The peculiar genetics of the ribosomal DNA blurs the boundaries of transgenerational epigenetic inheritance
- 99 Downloads
Our goal is to draw a line—hypothetical in its totality but experimentally supported at each individual step—connecting the ribosomal DNA and the phenomenon of transgenerational epigenetic inheritance of induced phenotypes. The reasonableness of this hypothesis is offset by its implication, that many (or most) (or all) of the cases of induced-and-inherited phenotypes that are seen to persist for generations are instead unmapped induced polymorphisms in the ribosomal DNA, and thus are the consequence of the peculiar and enduringly fascinating genetics of the highly transcribed repeat DNA structure at that locus.
KeywordsrDNA Ribosomal DNA Epigenetics
Bloom syndrome protein
Genome-wide association study
Long terminal repeat
Quantitative trait locus
Reverse transcription-quantitative polymerase chain reaction
Suppressor of variation
We gratefully acknowledge Drs. Pamela Geyer, C.-Ting Wu, and Harmit Malik for the encouragement.
Author contribution statement
FB and KAM wrote, read, and approved the manuscript.
The work was funded by an NIH Director’s Transformative Research Award (1R01GM123640), and support was provided by the UA. Cancer Center Core Grant (P30CA023074).
- Ashburner M, Golic KG, Hawley RS (2005) Drosophila: a laboratory handbook. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
- Beiko NN, Terekhov SM, Shubaeva NO, Simirnova TD, Ivanova SM et al (2005) Early and late responses to oxidative stress in human dermal fibroblasts of healthy donors and rheumatoid arthritis patients. Relationship between the cell death rate and the genomic dosage of active ribosomal genes. Mol Biol (Mosk) 39:264–275Google Scholar
- Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, Bock C, Li C, Gu H, Zamore PD, Meissner A, Weng Z, Hofmann HA, Friedman N, Rando OJ (2010) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143:1084–1096PubMedCentralCrossRefPubMedGoogle Scholar
- Daroit NB, Salgueiro AP, Maito F, Visioli F, Rados PV (2018) The use of cytopathology to identify disturbances in oral squamous cell carcinoma at early stage: a case report. Diagn CytopatholGoogle Scholar
- Holland ML, Lowe R, Caton PW, Gemma C, Carbajosa G, Danson AF, Carpenter AAM, Loche E, Ozanne SE, Rakyan VK (2016) Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice. In: Science, vol 353, pp 495–498Google Scholar
- Kim JH, Dilthey AT, Nagaraja R, Lee HS, Koren S, Dudekula D, Wood III WH, Piao Y, Ogurtsov AY, Utani K, Noskov VN, Shabalina SA, Schlessinger D, Phillippy AM, Larionov V (2018) Variation in human chromosome 21 ribosomal RNA genes characterized by TAR cloning and long-read sequencing. Nucleic Acids Res 46:6712–6725PubMedCentralCrossRefPubMedGoogle Scholar
- Kwan EX, Foss EJ, Tsuchiyama S, Alvino GM, Kruglyak L, Kaeberlein M, Raghuraman MK, Brewer BJ, Kennedy BK, Bedalov A (2013) A natural polymorphism in rDNA replication origins links origin activation with calorie restriction and lifespan. PLoS Genet 9:e1003329PubMedCentralCrossRefPubMedGoogle Scholar
- Lu KL, Nelson JO, Watase GJ, Warsinger-Pepe N, Yamashita YM (2018) Transgenerational dynamics of rDNA copy number in Drosophila male germline stem cells. Elife 7Google Scholar
- Muller HJ (1932) Further studies on the nature and causes of gene mutations. Proceedings of the 6th International Congress of Genetics: 213–255Google Scholar
- Pineiro D, Stoneley M, Ramakrishna M, Alexandrova J, Dezi V et al. (2018) Identification of the RNA polymerase I-RNA interactome. Nucleic Acids ResGoogle Scholar
- Pontes O, Lawrence RJ, Neves N, Silva M, Lee JH, Chen ZJ, Viegas W, Pikaard CS (2003) Natural variation in nucleolar dominance reveals the relationship between nucleolus organizer chromatin topology and rRNA gene transcription in Arabidopsis. Proc Natl Acad Sci U S A 100:11418–11423PubMedCentralCrossRefPubMedGoogle Scholar
- Sanij E, Poortinga G, Sharkey K, Hung S, Holloway TP, Quin J, Robb E, Wong LH, Thomas WG, Stefanovsky V, Moss T, Rothblum L, Hannan KM, McArthur GA, Pearson RB, Hannan RD (2008) UBF levels determine the number of active ribosomal RNA genes in mammals. J Cell Biol 183:1259–1274PubMedCentralCrossRefPubMedGoogle Scholar
- Spofford JB (1976) Position-effect variegation in Drosophila, pp. 955–1019 in The genetics and biology of Drosophila, edited by M. Ashburner and E. Novitski. Academic PressGoogle Scholar
- Terracol R, Iturbide Y, Prud'Homme N (1990) Partial reversion at the bobbed locus of Drosophila melanogaster. Biol Cell 68:65–71Google Scholar
- Udugama M, Sanij E, Voon HPJ, Son J, Hii L, Henson JD, Chan FL, Chang FTM, Liu Y, Pearson RB, Kalitsis P, Mann JR, Collas P, Hannan RD, Wong LH (2018) Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers. Proc Natl Acad Sci U S A 115:4737–4742PubMedCentralCrossRefPubMedGoogle Scholar
- van de Nobelen S, Rosa-Garrido M, Leers J, Heath H, Soochit W, Joosen L, Jonkers I, Demmers J, van der Reijden M, Torrano V, Grosveld F, Delgado MD, Renkawitz R, Galjart N, Sleutels F (2010) CTCF regulates the local epigenetic state of ribosomal DNA repeats. Epigenetics Chromatin 3:19PubMedCentralCrossRefPubMedGoogle Scholar
- Waddington CH (1957) The strategy of the genesGoogle Scholar
- Wang W, Wan T, Becher H, Kuderova A, Leitch IJ, Garcia S, Leitch AR, Kovařík A (2018) Remarkable variation of ribosomal DNA organization and copy number in gnetophytes, a distinct lineage of gymnosperms. Ann BotGoogle Scholar