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    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima

    Ekaterina Morgunova et al.
    The epistasis observed in TF-DNA binding preferences can be explained by the presence of two optima of very similar Gibbs energy that are located relatively far from each other in sequence space.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Genetic interactions affecting human gene expression identified by variance association mapping

    Andrew Anand Brown et al.
    Multiple replicated examples of epistasis affecting gene expression in humans are identified, some explaining a substantial proportion of the variation in expression.
    1. Cell Biology
    2. Evolutionary Biology

    Evolutionary adaptation after crippling cell polarization follows reproducible trajectories

    Liedewij Laan et al.
    Deletion of one gene can lead to inactivation of other genes which restore a perturbed cellular function but change the epistatic interactions and the dynamics of the responsible module.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1

    Justin M Jenson et al.
    Short peptides that bind tightly to anti-apoptotic protein Bfl-1 but not other Bcl-2 family members provide a tool for diagnosing cancer cell survival mechanisms and a lead for developing new therapeutics.
    1. Evolutionary Biology
    2. Genetics and Genomics

    The role of structural pleiotropy and regulatory evolution in the retention of heteromers of paralogs

    Axelle Marchant et al.
    Regulatory evolution allows paralogs to escape from strucural pleiotropy.
    1. Evolutionary Biology

    Adaptation in protein fitness landscapes is facilitated by indirect paths

    Nicholas C Wu et al.
    The extra dimensions in protein sequence space open up indirect paths of adaptation and alleviate the constraint on the selective accessibility to high fitness genotypes.
    1. Biochemistry and Chemical Biology
    2. Evolutionary Biology

    Reverse evolution leads to genotypic incompatibility despite functional and active site convergence

    Miriam Kaltenbach et al.
    Enzyme evolution is reversible on a structural and functional (phenotypic) level, but through a different mutational pathway that leads to genotypic incompatibility with the ancestor.
    1. Computational and Systems Biology

    Inferring genetic interactions from comparative fitness data

    Kristina Crona et al.
    A new mathematical approach can infer higher order genetic interactions from pairwise fitness comparisons between genotypes.