Latino Studies at New York University

Long Qian

PhD Candidate
Kussell Laboratory
Department of Biology
Center for Genomics and Systems Biology
New York University

September 18, 2012

Evolutionary dynamics of restriction site avoidance.

Qian, L and Kussell, E. Phys. Rev. Lett. 2012 Apr 13; 108(15):158105.

Genome evolution is subject to external forces of selection. For example, when the presence of a small sequence motif has negative fitness effects, the genome tends to avoid the motif as it moves in the sequence space via random mutations.  Restriction-Modification (RM) systems are toxin-anti-toxin systems ubiquitously found in bacteria and archaea.  The restriction enzyme recognizes a small sequence motif and cleaves it, destroying DNA; whereas the cognate methylation enzyme methylates the same sites, making them resistant to restriction. In order for the DNA of the host bacterium to be fully protected, all restriction sites in its sequence must be methylated. However, fluctuations in recognition and molecular catalysis could result in unwanted host DNA cleavage. This could potentially explain the apparent underrepresentation of restriction sites in bacterial genomes.  We test this hypothesis by stochastic simulations of the evolutionary process after the introduction of an error-prone RM system, and solve analytically for the equilibrium sequence composition and fitness cost at mutation-selection balance. The results predict avoidance for both the recognition site and the words that have one base mutation from the perfect site - in other words, the adaptation is mutationally robust. Furthermore, avoidance levels show power law scaling with the ratio between the mutation rate and the RM system error rate. At an error rate only a few orders of magnitude higher than the mutation rate, avoidance is already detectable.  Our current work involves analyzing real bacterial genomes for avoidance patterns of the recognition sites of resident RM systems.  Avoidance patterns for all words in the genomes are also analyzed with the goal of understanding the structure of the global pressures a genome experiences throughout its evolutionary history.