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Background: Recent experimental and theoretical studies have shown that smallasexual populations evolving on complex fitness landscapes may achieve a higherfitness than large ones due to the increased heterogeneity of adaptivetrajectories. Here we introduce a class of haploid three-locus fitnesslandscapes that allows to investigate this scenario in a precise andquantitative way.  Results: Our main result derived analytically shows how the probability ofchoosing the path of largest initial fitness increase grows with the populationsize. This makes large populations more likely to get trapped at local fitnesspeaks and implies an advantage of small populations at intermediate timescales. The range of population sizes where this effect is operative coincideswith the onset of clonal interference. Additional studies using ensembles ofrandom fitness landscapes show that the results achieved for a particularchoice of three-locus landscape parameters are robust and also persist as thenumber of loci increases.  Conclusions: Our study indicates that an advantage for small populations islikely whenever the fitness landscape contains local maxima. The advantageappears at intermediate time scales, which are long enough for trapping atlocal fitness maxima to have occurred but too short for peak escape by thecreation of multiple mutants.

Evolutionary advantage of small populations on complex fitness landscapes