Super compensatory substitutions restore protein function and flatten fitness landscapes

Wenhong Jiang1,5† *, Hengchuang Yin2,5†, Saad S. Khan3,5†, Yiparemu4 and Lucas B. Carey5,6* 1 Key Laboratory of Fermentation Engineering (Ministry of Education), National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China 2 Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Science, Urumqi, China 3 Departments of Bioengineering, Biology, Chemistry and Chemical Biology, Single Cell Proteomics Center, and Barnett Institute, Northeastern University, Boston, MA 02115, US 4 Henan University School of Stomatology, Kaifeng, China 5 Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China 6 Pando Bioscience, Watertown, MA. Codes: scripts MakeRescuabilityFile.py ##generate the rescuability files MakeSingleSiteRescuabilityFile.py ## calculate the rescuability for each site of His3p MakeSingleSiteConservationFile.py ##calculate the conservation score for each site of His3p MakeFeaturePredictFitnessFile.py ##generate the correlation files that AAindex value of amino acids can predict fitness MakeSubsCompensateAlleles.py ##detect super compensators MakeSCBufferingAbility.py ##generate the files that super compensator can buffer the fitness landscape MaskesuperCompensators_multipleDMSdata.py ##detect super compensators from other public DMS data MaskesuperCompensator_analysis_skwness_multipleDMSdata.py ##evaluate if super compensators from other public DMS data can reduce fitness effects File:files Original_SData ##fitness for each variant RescuabilityFile ##the rescuability files RSAWCNConservationInterfaceFile ##RSA/WCN/Conservation score of each site of His3p EnergyCalculationVariants ##the △△G for variants FeaturePredictFitness ##files that AAindex value of amino acid can predict fitness SuperCompensationFile ##super compensators DeepLearningWeights ##files of fitness impact score of each allele CoexsitAlleleinSpecies ##files that super compensators can co-exist with other deleterious alleles Makefile:the main script to generate files by running the scripts in Codes