The eco-evolutionary costs and benefits of CRISPR-Cas systems, and their effect on genome diversity within populations
CRISPR-Cas systems and population-wide genomic diversity
CRISPR-Cas systems are microbial defense systems that provide prokaryotes with acquired and heritable DNA-based immunity against selfish genetic elements, primarily viruses. Since CRISPR-Cas systems can impede lateral gene transfer, and facilitate speciation, it is often assumed that they reduce genetic diversity. However, paradoxically these systems often allow the maintenance of high levels of genomic diversity within populations. We are combining comparative genomics, metagenomics, and experimental evolution to characterize the roles that CRISPR-Cas systems play in genome evolution.
CRISPR-Cas systems and DNA repair
CRISPR-Cas systems include CRISPR-associated (Cas), genes that can have helicase and nuclease functions and can therefore interact with the DNA repair machinery of the cell, as has been shown in bacteria. We have been investigating how Cas genes affect DNA repair in archaea and have recently shown that knocking out some Cas genes or parts of them, increased cell survival after DNA damage, implying that CRISPR-Cas systems can be costly for the cell to maintain, under such conditions. We are now exploring the genetic and molecular basis for the interaction between the Cas genes in question and DNA repair.
CRISPR-Cas systems and DNA recombination
Our studies on DNA integration via recombination in various knock-out strains, and of cases where we engineered one strain to target another's DNA during archaeal cell-cell mating show that CRISPR-Cas systems affect recombination location and frequency.
The best defense can be a great offense
In many organisms, including archaea, CRISPR-Cas systems are encoded by selfish genetic elements, such as plasmids or viruses that are using those systems to target competitors. This results in unexpected genetic conflicts and consequences for the genomes of strains and the pan-genomes of populations.