  Whether evolution can be predicted is a key question in evolutionary biology.
Here we set out to better understand the repeatability of evolution. We
explored experimentally the effect of mutation supply and the strength of
selective pressure on the repeatability of selection from standing genetic
variation. Different sizes of mutant libraries of an antibiotic resistance
gene, TEM-1 $\beta$-lactamase in Escherichia coli, were subjected to different
antibiotic concentrations. We determined whether populations went extinct or
survived, and sequenced the TEM gene of the surviving populations. The
distribution of mutations per allele in our mutant libraries- generated by
error-prone PCR- followed a Poisson distribution. Extinction patterns could be
explained by a simple stochastic model that assumed the sampling of beneficial
mutations was key for survival. In most surviving populations, alleles
containing at least one known large-effect beneficial mutation were present.
These genotype data also support a model which only invokes sampling effects to
describe the occurrence of alleles containing large-effect driver mutations.
Hence, evolution is largely predictable given cursory knowledge of mutational
fitness effects, the mutation rate and population size. There were no clear
trends in the repeatability of selected mutants when we considered all
mutations present. However, when only known large-effect mutations were
considered, the outcome of selection is less repeatable for large libraries, in
contrast to expectations. Furthermore, we show experimentally that alleles
carrying multiple mutations selected from large libraries confer higher
resistance levels relative to alleles with only a known large-effect mutation,
suggesting that the scarcity of high-resistance alleles carrying multiple
mutations may contribute to the decrease in repeatability at large library
sizes.
