Abstract: Series 116, Lecture 5

The Harvey Lectures Series 116 (2022—2023)

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Lecture #5: Thursday, March 16, 2023 — Watch Video of Lecture

Red Queen rules: genetic conflicts shape biology

Harmit Malik, PhD

Harmit Malik, PhD

Professor and Associate Director Basic Sciences Division
Investigator, Howard Hughes Medical Institute

Howard Hughes Medical Institute
Fred Hutchinson Cancer Research Center

Seattle, Washington

Dr Malik's Website

Selfishness is pervasive and manifests at all scales of biology, from societies, to individuals, to genetic elements within a genome. The relentless struggle to seek evolutionary advantages drives perpetual cycles of adaptation and counter- adaptation, commonly referred to as Red Queen interactions. In this talk, I will share insights gleaned from molecular and genetic studies of such genetic conflicts, both extrinsic (between genomes) and intrinsic (within genomes or cells). An example of extrinsic conflict is the ancient and ongoing challenge posed by viral infections on mammalian genomes, which lead to signatures of genetic innovation. These genetic imprints can be identified via evolutionary analyses to reveal fundamental details about when (how old), where (which protein domains), and how (what are the functional consequences of adaptive changes) host-virus arms races alter the proteins involved. Just as extreme amino acid conservation can serve to identify key immutable residues in enzymes, positively selected residues point to molecular recognition interfaces between host and viral proteins that have adapted and counter-adapted in a long series of classical Red Queen conflicts. Similarly, we are interested in intrinsic genetic conflicts between chromosomes that vie for evolutionary supremacy during transmission to the next generation. My lab has focused on such battles during meiosis that shape the evolution of centromeric DNA and proteins (which mediate proper chromosome segregation), that may ultimately underlie the origin of biological species.