Epistatic hotspots organize antibody fitness landscape and boost evolvability.

ABSTRACT: The course of evolution is strongly shaped by interaction between mutations. Such epistasis can yield rugged sequence-function maps and constrain the availability of adaptive paths. While theoretical intuition is often built on global statistics of large, homogeneous model landscapes, mutagenesis measurements necessarily probe a limited neighborhood of a reference genotype. It is unclear to what extent local topography of a real epistatic landscape represents its global shape. Here, we demonstrate that epistatic landscapes can be heterogeneously rugged and this heterogeneity may render biomolecules more evolvable. By characterizing a multipeaked fitness landscape of a SARS-CoV-2 antibody mutant library, we show that heterogeneous ruggedness arises from sparse epistatic hotspots, whose muta

SUBMITTER: Schulz S 

PROVIDER: S-EPMC11745389 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature