Edinburgh Research Explorer Beyond the Hypercube

Evolutionary pathways describe trajectories of biological evolution in the space of different variants of organisms (genotypes). The probability of existence and the number of evolutionary pathways that lead from a given genotype to a better-adapted genotype are important measures of accessibility of local fitness optima and the reproducibility of evolution. Both quantities have been studied in simple mathematical models where genotypes are represented as binary sequences of two types of basic units, and the network of permitted mutations between the genotypes is a hypercube graph. However, it is unclear how these results translate to the biologically relevant case in which genotypes are represented by sequences of more than two units, for example four nucleotides (DNA) or 20 amino acids (proteins), and the mutational graph is not the hypercube. Here we investigate accessibility of the best-adapted genotype in the general case of K > 2 units. Using computer generated and experimental fitness landscapes we show that accessibility of the global fitness maximum increases with K and can be much higher than for binary sequences. The increase in accessibility comes from the increase in the number of indirect trajectories exploited by evolution for higher K . As one of the consequences, the fraction of genotypes that are accessible increases by three orders of magnitude when the number of units K increases from 2 to 16 for landscapes of size N * 10 6 genotypes. This suggests that evolution can follow many different trajectories on such landscapes and the reconstruction of valleys (unfit ones). To address this question we investigate how likely it is for biological evolution to find a way “uphill” from a lower-fitness organism to the best adapted organism. We discover that the accessibility of the fittest organism depends on the number of types of basic “units” used to encode genotypes. These units can be, for example, the four DNA nucleotides A,T,C,G, or the * 20 amino acids used for synthesizing proteins, and the choice of the most appropriate unit is dictated by how the genotypes and the fitnesses are related—a relationship that researchers have begun to unveil only recently. We find that increasing the number of units strongly increases the probability that there will be at least one uphill path to the best-adapted genotype, and the number of evolutionary pathways leading to it. Our findings suggest that biological evolution can follow many more pathways than previously thought.