Speaker
Arjan de Visser
Description
Although evolution is inherently stochastic due to chance events, such
as mutations, it is not fully random due to deterministic consequences
of natural selection and constraints imposed by the fitness landscape. A
better understanding of the causes and constraints of evolution will
help to control the evolution of unwanted phenotypes, such as
antibiotic-resistant pathogens. I will present results from evolution
experiments with the notorious antibiotic resistance enzyme, TEM-1
beta lactamase, in the presence of a novel antibiotic. We use both in
vitro (only TEM) and in vivo (TEM + host) evolution experiments to
address the effect of population size on the tempo and mode of
adaptation. The results from in vitro experiments show greater
adaptive heterogeneity and surprisingly higher resistance in small than
in large populations, reflecting the rugged fitness landscape of the
enzyme. In the in vivo experiments, we find no adaptive benefit for
small populations – suggesting a more smooth adaptive landscape, but
differential effects from population size on the repeatability of different
mutation classes: large populations show more parallel SNPs, while
small populations show more parallel large genomic deletions and
duplications. We are testing the hypothesis that this divergent pattern
of parallel evolution derives from clonal interference benefitting lower-
rate, but larger-benefit SNPs in populations large enough for both
classes of mutations to occur.
Primary author
Arjan de Visser
