investigate the molecular mechanism of the wtf4 meiotic driver.
• To determine if Wtf4 proteins can function in a distantly related species.
• To elucidate how the Wtf4 poison is neutralized.

Main Methods:

• Expression of Wtf4 poison and antidote proteins in Saccharomyces cerevisiae.
• Analysis of protein aggregation and trafficking using microscopy.
• Assessment of cell viability upon expression of Wtf4 proteins and mutants.

Main Results:

• Wtf4 poison protein forms toxic aggregates.
• Wtf4 antidote protein co-assembles with Wtf4 poison and promotes its trafficking to vacuoles.
• Disruption of co-assembly or trafficking leads to cell death, indicating neutralization is dependent on these processes.

Conclusions:

• The Wtf4 meiotic driver system can function in heterologous species.
• Neutralization of Wtf4 poison requires both antidote co-assembly and aggregate trafficking to vacuoles.
• Meiotic drivers can exploit cellular protein aggregate management pathways for spore destruction.