RESEARCH

The Paradox

DNA packaging into chromatin mediates chromosome segregation, telomere protection, genome integrity, and other essential, conserved cellular processes. However, many chromatin proteins are strikingly unconserved—domains and residues evolve rapidly between even closely related species. This paradox of conserved, chromatin-dependent functions supported by fast-evolving chromatin proteins suggests that maintaining essential cellular processes requires recurrent innovation. The biological significance of this innovation is virtually unexplored. With few exceptions, we understand neither the evolutionary forces that shape contemporary chromatin proteins nor the chromatin-dependent functions modified by recent adaptation. Nevertheless, aberrant chromatin packaging is the hallmark of many blood and tumor cancers, chromosomal birth defects, and aging.

The Resolution

The paradoxical observation of conserved functions supported by fast-evolving chromatin indicates that some chromatin-dependent processes require recurrent innovation. We hypothesize that evolutionary battles between a host genome and its selfish genetic elements drive these chromatin innovations. Unlike the rest of our genome, selfish elements increase in frequency over evolutionary time at the expense of host fitness. Compromised fitness puts evolutionary pressure back on the host to suppress selfish activity, perpetuating a “molecular arms race” (see above). Host protein innovations may appear as the rapid accumulation of amino acid-changing mutations or even the birth of entirely new proteins (see below).

 

Our Approach

Host genomes evolve rapidly under positive selection to suppress the collateral damage of selfish element proliferation. This efficient suppression renders selfish elements cryptic in contemporary genomes. To study the molecular mechanisms of cheating and suppression, we using CRISPR/Cas9 gene editing to effectively reverse host suppressor protein evolution. This “evolutionary mismatch” between a resurrected host protein and contemporary selfish elements awakens cheating in real time. Using a combination of cell biology, chromatin biochemistry, and next generation RNA and DNA sequencing, we study the mechanisms of cheating and mechanisms of host suppression. Importantly, these experiments reveal how past evolutionary battles shape ostensibly conserved chromatin-dependent processes like chromosome transmission, telomere protection, and genome integrity.

 

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