Cara Brand

​Eukaryotic genomes are riddled with DNA repeats such as transposable elements and non-coding, tandemly repeating DNA satellites. For decades, the absence of obvious functional elements, combined with impediments to genetic manipulation and sequencing, led to benign neglect. However, new long-read sequencing technologies have enabled Telomere-to-Telomere assemblies that span the satellite-rich regions of eukaryotic genomes, including our own. These studies have revealed that repetitive DNA comprises an astounding >180 million base pairs of the human genome, underscoring its potential to profoundly shape human health, reproduction, and genome evolution.

Repetitive DNA evolves rapidly—between even closely related species, repetitive genomic regions are highly diverged and often completely unalignable. Paradoxically, these unconserved genomic regions support deeply conserved cellular functions vital for organismal survival and reproduction. A widely cited model of intra-genomic coevolution proposes a resolution to this paradoxical observation: to maintain conserved cellular functions, essential proteins that interact with DNA repeats evolve adaptively to mitigate deleterious changes in DNA repeat copy number, sequence, and organization. Repeated bouts of repetitive DNA turnover coupled with protein adaptation can drive rapid molecular adaptation and contribute to the formation of reproductive barriers between species.

This framework was proposed over two decades ago, yet there are exceedingly few cases in which both the DNA repeats and the proteins engaged in intra-genomic coevolution have been identified and functionally characterized. Moreover, in a contemporary genome, the once-threatening satellites are rendered harmless by their coevolved satellite-interacting proteins, effectively hiding in plain sight. These gaps hinder our ability to understand the cellular functions and molecular machinery shaped by intra-genomic coevolution, as well as the potential of these arms races to trigger genetic incompatibilities that drive reproductive isolation. My research aims to uncover the functional and evolutionary consequences of intra-genomic coevolution.