Epistasis articles within Nature Communications

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  • Article
    | Open Access

    Reynolds and colleagues examine a biochemically-mediated epistatic interaction between metabolic enzymes involved in folate metabolism and show that biochemical coupling shapes the range of enzyme activities sufficient to rescue cell growth.

    • Thuy N. Nguyen
    • , Christine Ingle
    •  & Kimberly A. Reynolds

  • Article
    | Open Access

    Here, the authors perform statistical analyses to demonstrate that epistasis is highly pervasive in adaptive evolutionary trajectories of enzymes. Using epistatic data, they expose higher-order rewiring of intramolecular amino acid networks.

    • Karol Buda
    • , Charlotte M. Miton
    •  & Nobuhiko Tokuriki

  • Article
    | Open Access

    Global epistasis can be used to reconstruct fitness landscapes and infer adaptive trajectories. Here, the authors investigate how environmental variation impacts patterns of global epistasis, finding that global epistasis in the malaria parasite P. falciparum can be modulated by drug concentration in the environment.

    • Juan Diaz-Colunga
    • , Alvaro Sanchez
    •  & C. Brandon Ogbunugafor

  • Article
    | Open Access

    Alterations in oncogenes and tumor suppressor genes are a hallmark of cancer, yet how they interact remains poorly understood. Here, the authors describe a quantitative functional cancer genomics platform in genetically engineered mice, and uncover complex interactions between tumor suppressors and KRAS, BRAF, and EGFR oncogenes across more than 100 different lung tumor genotypes.

    • Lily M. Blair
    • , Joseph M. Juan
    •  & Ian P. Winters

  • Article
    | Open Access

    Fitness landscapes largely shape the dynamics of evolution, but it is unclear how they shift upon ecological diversification. By engineering genome-wide knockout libraries of a nascent bacterial community, Ascensao et al. show how ecological and epistatic patterns combine to shape adaptive landscapes.

    • Joao A. Ascensao
    • , Kelly M. Wetmore
    •  & Oskar Hallatschek

  • Article
    | Open Access

    The bacterium E. coli has around 300 transcriptional factors, but the functions of many of them, and the interactions between their respective regulatory networks, are unclear. Here, the authors study genetic interactions among all transcription factor genes in E. coli, revealing condition-dependent interactions and roles for uncharacterized transcription factors.

    • Alla Gagarinova
    • , Ali Hosseinnia
    •  & Mohan Babu

  • Article
    | Open Access

    Epistasis can lead to different phenotypic consequences from the same mutation. Here the authors carry out a genome-wide analysis of conditionally essential genes in yeast, finding that gene essentiality changes tend to occur concordantly among components of the same protein complex or metabolic pathway.

    • Piaopiao Chen
    • , Agnès H. Michel
    •  & Jianzhi Zhang

  • Article
    | Open Access

    Heritable traits can be affected by additive, dominance, and epistatic effects at genetic loci. Here, the authors use chromosomally-encoded barcodes to perform linkage mapping in diploid cross progeny in budding yeast, finding that epistasis in diploids frequently modifies both additivity and dominance.

    • Takeshi Matsui
    • , Martin N. Mullis
    •  & Ian M. Ehrenreich

  • Article
    | Open Access

    Studying the contribution of pairs of genes to complex traits has been challenging. Here, the authors combine exome and genotype data with RNAi to screen for genetic interactions between 30 genes identified in lipid GWAS to hint at pairs whose joint modulation may improve lipid-lowering therapies.

    • Magdalena Zimoń
    • , Yunfeng Huang
    •  & Heiko Runz

  • Article
    | Open Access

    In quantitative genetics, it is widely assumed that mutations combine additively or epistasis can be predicted with statistical or mechanistic models. Here, the authors use the phage lambda repressor model to show how biophysical ambiguity and non-monotonic functions confound phenotypic prediction.

    • Xianghua Li
    •  & Ben Lehner

  • Article
    | Open Access

    Phosphatidylinositol 3-kinase catalyzes the reaction from PI(4,5)P2 to PI(3,4,5)P3 and is encoded by the age-1 gene known to regulate lifespan. Here the researchers found that the metabolite myo-inositol, which can be converted to PI(3,4,5)P3 extends worm lifespan and alleviates worm as well as mouse health decline during aging.

    • Dawei Shi
    • , Xian Xia
    •  & Jing-Dong J. Han

  • Article
    | Open Access

    High-throughput combinatorial mutagenesis assays are useful to screen the function of many different sequences but they are not exhaustive. Here, Zhou and McCandlish develop a method to impute such missing genotype-phenotype data based on inferring the least epistatic sequence-function relationship.

    • Juannan Zhou
    •  & David M. McCandlish

  • Article
    | Open Access

    A difference in the survival of respiratory chain complex III deficient Bcs1lp.S78G mice was observed between two congenic mouse strains. Here the authors show how in one of the strains the combined effects of a spontaneously arising non-pathogenic variant and the disease-causing Bcs1lp.S78G mutation exacerbate CIII deficiency and disease progression.

    • Janne Purhonen
    • , Vladislav Grigorjev
    •  & Jukka Kallijärvi

  • Article
    | Open Access

    Epistasis underlies the complexity of genotype-phenotype maps. Here, the authors analyze 8,192 mutants that link two phenotypically distinct variants of the Entacmaea quadricolor fluorescent protein, and show the existence, but also the sparsity, of high-order epistatic interactions.

    • Frank J. Poelwijk
    • , Michael Socolich
    •  & Rama Ranganathan

  • Article
    | Open Access

    Non-additive genetic interactions are plastic and can complicate genetic prediction. Here, using deep mutagenesis of the lambda repressor, Li et al. reveal that changes in gene expression can alter the strength and direction of genetic interactions between mutations in many genes and develop mathematical models for predicting them.

    • Xianghua Li
    • , Jasna Lalić
    •  & Ben Lehner

  • Article
    | Open Access

    Studying how genetic variants in different genes interact and their combinatorial output is experimentally and analytically challenging. Here, the authors quantify the effects of more than 5000 mutation pairs in the yeast GAL regulatory system, finding that many combinations can be predicted with statistical models.

    • Aaron M. New
    •  & Ben Lehner

  • Article
    | Open Access

    Autophagic activity decreases with age via unknown mechanisms. Here the authors show that expression of the negative autophagy regulator Rubicon increases with age, that its genetic ablation improves lifespan and ameliorates a number of age-associated phenotypes in invertebrates and in mouse models.

    • Shuhei Nakamura
    • , Masaki Oba
    •  & Tamotsu Yoshimori

  • Article
    | Open Access

    Mutations often show distinct phenotypic effects across different genetic backgrounds. Here the authors describe the genetic basis of these so-called background effects using data on genotype and growth in 10 environments from 1411 segregants from a cross of two strains of budding yeast.

    • Martin N. Mullis
    • , Takeshi Matsui
    •  & Ian M. Ehrenreich

  • Article
    | Open Access

    Dissecting the architecture of complex trait is challenging. Here, Hallin, Märtens et al. devises Phased Outbred Lines (POLs) in order to accurately decompose growth trait variation in diploid yeast across different environments.

    • Johan Hallin
    • , Kaspar Märtens
    •  & Gianni Liti

  • Article
    | Open Access

    Ankylosing spondylitis is a common, highly inheritable inflammatory arthritis with poorly understood biology. Here Brown, Cortes and colleagues use fine mapping of the major histocompatibility complex and identify novel associations, and identify other HLA alleles that like HLA-B27 interact with ERAP1 variants to influence disease risk.

    • Adrian Cortes
    • , Sara L. Pulit
    •  & Matthew A. Brown

  • Article
    | Open Access

    Terpene cyclases are ring-forming enzymes found in many biosynthetic pathways, but the evolutionary origins of the cyclization mechanism is not well understood. Here, the authors use structure-guided breeding to identify an epistatic network that controls the onset of cyclization activity in Artemisia annua.

    • Melissa Salmon
    • , Caroline Laurendon
    •  & Paul E. O’Maille

  • Article |

    Cancer can result from mutations in more than one gene and these multiple mutated genes are often functionally dependent on each other; this interaction is known as epistasis. Here, the authors use a combinatorial RNAi screen to identify epistatic genes that are mutated in breast cancer and reveal large numbers of previously unreported gene interactions.

    • Xiaoyue Wang
    • , Audrey Q. Fu
    •  & Kevin P. White

  • Article |

    Mutations are the source of genetic variation, yet the mechanisms determining the distribution of mutations are unclear. Here, Jones et al.show that gene interactions allow natural selection to shape the distribution of mutations, suggesting that mutations can be a biased source of genetic variation.

    • Adam G. Jones
    • , Reinhard Bürger
    •  & Stevan J. Arnold

  • Article |

    It is unclear how interactions between individual genomes affect behaviour and survival in social organisms. Here, Teseo et al. show that genomic interactions between larvae and nursing adults of the clonal ant Cerapachys biroidetermine the proportion of individuals involved in reproduction or cooperation.

    • Serafino Teseo
    • , Nicolas Châline
    •  & Daniel J.C. Kronauer

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