Clonal Heterogeneity Influences the Fate of New Adaptive Mutations

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dc.contributor.authorVazquez-Garcia, Ignacio
dc.contributor.authorSalinas, Francisco
dc.contributor.authorLi, Jing
dc.contributor.authorFischer, Andrej
dc.contributor.authorBarre, Benjamin
dc.contributor.authorHallin, Johan
dc.contributor.authorBergstrom, Anders
dc.contributor.authorAlonso-Perez, Elisa
dc.contributor.authorWarringer, Jonas
dc.contributor.authorMustonen, Ville
dc.contributor.authorLiti, Gianni
dc.date.accessioned2025-01-23T21:25:03Z
dc.date.available2025-01-23T21:25:03Z
dc.date.issued2017
dc.description.abstractThe joint contribution of pre-existing and de novo genetic variation to clonal adaptation is poorly understood but essential to designing successful antimicrobial or cancer therapies. To address this, we evolve genetically diverse populations of budding yeast, S. cerevisiae, consisting of diploid cells with unique haplotype combinations. We study the asexual evolution of these populations under selective inhibition with chemotherapeutic drugs by time-resolved whole-genome sequencing and phenotyping. All populations undergo clonal expansions driven by de novo mutations but remain genetically and phenotypically diverse. The clones exhibit widespread genomic instability, rendering recessive de novo mutations homozygous and refining pre-existing variation. Finally, we decompose the fitness contributions of pre-existing and de novo mutations by creating a large recombinant library of adaptive mutations in an ensemble of genetic backgrounds. Both pre-existing and de novo mutations substantially contribute to fitness, and the relative fitness of preexisting variants sets a selective threshold for new adaptive mutations.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.celrep.2017.09.046
dc.identifier.issn2211-1247
dc.identifier.urihttps://doi.org/10.1016/j.celrep.2017.09.046
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101321
dc.identifier.wosidWOS:000413090600015
dc.issue.numero3
dc.language.isoen
dc.pagina.final744
dc.pagina.inicio732
dc.revistaCell reports
dc.rightsacceso restringido
dc.subject.ods13 Climate Action
dc.subject.odspa13 Acción por el clima
dc.titleClonal Heterogeneity Influences the Fate of New Adaptive Mutations
dc.typeartículo
dc.volumen21
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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