Predicting evolutionary outcomes through the probability of accessing sequence variants.

Sci Adv

MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.

Published: July 2023

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381947PMC
http://dx.doi.org/10.1126/sciadv.ade2903DOI Listing

Publication Analysis

Top Keywords

probability accessing
8
accessing sequence
8
sequence variants
8
natural selection
8
starting sequence
8
fit variant
8
predicting evolutionary
4
evolutionary outcomes
4
probability
4
outcomes probability
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!