  Background: Recent experimental and theoretical studies have shown that small
asexual populations evolving on complex fitness landscapes may achieve a higher
fitness than large ones due to the increased heterogeneity of adaptive
trajectories. Here we introduce a class of haploid three-locus fitness
landscapes that allows to investigate this scenario in a precise and
quantitative way.
  Results: Our main result derived analytically shows how the probability of
choosing the path of largest initial fitness increase grows with the population
size. This makes large populations more likely to get trapped at local fitness
peaks and implies an advantage of small populations at intermediate time
scales. The range of population sizes where this effect is operative coincides
with the onset of clonal interference. Additional studies using ensembles of
random fitness landscapes show that the results achieved for a particular
choice of three-locus landscape parameters are robust and also persist as the
number of loci increases.
  Conclusions: Our study indicates that an advantage for small populations is
likely whenever the fitness landscape contains local maxima. The advantage
appears at intermediate time scales, which are long enough for trapping at
local fitness maxima to have occurred but too short for peak escape by the
creation of multiple mutants.
