{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T13:53:08Z","timestamp":1776001988752,"version":"3.50.1"},"posted":{"date-parts":[[2025,5,3]]},"group-title":"Genetics","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,3]]},"abstract":"<jats:p>\n                  Purifying selection that limits the transmission of harmful mitochondrial DNA (mtDNA) mutations has been observed in both human and animal models. Yet the precise mechanism underlying this process remains undefined. Here, we present a highly specific and efficient\n                  <jats:italic>in situ<\/jats:italic>\n                  imaging method capable of visualizing mtDNA variants that differ by only a few nucleotides at single-molecule resolution in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  ovaries. Using this method, we revealed that selection primarily occurs within a narrow developmental window during germline cysts differentiation. At this stage, the proportion of the deleterious mtDNA variant decreases without a reduction in its absolute copy number. Instead, the healthier mtDNA variant replicates more frequently, thereby outcompeting the co-existing deleterious variant. These findings provide direct evidence that mtDNA selection is driven by replication competition rather than active elimination processes, shedding light on a fundamental yet previously unresolved mechanism governing mitochondrial genome transmission.\n                <\/jats:p>","DOI":"10.1101\/2025.04.29.650984","type":"posted-content","created":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T01:45:18Z","timestamp":1746323118000},"source":"Crossref","is-referenced-by-count":0,"title":["Replication competition drives the selective mtDNA inheritance in\n                  <i>Drosophila<\/i>\n                  ovary"],"prefix":"10.64898","author":[{"given":"Cheng","family":"Zhang","sequence":"first","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2705-1970","authenticated-orcid":false,"given":"Hansong","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1423-1809","authenticated-orcid":false,"given":"Hong","family":"Xu","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041206351952000_2025.04.29.650984v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.09.011"},{"key":"2026041206351952000_2025.04.29.650984v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a111480"},{"key":"2026041206351952000_2025.04.29.650984v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(78)90269-3"},{"key":"2026041206351952000_2025.04.29.650984v1.4","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.015321"},{"key":"2026041206351952000_2025.04.29.650984v1.5","first-page":"2001","article-title":"Single-molecule mitochondrial DNA imaging reveals heteroplasmy dynamics shaped by developmental bottlenecks and selection in different organs in vivo","volume":"2025","year":"2025","journal-title":"bioRxiv"},{"key":"2026041206351952000_2025.04.29.650984v1.6","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-11-1513"},{"key":"2026041206351952000_2025.04.29.650984v1.7","doi-asserted-by":"crossref","unstructured":"Chen Z , Wang ZH , Zhang GF , Bleck CKE , Chung DJ , Madison GP , Lindberg E , Combs C , Balaban RS , Xu H (2020) Mitochondrial DNA segregation and replication restrict the transmission of detrimental mutation. 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