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On the Origin of CRISPR
- Yoon, Peter
- Advisor(s): Doudna, Jennifer A
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Abstract
A fundamental question in biology is how evolution builds molecular machines. Understanding these design strategies can guide molecular tool engineering and reveal hidden natural systems. The RNA-guided immune system CRISPR-Cas is an ideal testbed due to its diversity and complexity. By developing a structure-based search that couples rapid clustering with sensitive alignments, I mined databases of predicted structures for divergent, otherwise undetectable homologs of CRISPR proteins. This thesis traces CRISPR's origins, explains why its proteins grow complex, and shows how related systems are repurposed for new functions, revealing evolution's playbook for building molecular machines.