Fall Seminar Series - Dr. Eric Lai, Weill Cornell Medicine

Event Title:

• Host: Dr. Howard Lipshitz, Departmental Seminar Series
• Date: Monday, October 23rd, 2023
• Time: 3:00 PM
• Location: Room 254 (MC) Mechanical Engineering Building

Speaker:

• Speaker: Eric Lai, PhD
• Affiliations:
  • Member, Memorial Sloan Kettering Cancer Center, New York
  • Professor, Weill Cornell Graduate School of Medical Sciences, New York

Seminar Topic:

• Title: The Red Queen and the Lost Boys: Intragenomic Conflict and Endogenous RNAi in the Male Germline
• Abstract: Selfish meiotic drive systems (SMDs) can distort progeny sex-ratio (SR) and/or induce sterility. Although widespread in nature, the molecular mechanisms of SMDs, and how they are silenced to restore Mendelian segregation, remain largely mysterious. Importantly, their rapid evolution means that classic model organisms may not be suited to reveal their fundamental features, breadth, and impact. Using the nonmodel fruit fly D. simulans (Dsim), we uncovered critical roles for hpRNA-class RNAi substrates to suppress incipient sex chromosome conflicts. These arose in the simulans-clade ancestor and are not found in their close relative D. melanogaster. Strikingly, knockouts of Dsim hpRNA-siRNA loci (Nmy and Tmy) exhibit profound defects in the male germline, leading to the loss of male progeny or outright sterility. These phenotypes are due to de-repression of recently-evolved members of the "Dox" family, which derived in part from protamine. Protamines mediate condensation of sperm chromatin, raising the possibility that these programs of meiotic drive interfere with packaging the paternal genome. Further analysis of core RNAi mutants in Dsim reveals additional de novo X-linked genes that are suppressed by recently-evolved hpRNAs. Thus, there is broad, unanticipated complexity in rapidly-evolving sex chromosome conflicts. Altogether, these data reveal one of the most overt biological usages of RNAi, and suggest a role for RNA silencing in speciation.