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.