2025
Applying multilevel selection to understand cancer evolution and progression
Laplane L, Lamoureux A, Richker H, Alcaraz G, Fortunato A, Shaffer Z, Aktipis A, Mischel P, Plutynski A, Townsend J, Maley C. Applying multilevel selection to understand cancer evolution and progression. PLOS Biology 2025, 23: e3003290. PMID: 40680084, PMCID: PMC12303392, DOI: 10.1371/journal.pbio.3003290.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological EvolutionCell ProliferationDisease ProgressionHumansNeoplasmsSelection, GeneticEvolutionarily divergent Mycobacterium tuberculosis CTP synthase filaments are under selective pressure
Lynch E, Lu Y, Park J, Shao L, Kollman J, Rego E. Evolutionarily divergent Mycobacterium tuberculosis CTP synthase filaments are under selective pressure. Nature Communications 2025, 16: 5993. PMID: 40593557, PMCID: PMC12219555, DOI: 10.1038/s41467-025-60847-6.Peer-Reviewed Original ResearchConceptsCytidine triphosphate synthaseChromosome segregationCytidine triphosphateClinical isolatesClinical isolates of M. tuberculosisHigher-order filamentsCell wall synthesisTree of lifeIsolates of M. tuberculosisM. tuberculosisMutant enzymesWall synthesisCritical nucleotidesPyrimidine biosynthesisPositive selectionSelection pressureHigher-order structureActive conformationFilament formationProduct inhibitionUnusual architectureChromosomeMycobacterium tuberculosisEnzymeCellular techniques
2023
BTG1 mutation yields supercompetitive B cells primed for malignant transformation
Mlynarczyk C, Teater M, Pae J, Chin C, Wang L, Arulraj T, Barisic D, Papin A, Hoehn K, Kots E, Ersching J, Bandyopadhyay A, Barin E, Poh H, Evans C, Chadburn A, Chen Z, Shen H, Isles H, Pelzer B, Tsialta I, Doane A, Geng H, Rehman M, Melnick J, Morgan W, Nguyen D, Elemento O, Kharas M, Jaffrey S, Scott D, Khelashvili G, Meyer-Hermann M, Victora G, Melnick A. BTG1 mutation yields supercompetitive B cells primed for malignant transformation. Science 2023, 379: eabj7412. PMID: 36656933, PMCID: PMC10515739, DOI: 10.1126/science.abj7412.Peer-Reviewed Original ResearchConceptsGerminal center B cellsPositive selection signalsB-cell fitnessCell fitnessUnicellular organismsB cellsMulticellular lifeNatural selectionSelection signalsInduction kineticsGatekeeper mechanismAdaptive immune systemAltruistic cooperationNew mouse modelNormal counterpartsHuman lymphomasAntibody affinity maturationCellsInvasive lymphomaClinical outcomesMouse modelImmune systemMalignant transformationSupercompetitorsAffinity maturation
2022
A general calculus of fitness landscapes finds genes under selection in cancers
Hsu TK, Asmussen J, Koire A, Choi BK, Gadhikar M, Huh E, Lin CH, Konecki D, Kim YW, Pickering C, Kimmel M, Donehower L, Frederick M, Myers JN, Katsonis P, Lichtarge O. A general calculus of fitness landscapes finds genes under selection in cancers. Genome Research 2022, 32: gr.275811.121. PMID: 35301263, PMCID: PMC9104707, DOI: 10.1101/gr.275811.121.Peer-Reviewed Original ResearchMeSH KeywordsBiological EvolutionCalculiGenetic FitnessGenotypeHumansModels, GeneticNeoplasmsPhenotypeSelection, GeneticConceptsEvolution of traitsFitness landscapeGenotype-phenotype relationshipsEvolutionary relationshipsComplex traitsPositive selectionGenomic searchSpecific traitsCancer InsightsGenesGenetic variantsFunctional impactTraitsExperimental supportLandscapeVariantsPhenotypeEvolutionSelectionGenotypesCancer cohort
2021
DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis
Laut C, Leasure C, Pi H, Carlin S, Chu M, Hillebrand G, Lin H, Yi X, Stauff D, Skaar E. DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis. Infection And Immunity 2021, 90: e00560-21. PMID: 34748369, PMCID: PMC8788696, DOI: 10.1128/iai.00560-21.Peer-Reviewed Original ResearchConceptsTwo-component systemGene expressionSubstrate-binding subunitSignal transduction activityTarget gene expressionB. anthracisBacillus anthracisGram-positive bacteriumHost-induced stressesClpXP proteaseProtein chaperonesSignal transductionClpXGene productsTransduction activityDnaJVertebrate hostsHeme levelsHomeostasis regulatorGenetic selectionHigh heme levelsCell envelope disruptionBioterror weaponHssRSAnthracisFluctuating Environments Maintain Genetic Diversity through Neutral Fitness Effects and Balancing Selection
Abdul-Rahman F, Tranchina D, Gresham D. Fluctuating Environments Maintain Genetic Diversity through Neutral Fitness Effects and Balancing Selection. Molecular Biology And Evolution 2021, 38: 4362-4375. PMID: 34132791, PMCID: PMC8476146, DOI: 10.1093/molbev/msab173.Peer-Reviewed Original ResearchMeSH KeywordsBiological EvolutionEnvironmentGenetic FitnessGenetic VariationGenotypeSelection, GeneticConceptsDistribution of fitness effectsNeutral fitness effectsGenetic diversityFitness effectsFluctuating environmentsMaintenance of genetic diversityGene deletion collectionHigh-fitness genotypesTemporally fluctuating environmentsShort-term fitnessVariable selection effectDynamics of selectionDeletion collectionBarcode sequencesFit genotypesNutrient limitationUnique genotypesGenetic variationContinuous cultureEvolutionary biologyEnvironmental fluctuationsDiversityEnvironmental conditionsGenotypesPopulation diversity
2020
Directed evolution reveals the mechanism of HitRS signaling transduction in Bacillus anthracis
Pi H, Chu M, Ivan S, Latario C, Toth A, Carlin S, Hillebrand G, Lin H, Reppart J, Stauff D, Skaar E. Directed evolution reveals the mechanism of HitRS signaling transduction in Bacillus anthracis. PLOS Pathogens 2020, 16: e1009148. PMID: 33362282, PMCID: PMC7790381, DOI: 10.1371/journal.ppat.1009148.Peer-Reviewed Original ResearchMeSH KeywordsBacillus anthracisBacterial ProteinsGene Expression Regulation, BacterialSelection, GeneticSignal TransductionStress, PhysiologicalConceptsHAMP domainSignal transductionGenetic selectionUnbiased genetic selectionCell envelope stressPathogen Bacillus anthracisSignal transduction systemImportant signal transduction systemMechanistic understandingBacillus anthracisComprehensive mechanistic understandingNumerous point mutationsEnvelope stressTransduction systemMolecular basisMutational analysisPoint mutationsTransductionRate-limiting stepIndividual domainsSpecific interactionsSignal sensingHITRAnthracisSystematic characterizationCharacterizing the effect of background selection on the polygenicity of brain-related traits
Wendt FR, Pathak GA, Overstreet C, Tylee DS, Gelernter J, Atkinson EG, Polimanti R. Characterizing the effect of background selection on the polygenicity of brain-related traits. Genomics 2020, 113: 111-119. PMID: 33278486, PMCID: PMC7855394, DOI: 10.1016/j.ygeno.2020.11.032.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesBrain-related traitsGWAS of schizophreniaTrait-associated lociLocus effect sizesSubset of traitsGenotype networksGenetic architectureIntolerant regionsBrain-related phenotypesBackground selectionNatural selectionEvolutionary pressurePositive selectionSNP heritabilityLocal ancestryAssociation studiesTraitsFunctional significanceLociPolygenicityBinary annotationPhenotypeRisk allelesSize varianceFunctional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats
Pyott SJ, van Tuinen M, Screven LA, Schrode KM, Bai JP, Barone CM, Price SD, Lysakowski A, Sanderford M, Kumar S, Santos-Sacchi J, Lauer AM, Park TJ. Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats. Current Biology 2020, 30: 4329-4341.e4. PMID: 32888484, PMCID: PMC8109146, DOI: 10.1016/j.cub.2020.08.035.Peer-Reviewed Original ResearchConceptsHair bundle morphologyAmino acid substitutionsAltered hearingLink proteinAcid substitutionsUnique evolutionary trajectoryMolecular evolutionary analysisCochlear amplificationEvolutionary characterizationEvolutionary analysisHuman hearing lossEvolutionary trajectoriesBundle morphologyPrestin functionAfrican Mole-RatsCodon levelSelection pressureSubterranean lifestyleSubterranean rodentsMole-RatUnique lifestyleProteinHair cellsSpeciesOuter hair cellsPervasive lesion segregation shapes cancer genome evolution
Aitken S, Anderson C, Connor F, Pich O, Sundaram V, Feig C, Rayner T, Lukk M, Aitken S, Luft J, Kentepozidou E, Arnedo-Pac C, Beentjes S, Davies S, Drews R, Ewing A, Kaiser V, Khamseh A, López-Arribillaga E, Redmond A, Santoyo-Lopez J, Sentís I, Talmane L, Yates A, Semple C, López-Bigas N, Flicek P, Odom D, Taylor M. Pervasive lesion segregation shapes cancer genome evolution. Nature 2020, 583: 265-270. PMID: 32581361, PMCID: PMC7116693, DOI: 10.1038/s41586-020-2435-1.Peer-Reviewed Original ResearchConceptsChromosome-scale phasingDNA lesionsAcquisition of oncogenic mutationsAlternative allelesGenetic diversityMultiple cell generationsCancer genomesLesion segregationDNA replicationMutagenic DNA lesionsDaughter cellsBase pairsCell divisionCell cycleExogenous mutagensHuman cellsOncogenic selectionOncogenic mutationsMouse liver tumorsDNACell generationDNA base pairsMutationsCellsGenomeWe shouldn’t worry when a virus mutates during disease outbreaks
Grubaugh ND, Petrone ME, Holmes EC. We shouldn’t worry when a virus mutates during disease outbreaks. Nature Microbiology 2020, 5: 529-530. PMID: 32071422, PMCID: PMC7095397, DOI: 10.1038/s41564-020-0690-4.Peer-Reviewed Original ResearchAdvances in the Evolutionary Understanding of MHC Polymorphism
Radwan J, Babik W, Kaufman J, Lenz T, Winternitz J. Advances in the Evolutionary Understanding of MHC Polymorphism. Trends In Genetics 2020, 36: 298-311. PMID: 32044115, DOI: 10.1016/j.tig.2020.01.008.Peer-Reviewed Original ResearchConceptsExcess of nonsynonymous changesMHC gene familyPathogen-driven selectionVertebrate adaptive immune responsePeptide-binding domainGene genealogiesAdaptive introgressionDeleterious mutationsGene familyNonsynonymous changesGeographic subdivisionMHC polymorphismMHC genesMHC allelesComplexity of selectionCell surfaceEvolutionary understandingImmune responseAdaptive immune responsesGenesPolymorphismPeptide antigensIntrogressionHitchhikingVertebratesGenome-Wide Natural Selection Signatures Are Linked to Genetic Risk of Modern Phenotypes in the Japanese Population
Yasumizu Y, Sakaue S, Konuma T, Suzuki K, Matsuda K, Murakami Y, Kubo M, Palamara P, Kamatani Y, Okada Y. Genome-Wide Natural Selection Signatures Are Linked to Genetic Risk of Modern Phenotypes in the Japanese Population. Molecular Biology And Evolution 2020, 37: 1306-1316. PMID: 31957793, PMCID: PMC7182208, DOI: 10.1093/molbev/msaa005.Peer-Reviewed Original ResearchMeSH KeywordsAsian PeopleGenome-Wide Association StudyGenome, HumanHumansMarkov ChainsPhenotypeSelection, GeneticConceptsSelection signaturesNatural selection signaturesTrait-associated variantsGenome-wide scanGenome-wide significanceAlcohol dehydrogenaseNatural selection studyPopulation-specific featuresAlcohol-related phenotypesAdaptive evolutionFine-mappingGenetic lociCluster locusUK Biobank ResourcePhenotypic dataHuman phenotypesSelection pressureJapanese populationEnrichment analysisPopulation-specific evidencePhenotypic spectrumPhenotypeBiobank ResourceGenetic riskImmune-related diseases
2019
Patterns, Mechanisms and Genetics of Speciation in Reptiles and Amphibians
Valero K, Marshall J, Bastiaans E, Caccone A, Camargo A, Morando M, Niemiller M, Pabijan M, Russello M, Sinervo B, Werneck F, Sites J, , Wiens J, Steinfartz S. Patterns, Mechanisms and Genetics of Speciation in Reptiles and Amphibians. Genes 2019, 10: 646. PMID: 31455040, PMCID: PMC6769790, DOI: 10.3390/genes10090646.Peer-Reviewed Original ResearchMeSH KeywordsAmphibiansAnimalsEcosystemEvolution, MolecularGenetic SpeciationReptilesSelection, GeneticConceptsEcological speciationSpeciation researchIntegrative taxonomyGenetics of speciationProcess of speciationSouth American lizardsSpeciation ratesPhenotypic evolutionEvolutionary forcesClimatic nicheEuropean salamandersPhenotypic traitsGenetic mechanismsEcological aspectsBiogeographyReptilesSpeciationAmphibiansCase studyGenomicsLizardsGeneticsTaxonomyFinal case studySalamanders
2018
Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia
Tucci S, Vohr SH, McCoy RC, Vernot B, Robinson MR, Barbieri C, Nelson BJ, Fu W, Purnomo GA, Sudoyo H, Eichler EE, Barbujani G, Visscher PM, Akey JM, Green RE. Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia. Science 2018, 361: 511-516. PMID: 30072539, PMCID: PMC6709593, DOI: 10.1126/science.aar8486.Peer-Reviewed Original ResearchConceptsPygmy populationsFlores IslandFADS Gene ClusterRecent positive selectionArchaic homininsModern humansSingle nucleotide polymorphism dataHominin speciesWhole genome sequencesInsular dwarfismComplex historyModern individualsMultiple independent instancesGene flowPolygenic selectionEvolutionary relationshipsEvolutionary historyGene clusterPositive selectionPolymorphism dataFloresShort stature phenotypeHistoryIslandsIndependent instancesNeutral Theory and the Somatic Evolution of Cancer
Cannataro VL, Townsend JP. Neutral Theory and the Somatic Evolution of Cancer. Molecular Biology And Evolution 2018, 35: 1308-1315. PMID: 29684198, PMCID: PMC5967571, DOI: 10.1093/molbev/msy079.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, BiologicalAnimalsEvolution, MolecularGenetic DriftHumansNeoplasmsSelection, GeneticAnalysis of Human Sequence Data Reveals Two Pulses of Archaic Denisovan Admixture
Browning SR, Browning BL, Zhou Y, Tucci S, Akey JM. Analysis of Human Sequence Data Reveals Two Pulses of Archaic Denisovan Admixture. Cell 2018, 173: 53-61.e9. PMID: 29551270, PMCID: PMC5866234, DOI: 10.1016/j.cell.2018.02.031.Peer-Reviewed Original ResearchCommon schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
Pardiñas A, Holmans P, Pocklington A, Escott-Price V, Ripke S, Carrera N, Legge S, Bishop S, Cameron D, Hamshere M, Han J, Hubbard L, Lynham A, Mantripragada K, Rees E, MacCabe J, McCarroll S, Baune B, Breen G, Byrne E, Dannlowski U, Eley T, Hayward C, Martin N, McIntosh A, Plomin R, Porteous D, Wray N, Caballero A, Geschwind D, Huckins L, Ruderfer D, Santiago E, Sklar P, Stahl E, Won H, Agerbo E, Als T, Andreassen O, Bækvad-Hansen M, Mortensen P, Pedersen C, Børglum A, Bybjerg-Grauholm J, Djurovic S, Durmishi N, Pedersen M, Golimbet V, Grove J, Hougaard D, Mattheisen M, Molden E, Mors O, Nordentoft M, Pejovic-Milovancevic M, Sigurdsson E, Silagadze T, Hansen C, Stefansson K, Stefansson H, Steinberg S, Tosato S, Werge T, GERAD1 Consortium, CRESTAR Consortium, Collier D, Rujescu D, Kirov G, Owen M, O’Donovan M, Walters J. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nature Genetics 2018, 50: 381-389. PMID: 29483656, PMCID: PMC5918692, DOI: 10.1038/s41588-018-0059-2.Peer-Reviewed Original ResearchConceptsMutation-intolerant genesGenetic architecture of schizophreniaGenome-wide association studiesChromosome conformation dataGenome fine mappingVariant association signalsAssociation signalsFine-mappingGenetic architectureCausal genesGenomic studiesAssociation studiesRisk variantsSelection pressureGenesLociBrain expressionAssociated with poor qualityBiologyConformational dataDecreased life expectancyChromosomeDebilitating psychiatric conditionAllelesLife expectancy
2017
Distributions of Mutational Effects and the Estimation of Directional Selection in Divergent Lineages of Arabidopsis thaliana
Park B, Rutter MT, Fenster CB, Symonds VV, Ungerer MC, Townsend JP. Distributions of Mutational Effects and the Estimation of Directional Selection in Divergent Lineages of Arabidopsis thaliana. Genetics 2017, 206: 2105-2117. PMID: 28550014, PMCID: PMC5560809, DOI: 10.1534/genetics.116.199190.Peer-Reviewed Original ResearchMeSH KeywordsArabidopsisEvolution, MolecularModels, GeneticMutation AccumulationQuantitative Trait LociSelection, GeneticConceptsMutation accumulation dataDirectional selectionNatural selectionMutational effectsPhenotypic traitsDirectional natural selectionQuantitative trait lociDivergent lineagesRosette diameterTrait lociHistorical selectionQuantitative traitsLineagesArabidopsisTraitsDensity traitsAccumulation dataDivergenceKey roleUltimate sourceLociSelectionOrganismsKey componentMutationsDetection of Regional Variation in Selection Intensity within Protein-Coding Genes Using DNA Sequence Polymorphism and Divergence
Zhao ZM, Campbell MC, Li N, Lee DSW, Zhang Z, Townsend JP. Detection of Regional Variation in Selection Intensity within Protein-Coding Genes Using DNA Sequence Polymorphism and Divergence. Molecular Biology And Evolution 2017, 34: 3006-3022. PMID: 28962009, PMCID: PMC5850860, DOI: 10.1093/molbev/msx213.Peer-Reviewed Original ResearchConceptsPoisson random fieldRandom fieldsEnsemble of modelsRandom field frameworkField frameworkClustering modelHistorical demographic trendsAmino acid-altering substitutionsSelection intensityEnsembleHigh powerUniform selectionProtein-coding genesProtein coding genesHeterogeneity of selectionDNA sequence polymorphismsComparison of polymorphisms
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply