Robustness of ancestral sequence reconstruction to among-site evolutionary heterogeneity and epistasis.

ABSTRACT: Ancestral sequence reconstruction (ASR) is typically performed using homogeneous evolutionary models, which assume that the same substitution propensities affect all sites and lineages. These assumptions are routinely violated: heterogeneous structural and functional constraints favor different amino acid states at different sites, and these constraints often change among lineages as epistatic substitutions accrue at other sites. To evaluate how realistic violations of the homogeneity assumption affect ASR, we developed site-specific substitution models and parameterized them using data from deep mutational scanning experiments on three protein families; we then used these models to perform ASR on the empirical alignments and on alignments simulated under heterogeneous conditions derived f

SUBMITTER: Muniz-Trejo R 

PROVIDER: S-EPMC11702759 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature