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Rates of repeat evolution differ between and within species and are likely modulated by both genetics and environment. To uncover factors shaping the rate of genome content evolution, we analyzed 1043 resequenced\n                    <jats:italic>Arabidopsis thaliana<\/jats:italic>\n                    genomes using a novel K-mer-based approach to characterize genome content variation and identify hypervariable regions underlying differences in repeat abundance. We next treated repeat abundance as a quantitative trait and performed genome-wide association analyses across more than 400 repeat families to identify the genetic basis of copy number variation. Integrating these results through a meta-GWAS approach revealed both cis-acting variants and more than 50 candidate trans-acting loci associated with repeat abundance genome-wide. Cis-acting variation was predominantly localized to pericentromeric and centromeric regions, whereas trans-acting loci were enriched for candidate genes involved in DNA replication, DNA repair, and DNA methylation regulation. The results are consistent with purifying selection acting against mutations that accelerate genome content divergence, favoring alleles that constrain repeat expansion. Together, these findings provide new insights into the genetic architecture and evolutionary forces shaping genome evolution in\n                    <jats:italic>A. thaliana<\/jats:italic>\n                    and establish a framework for investigating these processes in other plant species.\n                  <\/jats:p>","DOI":"10.7554\/elife.108238","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:30:45Z","timestamp":1761057045000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.108238","source":"Crossref","is-referenced-by-count":0,"title":["The genetic control of rapid genome content divergence in Arabidopsis thaliana"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9569-1809","authenticated-orcid":true,"given":"Christopher J","family":"Fiscus","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Botany and Plant Sciences, University of California","place":["Riverside, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1037-5346","authenticated-orcid":true,"given":"Daniel","family":"Koenig","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Botany and Plant Sciences, University of California","place":["Riverside, United States"]},{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Integrative Genome Biology, University of California","place":["Riverside, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1126\/science.287.5461.2185","type":"journal-article","article-title":"The genome sequence of Drosophila melanogaster","volume":"287","author":"Adams","year":"2000","journal-title":"Science"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-2-r18","type":"journal-article","article-title":"Analyzing and minimizing PCR amplification bias in Illumina sequencing libraries","volume":"12","author":"Aird","year":"2011","journal-title":"Genome Biology"},{"key":"bib3","type":"software","article-title":"TopGO: enrichment analysis for gene ontology","volume-title":"R Package","author":"Alexa","year":"2019","unstructured":"Alexa A, Rahnenfuhrer J. 2019. 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