Functional constraints of wtf killer meiotic drivers

Area of Science:

• Genetics
• Molecular Biology
• Evolutionary Biology

Background:

• Killer meiotic drivers are selfish genetic elements that reduce the transmission of non-driver alleles.
• These drivers often utilize toxic proteins to eliminate gametes lacking the driver.
• Understanding driver mechanisms offers insights into infertility and fundamental cellular processes.

Purpose of the Study:

• To elucidate the molecular mechanisms of the wtf family of killer meiotic drivers in fission yeast.
• To investigate the role of protein self-assembly in Wtfpoison toxicity and neutralization.
• To explore the evolutionary constraints on killer meiotic driver genes.

Main Methods:

• Analysis of wtf gene family evolution and protein conservation.
• Investigating Wtfpoison self-assembly and its correlation with toxicity.
• Engineering wtf alleles to study driver-antidote interactions and self-destructive potential.

Main Results:

• Self-assembly of Wtfpoison proteins is conserved and linked to toxicity, despite low amino acid sequence similarity.
• Wtfpoison toxicity is modulated by the extent of protein assembly.
• Specific co-assembly of Wtfpoison and Wtfantidote proteins is crucial for effective neutralization.
• Engineered self-destructive wtf alleles demonstrate functional constraints on driver evolution.

Conclusions:

• Wtfpoison self-assembly is a conserved mechanism driving toxicity in killer meiotic drivers.
• The size of Wtfpoison assemblies influences toxicity, and co-assembly with Wtfantidotes is key for neutralization.
• Self-destructive alleles highlight evolutionary limits and suggest a role in fission yeast infertility.
• Analogous self-killing drivers may contribute to infertility across diverse eukaryotic lineages.