Ard Louis

Abstract:

Unravelling the structure of genotype–phenotype (GP) maps is an important problem in biology. Recently, arguments inspired by algorithmic information theory (AIT) and Kolmogorov complexity have been invoked to uncover simplicity bias in GP maps, an exponentially decaying upper bound in phenotype probability with the increasing phenotype descriptional complexity. This means that phenotypes with many genotypes assigned via the GP map must be simple, while complex phenotypes must have few genotypes assigned. Here, we use similar arguments to bound the probability P(x → y) that phenotype x, upon random genetic mutation, transitions to phenotype y. The bound is P(x→y)≲2^{−aK~(y|x)−b} , where K~(y|x) is the estimated conditional complexity of y given x, quantifying how much extra information is required to make y given access to x. This upper bound is related to the conditional form of algorithmic probability from AIT. We demonstrate the practical applicability of our derived bound by predicting phenotype transition probabilities (and other related quantities) in simulations of RNA and protein secondary structures. Our work contributes to a general mathematical understanding of GP maps and may facilitate the prediction of transition probabilities directly from examining phenotype themselves, without utilizing detailed knowledge of the GP map.

Abstract:

Fitness landscapes are often described in terms of 'peaks' and 'valleys', indicating an intuitive low-dimensional landscape of the kind encountered in everyday experience. The space of genotypes, however, is extremely high dimensional, which results in counter-intuitive structural properties of genotype-phenotype maps. Here we show that these properties, such as the presence of pervasive neutral networks, make fitness landscapes navigable. For three biologically realistic genotype-phenotype map models-RNA secondary structure, protein tertiary structure and protein complexes-we find that, even under random fitness assignment, fitness maxima can be reached from almost any other phenotype without passing through fitness valleys. This in turn indicates that true fitness valleys are very rare. By considering evolutionary simulations between pairs of real examples of functional RNA sequences, we show that accessible paths are also likely to be used under evolutionary dynamics. Our findings have broad implications for the prediction of natural evolutionary outcomes and for directed evolution.