Predicting evolutionary outcomes through the probability of accessing sequence variants

Natural selection can only operate on available genetic variation. Thus, determining the probability of accessing different sequence variants from a starting sequence can help predict evolutionary trajectories and outcomes. We define the concept of variant accessibility as the probability that a set of genotypes encoding a particular protein function will arise through mutations before subject to natural selection. This probability is shaped by the mutational biases of nucleotides and the structure of the genetic code. Using the influenza A virus as a model, we discuss how a more accessible but less fit variant can emerge as an adaptation rather than a more fit variant. We describe a genotype-accessibility landscape, complementary to the genotype-fitness landscape, that informs the likelihood of a starting sequence reaching different parts of genotype space. The proposed framework lays the foundation for predicting the emergence of adaptive genotypes in evolving systems such as viruses and tumors.

Automated summary

Determining the probability of accessing different sequence variants from a starting sequence can help predict evolutionary trajectories and outcomes. Variant accessibility is influenced by mutational biases and the genetic code's structure. The emergence of a less fit but more accessible variant as adaptation is discussed using influenza A virus as a model. The proposed genotype-accessibility landscape allows predicting the emergence of adaptive genotypes in evolving systems.