Intra-genomic conflict and the preservation of genome integrity

Department of Biology Seminar Series
Dr. Mia Levine, Upenn
- | Leidy 10 Auditorium

Selfish DNA elements infest eukaryotic genomes. These “genome parasites” act akin to viruses, hijacking our cell’s machinery to increase their copy number in the host genome. Such selfish element proliferation can compromise host fitness, putting evolutionary pressure on the host genome to suppress selfish elements. Suppressed selfish elements then counter-adapt, escalating a “molecular arms race.” My lab seeks to define the identity, molecular mechanisms, and biological consequences of the ongoing conflict between genome hijackers and genome guardians. Defining and dissecting intra-genomic conflicts, however, has proved challenging. Efficient suppression by genome guardians allows selfish elements – and the biology hijacked by selfish elements – to hide in plain sight. To overcome this challenge, my lab first exploits evolutionary genetics and genomics to home in on conflict. Specifically, we scan genomes for recent genetic innovation, e.g., rapid evolution shaped by positive selection. We next transgenically replace positively selected host guardian genes with naïve versions derived from closely related species. The perturbed genotype represents an “evolutionary mismatch” between the contemporary host guardian gene from one species and the contemporary selfish elements of another. These carefully engineered animals reawaken selfish elements and/or resurrect the detrimental biological consequences of ancient selfish element proliferation. By disrupting the temporary truce between two antagonistic genetic parties, we can study the otherwise invisible biology sculpted by recent adaptive evolution. My seminar will describe two such investigations of potential intra-genomic conflict: conflict between repetitive telomeric mobile elements and a telomere-packaging protein and conflict between a DNA satellite repeat and a DNA satellite-packaging protein. These studies together reveal that recurrent innovation of DNA packaging is required to preserve genome integrity in the face of ever-evolving repetitive DNA.


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