Quasi-species evolution maximizes genotypic reproductive value (not fitness or flatness)

Growing efforts to measure fitness landscapes in molecular and microbial systems are motivated by a longstanding goal to predict future evolutionary trajectories. Sometimes under-appreciated, however, is that the fitness landscape and its topography do not by themselves determine the direction of evolution: under sufficiently high mutation rates, populations can climb the closest fitness peak (survival of the fittest), settle in lower regions with higher mutational robustness (survival of the flattest), or even fail to adapt altogether (error catastrophes). I show that another measure of reproductive success, Fisher's reproductive value, resolves the trade-off between fitness and robustness in the quasi-species regime of evolution: to forecast the motion of a population in genotype space, one should look for peaks in the (mutation-rate dependent) landscape of genotypic reproductive values-whether or not these peaks correspond to local fitness maxima or flat fitness plateaus. This new landscape picture turns quasi-species dynamics into an instance of non-equilibrium dynamics, in the physical sense of Markovian processes, potential landscapes, entropy production, etc.