Unmasking the Genome: The End of Junk DNA
- Authors
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D. Budinsky
Author
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M. Nailor
Author
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- Abstract
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For much of the late twentieth century, the roughly 98% of the human genome that does not code for protein was widely characterized as “junk,” a passive reservoir of evolutionary debris. This paper surveys the accumulating evidence that has eroded that characterization. Drawing on the ENCODE project’s report of pervasive biochemical activity across the genome, together with functional studies of pseudogenes, long noncoding RNAs, ALU elements, synonymous codon usage, heterochromatin, solo long terminal repeats, and endogenous retroviruses, it argues that a large and growing fraction of noncoding DNA participates in gene regulation, chromatin organization, development, immune defense, and tumor suppression. The paper also engages the principal objections raised in defense of the junk DNA paradigm, including the claims that biochemical activity does not entail function and that a lack of sequence conservation implies a lack of function, and it offers responses grounded in the metabolic cost of transcription, the scarcity of transcription factors, and the existence of species-specific and structurally defined functions. The genome is presented not as an accumulation of accidents but as a densely layered, information-rich system consistent with design.
- Author Biographies
- References
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1. ENCODE Project Consortium. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57–74. https://doi.org/10.1038/nature11247
2. Jandura, A., & Krause, H. M. (2017). The new RNA world: Growing evidence for long noncoding RNA functionality. Trends in Genetics, 33(10), 665–676. https://doi.org/10.1016/j.tig.2017.07.003
3. Zhao, Y., Granas, D., & Stormo, G. D. (2016). Inferring binding energies from selected binding sites. Genome Research, 26(6), 760–771. https://doi.org/10.1101/gr.200691.115
4. Poliseno, L., Salmena, L., Zhang, J., Carver, B., Haveman, W. J., & Pandolfi, P. P. (2010). A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature, 465(7301), 1033–1038. https://doi.org/10.1038/nature09144
5. Johnsson, P., Ackley, A., Vidarsdottir, L., Lui, W. O., Corcoran, M., Grandér, D., & Morris, K. V. (2013). A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. RNA Biology, 10(12), 1834–1842. https://doi.org/10.4161/rna.27216
6. Ransohoff, J. D., Wei, Y., & Khavari, P. A. (2018). The functions and unique features of long intergenic non-coding RNA. Nature Reviews Molecular Cell Biology, 19(3), 143–157. https://doi.org/10.1038/nrm.2017.104
7. Batzer, M. A., & Deininger, P. L. (2002). Alu repeats and human genomic diversity. Nature Reviews Genetics, 3(5), 370–379. https://doi.org/10.1038/nrg798 [Supplement: Cordaux, R., & Batzer, M. A. (2009). The impact of retrotransposons on human genome evolution. Nature Reviews Genetics, 10(10), 691–703. https://doi.org/10.1038/nrg2640]
8. Sauna, Z. E., & Kimchi-Sarfaty, C. (2011). Understanding the contribution of synonymous mutations to human disease. Nature Reviews Genetics, 12(10), 683–691. https://doi.org/10.1038/nrg3051
9. Saksouk, N., Simboeck, E., & Déjardin, J. (2015). Constitutive heterochromatin formation and transcription in mammals. Epigenetics & Chromatin, 8, 3. https://doi.org/10.1186/1756-8935-8-3
10. Rebollo, R., Romanish, M. T., & Mager, D. L. (2012). Transposable elements: an abundant and natural source of regulatory sequences for host genes. Annual Review of Genetics, 46, 21–42. https://doi.org/10.1146/annurev-genet-110711-155621
11. Imakawa, K., & Nakagawa, S. (2017). The role of endogenous retroviruses in the placenta. Placenta, 60, 161–167. https://doi.org/10.1016/j.placenta.2017.06.008
12. Chuong, E. B., Elde, N. C., & Feschotte, C. (2017). Regulatory activities of transposable elements: from conflicts to benefits. Nature Reviews Genetics, 18(2), 71–86. https://doi.org/10.1038/nrg.2016.139
13. Babaian, A., & Mager, D. L. (2016). Endogenous retroviral promoters in the human genome. Retrovirology, 13, 65. https://doi.org/10.1186/s12977-016-0301-1
14. Tarlinton, R. E., Meers, J., & Young, P. R. (2006). Retroviral invasion of the koala genome. Nature, 442(7098), 79–81. https://doi.org/10.1038/nature04841 [Supplement: Feschotte, C., & Gilbert, C. (2012). Endogenous viruses: insights into viral evolution and impact on host biology. Nature Reviews Genetics, 13(4), 283–296. https://doi.org/10.1038/nrg3199]
15. Ito, J., Sugimoto, R., Nakaoka, H., Yamada, S., Kimura, T., Hayano, T., ... Inoue, I. (2017). Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses. Genome Research, 27(11), 1963–1973. https://doi.org/10.1101/gr.219216.116
16. Dekker, J., Marti-Renom, M. A., & Mirny, L. A. (2013). Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nature Reviews Genetics, 14(6), 390–403. https://doi.org/10.1038/nrg3454 [Supplement: Kempfer, R., & Pombo, A. (2020). Methods for mapping 3D chromosome architecture. Nature Reviews Genetics, 21, 207–226. https://doi.org/10.1038/s41576-019-0195-2]
17. Jeffery, C. J. (2014). Protein moonlighting: what is it, and why is it important? Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1644), 20130589. https://doi.org/10.1098/rstb.2013.0589
18. Sverdlov, E. D. (2000). Retroviruses and primate evolution. BioEssays, 22(2), 161–171. https://doi.org/10.1002/(SICI)1521-1878(200002)22:2<161::AID-BIES7>3.0.CO;2-X
19. Tristem, M. (2000). Identification and characterization of novel human endogenous retrovirus families by phylogenetic screening of the Human Genome Mapping Project database. Journal of Virology, 74(8), 3715–3730. https://doi.org/10.1128/JVI.74.8.3715-3730.2000
20. Walkup, L. K. (2000). “Junk” DNA: Evolutionary discards or God’s tools? Journal of Creation, 14(2), 18–30. https://creation.com/junk-dna-evolutionary-discards-or-gods-tools
21. Wood, T. C. (2002). The AGEing process: Rapid post-Flood intrabaraminic diversification caused by altruistic genetic elements (AGEs). Origins, 54, 5–34.
22. Mao, L., Todd Wood, T. C., Yu, Y., Budiman, M. A., Tomkins, J., Woo, S.-S., Sasinowski, M., Presting, G., Frisch, D., Goff, S., Dean, R. A., & Wing, R. A. (2000). Rice transposable elements: A survey of 73,000 sequence-tagged-connectors. Genome Research, 10(7), 982–990. https://doi.org/10.1101/gr.10.7.982
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- 2026-07-18
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