{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:57:29Z","timestamp":1790668649247,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P41GM103533"],"award-info":[{"award-number":["P41GM103533"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM094306"],"award-info":[{"award-number":["R01GM094306"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1120425"],"award-info":[{"award-number":["1120425"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["T32 HG000035"],"award-info":[{"award-number":["T32 HG000035"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Experimental evolution provides a reproducible testing ground for the study of adaptive evolution where the numerous degrees of freedom impacting the trajectory of evolution can be limited to their most controlled form. Evolution in a continuous culture device known as the chemostat further constrains the variables that introduce stochasticity by maintaining constant selective pressure and environmental conditions. Using a multiplexed miniature chemostat setup, we generated a highly parallel set of yeast evolution experiments in glucose-, phosphate-, and sulfate-limited media conditions with a total of 95 replicates across the conditions. Whole genome sequencing of the resulting populations allowed us to analyze recurrent targets of mutation during these evolution experiments. Integrating the mutations observed here with previously generated data, we found consistent targeting of complexes and pathways, such as the SAGA complex in sulfate limitation, the sirtuin family in phosphate limitation, and the phosphorelay signal transduction system in glucose limitation. We also recurrently observed new mobilizations of Ty1 and Ty2 transposable elements, often interrupting genes that were also separately mutated by SNPs\/InDels in other populations. Comparing the frequency of genes impacted by either SNPs and indels or Ty1\/Ty2 elements, we find that a gene's location relative to predictors of Ty element mobilization likely impacted whether a gene was affected by either mutational modality. Overall, we identify how the biases in mutational frequency and the effect of local genome context can impact the direction of evolution and shape the path a population takes across the fitness landscape.<\/jats:p>","DOI":"10.1093\/genetics\/iyag238","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:34:34Z","timestamp":1790667274000},"source":"Crossref","is-referenced-by-count":0,"title":["Mutational bias and local genome context constrain adaptive paths in experimental evolution"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5732-970X","authenticated-orcid":false,"given":"Christopher R L","family":"Large","sequence":"first","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19146 ,","place":["United States"]},{"name":"Department of Biology, University of Pennsylvania , Philadelphia, PA 19146 ,","place":["United States"]},{"name":"Department of Genome Sciences, University of Washington , Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron W","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Washington , Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryony","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Washington , Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Washington , Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Washington , Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9944-2666","authenticated-orcid":false,"given":"Maitreya J","family":"Dunham","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Washington , Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"2026092903342838700_iyag238-B1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-88","article-title":"Whole-genome sequencing of a laboratory-evolved yeast strain","volume":"11","author":"Araya","year":"2010","journal-title":"BMC Genomics"},{"key":"2026092903342838700_iyag238-B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/bies.201600176","article-title":"What drives parallel evolution?: how population size and mutational variation contribute to repeated evolution","volume":"39","author":"Bailey","year":"2017","journal-title":"Bioessays"},{"key":"2026092903342838700_iyag238-B3","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1101\/gr.129585.111","article-title":"A nucleosomal surface defines an integration hotspot for the Saccharomyces cerevisiae Ty1 retrotransposon","volume":"22","author":"Baller","year":"2012","journal-title":"Genome Res"},{"key":"2026092903342838700_iyag238-B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002016","article-title":"Origin-dependent inverted-repeat amplification: a replication-based model for generating palindromic amplicons","volume":"7","author":"Brewer","year":"2011","journal-title":"PLoS Genet"},{"key":"2026092903342838700_iyag238-B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005699","article-title":"Origin-dependent inverted-repeat amplification: tests of a model for inverted DNA amplification","volume":"11","author":"Brewer","year":"2015","journal-title":"PLoS Genet"},{"key":"2026092903342838700_iyag238-B6","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1126\/science.1259114","article-title":"An RNA polymerase III subunit determines sites of retrotransposon integration","volume":"348","author":"Bridier-Nahmias","year":"2015","journal-title":"Science"},{"key":"2026092903342838700_iyag238-B7","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1093\/oxfordjournals.molbev.a026009","article-title":"Multiple duplications of yeast hexose transport genes in response to selection in a glucose-limited environment","volume":"15","author":"Brown","year":"1998","journal-title":"Mol Biol Evol"},{"key":"2026092903342838700_iyag238-B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2119720119","article-title":"Mutation bias shapes the spectrum of adaptive substitutions","volume":"119","author":"Cano","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026092903342838700_iyag238-B9","doi-asserted-by":"publisher","first-page":"2831","DOI":"10.1093\/molbev\/msab073","article-title":"Asexual experimental evolution of yeast does not curtail transposable elements","volume":"38","author":"Chen","year":"2021","journal-title":"Mol Biol Evol"},{"key":"2026092903342838700_iyag238-B10","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.98934","article-title":"Template switching during DNA replication is a prevalent source of adaptive gene amplification","volume":"13","author":"Chuong","year":"2025","journal-title":"Elife"},{"key":"2026092903342838700_iyag238-B11","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.ygeno.2014.09.015","article-title":"The enduring utility of continuous culturing in experimental evolution","volume":"104","author":"Gresham","year":"2014","journal-title":"Genomics"},{"key":"2026092903342838700_iyag238-B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000303","article-title":"The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast","volume":"4","author":"Gresham","year":"2008","journal-title":"PLoS Genet"},{"key":"2026092903342838700_iyag238-B13","doi-asserted-by":"publisher","first-page":"18551","DOI":"10.1073\/pnas.1014023107","article-title":"Adaptation to diverse nitrogen-limited environments by deletion or extrachromosomal element formation of the GAP1 locus","volume":"107","author":"Gresham","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026092903342838700_iyag238-B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010747","article-title":"Paths to adaptation under fluctuating nitrogen starvation: the spectrum of adaptive mutations in Saccharomyces cerevisiae is shaped by retrotransposons and microhomology-mediated recombination","volume":"19","author":"Hays","year":"2023","journal-title":"PLoS Genet"},{"key":"2026092903342838700_iyag238-B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004041","article-title":"Molecular specificity, convergence and constraint shape adaptive evolution in nutrient-poor environments","volume":"10","author":"Hong","year":"2014","journal-title":"PLoS Genet"},{"key":"2026092903342838700_iyag238-B16","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1534\/genetics.116.198895","article-title":"Experimental evolution reveals favored adaptive routes to cell aggregation in yeast","volume":"206","author":"Hope","year":"2017","journal-title":"Genetics"},{"key":"2026092903342838700_iyag238-B17","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.001404","article-title":"Mutation bias and adaptation in bacteria","volume":"169","author":"Horton","year":"2023","journal-title":"Microbiology"},{"key":"2026092903342838700_iyag238-B18","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1038\/ng.280","article-title":"Molecular characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiae","volume":"40","author":"Kao","year":"2008","journal-title":"Nat Genet"},{"key":"2026092903342838700_iyag238-B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002848","article-title":"A high-resolution two-step evolution experiment in yeast reveals a shift from pleiotropic to modular adaptation","volume":"22","author":"Kinsler","year":"2024","journal-title":"PLoS Biol"},{"key":"2026092903342838700_iyag238-B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003972","article-title":"Whole genome, whole population sequencing reveals that loss of signaling networks is the major adaptive strategy in a constant environment","volume":"9","author":"Kvitek","year":"2013","journal-title":"PLoS Genet"},{"key":"2026092903342838700_iyag238-B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000069","article-title":"Single-cell copy number variant detection reveals the dynamics and diversity of adaptation","volume":"16","author":"Lauer","year":"2018","journal-title":"PLoS Biol"},{"key":"2026092903342838700_iyag238-B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010850","article-title":"Template switching between the leading and lagging strands at replication forks generates inverted copy number variants through hairpin-capped extrachromosomal DNA","volume":"20","author":"Martin","year":"2024","journal-title":"PLoS Genet"},{"key":"2026092903342838700_iyag238-B23","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.molcel.2013.03.004","article-title":"Quantitative, genome-wide analysis of eukaryotic replication initiation and termination","volume":"50","author":"McGuffee","year":"2013","journal-title":"Mol Cell"},{"key":"2026092903342838700_iyag238-B24","doi-asserted-by":"publisher","DOI":"10.3791\/50262","article-title":"Design and use of multiplexed chemostat arrays","volume":"72","author":"Miller","year":"2013","journal-title":"J Vis Exp"},{"key":"2026092903342838700_iyag238-B25","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1101\/gr.129460.111","article-title":"Retrotransposon Ty1 integration targets specifically positioned asymmetric nucleosomal DNA segments in tRNA hotspots","volume":"22","author":"Mularoni","year":"2012","journal-title":"Genome Res"},{"key":"2026092903342838700_iyag238-B26","doi-asserted-by":"publisher","first-page":"2763","DOI":"10.1534\/g3.117.043893","article-title":"McClintock: an integrated pipeline for detecting transposable element insertions in whole-genome shotgun sequencing data","volume":"7","author":"Nelson","year":"2017","journal-title":"G3 (Bethesda)"},{"key":"2026092903342838700_iyag238-B27","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.devcel.2013.04.007","article-title":"The yeast Alix homolog Bro1 functions as a ubiquitin receptor for protein sorting into multivesicular endosomes","volume":"25","author":"Pashkova","year":"2013","journal-title":"Dev Cell"},{"key":"2026092903342838700_iyag238-B28","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1534\/g3.113.009365","article-title":"The dynamics of diverse segmental amplifications in populations of Saccharomyces cerevisiae adapting to strong selection","volume":"4","author":"Payen","year":"2014","journal-title":"G3 (Bethesda)"},{"key":"2026092903342838700_iyag238-B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006339","article-title":"High-throughput identification of adaptive mutations in experimentally evolved yeast populations","volume":"12","author":"Payen","year":"2016","journal-title":"PLoS Genet"},{"key":"2026092903342838700_iyag238-B30","doi-asserted-by":"publisher","first-page":"W83","DOI":"10.1093\/nar\/gkw199","article-title":"G:Profiler-a web server for functional interpretation of gene lists (2016 update)","volume":"44","author":"Reimand","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2026092903342838700_iyag238-B31","doi-asserted-by":"publisher","first-page":"e31","DOI":"10.1158\/0008-5472.CAN-17-0337","article-title":"Variant review with the integrative genomics viewer","volume":"77","author":"Robinson","year":"2017","journal-title":"Cancer Res"},{"key":"2026092903342838700_iyag238-B32","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1111\/mec.14794","article-title":"The impact of transposable elements in adaptive evolution","volume":"28","author":"Schrader","year":"2019","journal-title":"Mol Ecol"},{"key":"2026092903342838700_iyag238-B33","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1534\/genetics.115.185165","article-title":"Heterozygote advantage is a common outcome of adaptation in Saccharomyces cerevisiae","volume":"203","author":"Sellis","year":"2016","journal-title":"Genetics"},{"key":"2026092903342838700_iyag238-B34","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1093\/molbev\/msx098","article-title":"Loss of heterozygosity drives adaptation in hybrid yeast","volume":"34","author":"Smukowski Heil","year":"2017","journal-title":"Mol Biol Evol"},{"key":"2026092903342838700_iyag238-B35","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1093\/molbev\/msx180","article-title":"Mutational biases influence parallel adaptation","volume":"34","author":"Stoltzfus","year":"2017","journal-title":"Mol Biol Evol"},{"key":"2026092903342838700_iyag238-B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002155","article-title":"The fitness consequences of aneuploidy are driven by condition-dependent gene effects","volume":"13","author":"Sunshine","year":"2015","journal-title":"PLoS Biol"},{"key":"2026092903342838700_iyag238-B37","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1126\/science.1212986","article-title":"The molecular diversity of adaptive convergence","volume":"335","author":"Tenaillon","year":"2012","journal-title":"Science"},{"key":"2026092903342838700_iyag238-B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002202","article-title":"Hunger artists: yeast adapted to carbon limitation show trade-offs under carbon sufficiency","volume":"7","author":"Wenger","year":"2011","journal-title":"PLoS Genet"},{"key":"2026092903342838700_iyag238-B39","doi-asserted-by":"publisher","DOI":"10.3791\/50168","article-title":"The use of chemostats in microbial systems biology","volume":"80","author":"Ziv","year":"2013","journal-title":"J Vis Exp"}],"container-title":["GENETICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/genetics\/advance-article-pdf\/doi\/10.1093\/genetics\/iyag238\/71456869\/iyag238.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/genetics\/advance-article-pdf\/doi\/10.1093\/genetics\/iyag238\/71456869\/iyag238.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:34:35Z","timestamp":1790667275000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/genetics\/advance-article\/doi\/10.1093\/genetics\/iyag238\/8844021"}},"subtitle":[],"editor":[{"given":"C","family":"Landry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":39,"URL":"https:\/\/doi.org\/10.1093\/genetics\/iyag238","relation":{},"ISSN":["1943-2631"],"issn-type":[{"value":"1943-2631","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"article-number":"iyag238"}}