The Myth of Junk DNA

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Joatn h a n W ells

S eattle Discovery Institute Press 2011 Description According to a number of leading proponents of Darwin’s theory, “junk DNA”—the non-protein coding portion of DNA—provides decisive evidence for Darwinian evolution and against intelligent design, since an intelligent designer would presumably not have filled our genome with so much garbage. But in this provocative book, biologist Jonathan Wells exposes the claim that most of the genome is little more than junk as an anti-scientific myth that ignores the evidence, impedes research, and is based more on theological speculation than good science. Copyright Notice Copyright © 2011 by Jonathan Wells. All Rights Reserved. Publisher’s Note This book is part of a series published by the Center for Science & Culture at Discovery Institute in Seattle. Previous books include The Deniable Darwin by David Berlinski, In the Beginning and Other Essays on Intelligent Design by Granville Sewell, God and Evolution: Protestants, Catholics, and Jews Explore Darwin’s Challenge to Faith, edited by Jay Richards, and Darwin’s Conservatives: The Misguided Questby John G. West. Library Cataloging Data The Myth of Junk DNA by Jonathan Wells (1942– ) Illustrations by Ray Braun 174 pages, 6 x 9 x 0.4 inches & 0.6 lb, 229 x 152 x 10 mm. & 0.26 kg Library of Congress Control Number: 2011925471 BISAC: SCI029000 SCIENCE / Life Sciences / Genetics & Genomics BISAC: SCI027000 SCIENCE / Life Sciences / Evolution ISBN-13: 978-1-9365990-0-4 (paperback) Publisher Information Discovery Institute Press, 208 Columbia Street, Seattle, WA 98104 Internet: http://www.discoveryinstitutepress.com/ Published in the United States of America on acid-free paper. First Edition, First Printing. May 2011. Praise for The Myth of Junk DNA

“Jonathan Wells has clearly done his homework. In The Myth of Junk DNA, he cites hundreds of research articles as he describes the expanding story of non-coding DNA—the supposed ‘junk DNA.’ It is quite possibly the most thorough review of the subject available. Dr. Wells makes it clear that our early understanding of DNA was incomplete, and genomics research is now revealing levels of control and complexity inside our cells that were undreamed of in the 1980s. Far from providing evidence for Dar- winism, the story of non-coding DNA rather serves to increase our appre- ciation for the design of life.” Ralph Seelke, Ph.D. Professor of Microbial Genetics and Cell Biology University of Wisconsin-Superior “Citing hundreds of peer-reviewed articles which show that more and more of the genome is functional, Jonathan Wells delivers a powerful and carefully researched broadside against the ‘junk DNA hypothesis.’ Even biologists who firmly reject the notion of intelligent design must surely acknowledge on the evidence presented in this timely book that appealing to ‘junk DNA’ to defend the Darwinian framework no longer makes any sense.” Michael Denton, Ph.D. Medical Geneticist and Author of Nature’s Destiny “This is an excellent and in-depth discussion of several key points of the subject of ‘junk-DNA.’ The author shows for many prime ex- amples still advanced by leading neo-Darwinians that the ‘Darwin-of-the- gaps’ approach doesn’t function or is at least doubtful.” Wolf-Ekkehard Lönnig, Ph.D. Senior Scientist, Department of Molecular Plant Genetics Max Planck Institute for Plant Breeding Research (retired) “There is a box in the biological sciences into which all evidence must be placed. That box is called Darwinian evolution. InThe Myth of Junk DNA Jonathan Wells tells the intriguing story of ‘junk’ DNA—the idea that non-protein coding DNA, which accounts for the majority of the DNA in the genome, is non-functional and without purpose; the result of the unguided purposeless process of random mutation and natural selection that produced it. In recent years, however, numerous researchers—not necessarily opponents of Darwinian evolution or advocates of intelligent design—have discovered many functions for non-protein coding DNA, which are thoroughly reviewed by Wells in this book. Unfortunately, in their effort to keep the ‘junk’ label attached to non-protein coding DNA so that it remains in the box of Darwinian evolution, a number of prominent Darwinists continue to insist, in spite of the recent results to the contrary, that it is largely left-over waste from the evolutionary process. As Wells clearly demonstrates in his book, this dogmatic commitment inhibits the scientific process. Science needs to be guided by objective evaluation of the evidence, and scientists should not allow their thinking to be arbitrarily re- stricted by dogmatic ideas. We need scientists who think outside the Dar- winian box. Wells’s book not only informs its readers of very recent research results, but also encourages them to think objectively and clearly about a key discovery in biology and to approach biological research with more cre- ativity. It is a great read.” Russell W. Carlson, Ph.D. Professor of Biochemistry and Molecular Biology University of Georgia “For years, Darwinists have claimed that most DNA is left-over detritus from failed evolutionary experiments. This ‘junk DNA’ has been offered as evidence for Darwinism and evidence against intelligent design. The only problem with the claim, as Jonathan Wells shows in this fascinat- ing book, is that it’s not true. Careful scientists have known for some time that the non-coding regions of DNA have all manner of function, so it is surprising to see prominent Darwinian scientists and their spokesmen continue to push the party line. Now that the evidence against the junk DNA story is indisputable, its defenders will want to beat a hasty retreat. The Myth of Junk DNA will make it hard for them to cover their tracks.” Jay Richards, Ph.D. Co-Author, The Privileged Planet, and Editor, God and Evolution Contents

Preface� �� 9

1. The Controversy Over Darwinian Evolution ��11

2. Junk DNA: The Last Icon of Evolution? �� 17

3. Most DNA Is Transcribed into RNA ��29

4. Introns and the Splicing Code ��39

5. Pseudogenes—Not So Pseudo after All ��47

6. Jumping Genes and Repetitive DNA ��57

7. Functions Independent of Exact Sequence ��71

8. Some Recent Defenders of Junk DNA ��81

9. Summary of the Case for Functionality in Junk DNA ��89

10. From Junk DNA to a New Understanding of the Genome 97

Appendix: The Vitamin C Pseudogene ��109

Notes �� 115

Glossary ��161

Index ��171 Notes 1. The Controversy Over 10. Jonathan Wells, “Deepening Darwin’s Darwinian Evolution Dilemma,” Discovery Institute (Septem- 1. Theodosius Dobzhansky,Genetics and the ber 16, 2009). Freely accessible (2011) at Origin of Species, Reprinted 1982. (New http://www.discovery.org/a/12471 York: Columbia University Press, 1937), 11. W. Ford Doolittle, “The practice of clas- p. 12. sification and the theory of evolution, and 2. Keith Stewart Thomson, “Natural Selec- what the demise of Charles Darwin’s tree tion and Evolution’s Smoking Gun,” Amer- of life hypothesis means for both of them,” ican Scientist 85 (1997): 516–518. Philosophical Transactions of the Royal Soci- 3. Alan Linton, “Scant Search for the Maker,” ety of London B 364 (2009): 2221–2228. The Times Higher Education Supplement 12. Carl R. Woese & Nigel Goldenfeld, (April 20, 2001), Book Section, p. 29. “How the Microbial World Saved Evolu- Freely accessible (2011) at http://www. tion from the Scylla of Molecular Biology timeshighereducation.co.uk/story.asp?st and the Charybdis of the Modern Syn- oryCode=159282§ioncode=31 thesis,” Microbiology and Molecular Biology 73 (2009): 14–21. Freely accessible 4. Jonathan Wells, The Politically Incorrect Reviews (2011) at http://mmbr.asm.org/cgi/re- Guide to Darwinism and Intelligent Design (Washington, DC: Regnery Publishing, print/73/1/14 2006), Chapter 5. More information avail- 13. Wells, The Politically Incorrect Guide to able online (2011) at http://www.discov- Darwinism and Intelligent Design, Chapter ery.org/a/3699 4. 5. Jonathan Wells, Icons of Evolution: Science 14. Gavin de Beer, Homology: An Unsolved or Myth? (Washington, DC: Regnery Pub- Problem (London: Oxford University Press, lishing, 2000). More information available 1971), pp. 15–16. online (2011) at http://www.iconsofevo- 15. Wells, Icons of Evolution: Science or Myth?, lution.com/ Chapter 4. 6. Charles Darwin, The Origin of Species by 16. Charles Darwin, “Letter to Asa Gray, Means of Natural Selection, First Edition September 10, 1860,” in Francis Darwin (London: John Murray, 1859), p. 130. (editor), The Life and Letters of Charles Freely accessible (2011) at http://darwin- Darwin (London: John Murray, 1887), Vol. online.org.uk/content/frameset?viewtyp II, p. 338. Freely accessible (2011) at http:// e=side&itemID=F373&pageseq=148 darwin-online.org.uk/content/frameset 7. Darwin, The Origin of Species, p. 282. ?viewtype=side&itemID=F1452.2&pa Freely accessible (2010) at http://darwin- geseq=354 online.org.uk/content/frameset?viewtyp 17. Rudolf A. Raff,The Shape of Life: Genes, e=side&itemID=F373&pageseq=300 Development, and the Evolution of Animal 8. James W. Valentine, Stanley M. Awramik, Form (Chicago: The University of Chicago Philip W. Signor and Peter M. Sadler, Press, 1996), pp. 195, 208–209. “The Biological Explosion at the Precam- 18. Jonathan Wells, “Haeckel’s Embryos & brian-Cambrian Boundary,” Evolutionary Evolution: Setting the Record Straight,” Biology 25 (1991): 279–356. The American Biology Teacher61 (May, 9. Jeffrey S. Levinton, “The Big Bang of 1999): 345–349. Freely accessible (2011) at Animal Evolution,” Scientific American 267 http://www.discovery.org/a/3071 (November, 1992): 84–91. 116 / Notes 2. Junk DNA – The Last Icon of Evolution?

19. Wells, Icons of Evolution: Science or Myth? mental Biology, Number XII (Cambridge: Chapter 5. Cambridge University Press, 1958), pp. 138–163. 2. Junk DNA – The Last 10. Judson, The Eighth Day of Creation, p. 217. Icon of Evolution? 11. Richard Dawkins, The Selfish Gene (New 1. Horace Freeland Judson, The Eighth Day of York: Oxford University Press, 1976), pp. Creation (New York: Simon and Schuster, 2, 24–25. 1979), p. 175. 12. Susumu Ohno, “So much ‘junk’ DNA 2. Francis Darwin (editor), The Life and in our genome,” Brookhaven Symposia in (London: John Letters of Charles Darwin Biology 23 (1972): 366–70. Freely acces- Murray, 1887), Volume I, p. 309. Freely sible (2011) at http://www.junkdna.com/ accessible (2011) at http://darwin-online. ohno.html org.uk/content/frameset?viewtype=side &itemID=F1452.1&pageseq=327 13. David E. Comings, “The Structure and Function of Chromatin,” Advances in Hu- 3. Francis Darwin & A.C. Seward (editors), man Genetics 3 (1972): 237–431. More Letters of Charles Darwin (London: John Murray, 1903), Volume 1, p. 321. 14. Dawkins, The Selfish Gene, p. 47. Freely accessible (2011) at http://darwin- 15. W. Ford Doolittle & Carmen Sapienza, online.org.uk/content/frameset?view “Selfish genes, the phenotype paradigm type=side&itemID=F1548.1&pages and genome evolution,” Nature 284 (1980): eq=370 601–603. 4. Francis Darwin (editor), The Life and 16. Leslie E. Orgel & Francis H. C. Crick, Letters of Charles Darwin (London: John “Selfish DNA: the ultimate parasite,”Na- Murray, 1887), Volume II, p. 312. Freely ture 284 (1980): 604–607. accessible (2011) at http://darwin-online. 17. Thomas Cavalier-Smith, “How selfish is org.uk/content/frameset?viewtype=side DNA?” Nature 285 (1980): 617–618. &itemID=F1452.2&pageseq=328 18. Gabriel Dover, “Ignorant DNA?” Nature 5. William Bateson, Mendel’s Principles of 285 (1980): 618–620. Heredity (New York: G. P. Putnam’s Sons, 19. Charles B. Thaxton, Walter L. Bradley & 1913), p. 329. Roger L. Olsen, The Mystery of Life’s Ori- 6. “Mendel, Mendelism,” The Catholic Ency- gin (Dallas, TX: Lewis and Stanley, 1984), clopedia. Freely accessible (2011) at http:// pp. 210–211. www.newadvent.org/cathen/10180b. 20. Michael Denton, Evolution: A Theory htm in Crisis (Bethesda, MD: Adler & Adler, 7. James D. Watson & Francis H. C. Crick, 1985), p. 341. “Molecular Structure of Nucleic Acids: A 21. Phillip E. Johnson, Darwin On Trial. Structure for Deoxyribose Nucleic Acid,” (Washington, DC: Regnery Gateway, Nature 171 (1953): 737–738. Freely acces- 1991), p. 144. sible (2011) at http://www.annals.org/ 22. Kenneth R. Miller, “Life’s Grand Design,” cgi/reprint/138/7/581.pdf Technology Review 97 (February–March 8. James D. Watson & Francis H. C. Crick, 1994): 24–32. Freely accessible (2011) at “Genetical Implications of the Structure http://www.millerandlevine.com/km/ of Deoxyribonucleic Acid,” Nature 171 evol/lgd/index.html (1953): 964–967. 23. Richard Dawkins, A Devil’s Chaplain: 9. Francis H. C. Crick, “On Protein Synthe- Reflections on Hope, Lies, Science, and Love sis,” The Biological Replication of Macromol- (New York: Mariner Books, 2004), p. 99. ecules, Symposia of the Society for Experi- 117 / Notes 3. Most DNA Is Transcribed into RNA

24. Douglas J. Futuyma, Evolution (Sunder- 3. Nobel Prize for Physiology or Medicine land, MA: Sinauer Associates, 2005), pp. (1993) awarded to Richard J. Roberts 48–49, 456, 530. and Phillip A. Sharp for their “discovery 25. Michael Shermer, Why Darwin Matters: of split genes.” Press release available The Case Against Intelligent Design (New online (2011) at http://nobelprize.org/ York: Holt, 2006), pp. 74–75. nobel_prizes/medicine/laureates/1993/ press.html 26. Francis S. Collins, The Language of God: A Scientist Presents Evidence for Belief (New 4. David M. Glover & David S. Hogness, “A York: Free Press, 2006), pp. 136–137. Novel Arrangement of the 18s and 28s Sequences in a Repeating Unit of 27. Philip Kitcher, Living With Darwin: Evo- Drosoph- rDNA,” 10 (1977): lution, Design, and the Future of Faith (New ila melanogaster Cell York: Oxford, 2007), pp. 57–58, 111. 167–176. 5. Walter Gilbert, “Why genes in pieces?” 28. Kenneth R. Miller, Only a Theory: Evolu- 271 (1978): 501. tion and the Battle for America’s Soul (New Nature York: Viking, 2008), pp. 97–98. 6. P. M. B. Walker & Anne McLaren, “Frac- tionation of mouse deoxyribonucleic acid 29. Jerry A. Coyne, Why Evolution Is True (New York: Viking, 2009), pp. 66–67, 81. on hydroxyapatite,” Nature 208 (1965): 1175–1179. 30. Richard Dawkins, The Greatest Show on 7. Roy J. Britten & D. E. Kohne, “Repeated Earth: The Evidence for Evolution (New York: Free Press, 2009), pp. 332–333. Sequences in DNA,” Science 161 (1968): 529–540. 31. John C. Avise, Inside the Human Genome: 8. Reviewed in W. G. Flamm, “Highly A Case for Non-Intelligent Design (Oxford: Oxford University Press, 2010), pp. 82, Repetitive Sequences of DNA in Chromo- 115. somes,” International Review of Cytology 32 (1972): 1–51. 32. John C. Avise, “Footprints of nonsentient 9. Bruce Alberts, Alexander Johnson, Julian design inside the human genome,” Proceed- Lewis, Martin Raff, Keith Roberts & ings of the National Academy of Sciences Peter Walter, , USA 107 Supplement 2 (2010): 8969– Molecular Biology of the Cell 8976. Freely accessible (2011) at http:// Fourth Edition (New York: Garland Sci- www.pnas.org/content/107/suppl.2/8969. ence, 2002), p. 203. full.pdf+html 10. Joshua Lederberg & Alexa T. McCray, “ ‘Ome Sweet ‘Omics—A Genealogi- 3. Most DNA Is cal Treasury of Words,” The Scientist 15 Transcribed into RNA (2001): 8. Freely accessible (2011) at http:// 1. Francis H. C. Crick, “On Protein Synthe- www.lhncbc.nlm.nih.gov/lhc/docs/pub- sis,” The Biological Replication of Macromol- lished/2001/pub2001047.pdf ecules, Symposia of the Society for Experi- 11. Edmund Pillsbury, “A History of Ge- mental Biology, Number XII (Cambridge: nome Sequencing,” Computational Biol- Cambridge University Press, 1958), pp. ogy and Bioinformatics, Yale University 138–163. (1997). Freely accessible (2011) at http:// 2. C. Mulder, J. R. Arrand, H. Delius, W. bioinfo.mbb.yale.edu/course/projects/ Keller, U. Pettersson, R. J. Roberts & P. final-4/ A. Sharp, “Cleavage Maps of DNA from 12. National Center for Biotechnology Infor- Adenovirus Types 2 and 5 by Restriction mation (GenBank). http://www.ncbi.nlm. Endonucleases EcoRI and HpaI,” Cold nih.gov/genbank/ Spring Harbor Symposia on Quantitative Biology 39 (1975): 397–400. 118 / Notes 3. Most DNA Is Transcribed into RNA

13. EMBL Nucleotide Sequence Database. M. Kedzierski, B. L. King, A. Konagaya, http://www.ebi.ac.uk/embl/ I. V. Kurochkin, Y. Lee, B. Lenhard, P. 14. DNA Data Bank of Japan. http://www. A. Lyons, D. R. Maglott, L. Maltais, L. ddbj.nig.ac.jp/ Marchionni, L. McKenzie, H. Miki, T. 15. “International Consortium Completes Nagashima, K. Numata, T. Okido, W. J. Human Genome Project,” National Pavan, G. Pertea, G. Pesole, N. Petrovsky, Human Genome Research Institute, R. Pillai, J. U. Pontius, D. Qi, S. Ram- Bethesda, MD (April 14, 2003). Freely achandran, T. Ravasi, J. C. Reed, D. J. accessible (2011) at http://www.genome. Reed, J. Reid, B. Z. Ring, M. Ringwald, A. gov/11006929 Sandelin, C. Schneider, C. A. M. Semple, M. Setou, K. Shimada, R. Sultana, Y. 16. “The ENCODE Project,” National Hu- Takenaka, M. S. Taylor, R. D. Teasdale, man Genome Research Institute, Bethesda, M. Tomita, R. Verardo, L. Wagner, C. MD (December 28, 2009). Freely ac- Wahlestedt, Y. Wang, Y. Watanabe, C. cessible (2011) at http://www.genome. Wells, L. G. Wilming, A. Wynshaw-Boris, gov/10005107 M. Yanagisawa, I. Yang, L. Yang, Z. Yuan, 17. “History,” RIKEN Omic Sciences Center, M. Zavolan, Y. Zhu, A. Zimmer, P. Carn- Yokohama, Japan (2009). Freely accessible inci, N. Hayatsu, T. Hirozane-Kishikawa, (2011) at http://www.osc.riken.jp/eng- H. Konno, M. Nakamura, N. Sakazume, lish/outline/history/ K. Sato, T. Shiraki, K. Waki, J. Kawai, K. 18. FANTOM Consortium, Yokohama, Aizawa, T. Arakawa, S. Fukuda, A. Hara, Japan. http://fantom.gsc.riken.jp/4/ W. Hashizume, K. Imotani, Y. Ishii, M. 19. Fred A. Wright, William J. Lemon, Wei Itoh, I. Kagawa, A. Miyazaki, K. Sakai, D. Zhao, Russell Sears, Degen Zhuo, Jian- D. Sasaki, K. Shibata, A. Shinagawa, A. Ping Wang, Hee-Yung Yang, Troy Baer, Yasunishi, M. Yoshino, R. Waterston, Don Stredney, Joe Spitzner, Al Stutz, Ralf E. S. Lander, J. Rogers, E. Birney & Y. Krahe & Bo Yuan, “A draft annotation Hayashizaki, “Analysis of the mouse tran- and overview of the human genome,” Ge- scriptome based on functional annotation nome Biology 2:7 (2001). Freely accessible of 60,770 full-length cDNAs,” Nature 420 (2011) at http://genomebiology.com/ (2002): 563–573. content/pdf/gb-2001-2-7-research0025. 21. Philipp Kapranov, Simon E. Cawley, pdf Jorg Drenkow, Stefan Bekiranov, Robert 20. Y. Okazaki, M. Furuno, T. Kasukawa, J. L. Strausberg, Stephen P. A. Fodor & Adachi, H. Bono, S. Kondo, I. Nikaido, N. Thomas R. Gingeras, “Large-Scale Tran- Osato, R. Saito, H. Suzuki, I. Yamanaka, scriptional Activity in Chromosomes 21 H. Kiyosawa, K. Yagi, Y. Tomaru, Y. and 22,” Science 296 (2002): 916–919. Hasegawa, A. Nogami, C. Schönbach, 22. P. Carninci, T. Kasukawa, S. Katayama, T. Gojobori, R. Baldarelli, D. P. Hill, C. J. Gough, M. C. Frith, N. Maeda, R. Bult, D. A. Hume, J. Quackenbush, L. Oyama, T. Ravasi, B. Lenhard, C. Wells, M. Schriml, A. Kanapin, H. Matsuda, S. R. Kodzius, K. Shimokawa, V. B. Bajic, S. Batalov, K. W. Beisel, J. A. Blake, D. Bradt, E. Brenner, S. Batalov, A. R. R. Forrest, V. Brusic, C. Chothia, L. E. Corbani, S. M. Zavolan, M. J. Davis, L. G. Wilm- Cousins, E. Dalla, T. A. Dragani, C. F. ing, V. Aidinis, J. E. Allen, A. Ambesi- Fletcher, A. Forrest, K. S. Frazer, T. Gaas- Impiombato, R. Apweiler, R. N. Aturaliya, terland, M. Gariboldi, C. Gissi, A. Godzik, T. L. Bailey, M. Bansal, L. Baxter, K. W. J. Gough, S. Grimmond, S. Gustincich, Beisel, T. Bersano, H. Bono, A. M. Chalk, N. Hirokawa, I. J. Jackson, E. D. Jarvis, K. P. Chiu, V. Choudhary, A. Christof- A. Kanai, H. Kawaji, Y. Kawasawa, R. fels, D. R. Clutterbuck, M. L. Crowe, E. 119 / Notes 3. Most DNA Is Transcribed into RNA

Dalla, B. P. Dalrymple, B. de Bono, G. & Y. Hayashizaki, “The Transcriptional Della Gatta, D. di Bernardo, T. Down, P. Landscape of the Mammalian Genome,” Engstrom, M. Fagiolini, G. Faulkner, C. Science 309 (2005): 1559–1563. Available F. Fletcher, T. Fukushima, M. Furuno, online with registration (2011) at http:// S. Futaki, M. Gariboldi, P. Georgii- www.sciencemag.org/cgi/content/ Hemming, T. R. Gingeras, T. Gojobori, full/309/5740/1559 R. E. Green, S. Gustincich, M. Harbers, 23. Michael Pheasant & John S. Mat- Y. Hayashi, T. K. Hensch, N. Hirokawa, tick, “Raising the estimate of functional D. Hill, L. Huminiecki, M. Iacono, K. human sequences,” Genome Research 17 Ikeo, A. Iwama, T. Ishikawa, M. Jakt, A. (2007): 1245–1253. Freely accessible Kanapin, M. Katoh, Y. Kawasawa, J. Kelso, (2011) at http://genome.cshlp.org/con- H. Kitamura, H. Kitano, G. Kollias, S. tent/17/9/1245.full.pdf+html P. T. Krishnan, A. Kruger, S. K. Kum- 24. Ewan Birney, John A. Stamatoyan- merfeld, I. V. Kurochkin, L. F. Lareau, D. nopoulos, Anindya Dutta, Roderic Guigó, Lazarevic, L. Lipovich, J. Liu, S. Liuni, S. Thomas R. Gingeras, Elliott H. Margulies, McWilliam, M. Madan Babu, M. Madera, Zhiping Weng, Michael Snyder, Em- L. Marchionni, H. Matsuda, S. Matsu- manouil T. Dermitzakis, Robert E. Thur- zawa, H. Miki, F. Mignone, S. Miyake, K. man, Michael S. Kuehn, Christopher M. Morris, S. Mottagui-Tabar, N. Mulder, Taylor, Shane Neph, Christoph M. Koch, N. Nakano, H. Nakauchi, P. Ng, R. Nils- Saurabh Asthana, Ankit Malhotra, Ivan son, S. Nishiguchi, S. Nishikawa, F. Nori, Adzhubei, Jason A. Greenbaum, Robert O. Ohara, Y. Okazaki, V. Orlando, K. C. M. Andrews, Paul Flicek, Patrick J. Boyle, Pang, W. J. Pavan, G. Pavesi, G. Pesole, N. Hua Cao, Nigel P. Carter, Gayle K. Clel- Petrovsky, S. Piazza, J. Reed, J. F. Reid, B. land, Sean Davis, Nathan Day, Pawandeep Z. Ring, M. Ringwald, B. Rost, Y. Ruan, S. Dhami, Shane C. Dillon, Michael O. L. Salzberg, A. Sandelin, C. Schneider, C. Dorschner, Heike Fiegler, Paul G. Giresi, Schönbach, K. Sekiguchi, C. A. M. Sem- Jeff Goldy, Michael Hawrylycz, Andrew ple, S. Seno, L. Sessa, Y. Sheng, Y. Shibata, Haydock, Richard Humbert, Keith H. Shimada, K. Shimada, D. Silva, B. D. James, Brett E. Johnson, Ericka M. Sinclair, S. Sperling, E. Stupka, K. Sugi- Johnson, Tristan T. Frum, Elizabeth R. ura, R. Sultana, Y. Takenaka, K. Taki, K. Rosenzweig, Neerja Karnani, Kirsten Lee, Tammoja, S. L. Tan, S. Tang, M. S. Taylor, Gregory C. Lefebvre, Patrick A. Navas, J. Tegner, S. A. Teichmann, H. R. Ueda, Fidencio Neri, Stephen C. J. Parker, Peter E. van Nimwegen, R. Verardo, C. L. Wei, J. Sabo, Richard Sandstrom, Anthony K. Yagi, H. Yamanishi, E. Zabarovsky, S. Shafer, David Vetrie, Molly Weaver, Sarah Zhu, A. Zimmer, W. Hide, C. Bult, S. M. Wilcox, Man Yu, Francis S. Collins, Job Grimmond, R. D. Teasdale, E. T. Liu, V. Dekker, Jason D. Lieb, Thomas D. Tullius, Brusic, J. Quackenbush, C. Wahlestedt, J. Gregory E. Crawford, Shamil Sunayev, S. Mattick, D. A. Hume, C. Kai, D. Sasaki, William S. Noble, Ian Dunham, France Y. Tomaru, S. Fukuda, M. Kanamori-Ka- Denoeud, Alexandre Reymond, Philipp tayama, M. Suzuki, J. Aoki, T. Arakawa, Kapranov, Joel Rozowsky, Deyou Zheng, J. Iida, K. Imamura, M. Itoh, T. Kato, H. Robert Castelo, Adam Frankish, Jennifer Kawaji, N. Kawagashira, T. Kawashima, Harrow, Srinka Ghosh, Albin Sandelin, M. Kojima, S. Kondo, H. Konno, K. Na- Ivo L. Hofacker, Robert Baertsch, Damian kano, N. Ninomiya, T. Nishio, M. Okada, Keefe, Sujit Dike, Jill Cheng, Heather A. C. Plessy, K. Shibata, T. Shiraki, S. Su- Hirsch, Edward A. Sekinger, Julien La- zuki, M. Tagami, K. Waki, A. Watahiki, garde, Josep F. Abril, Atif Shahab, Chris- Y. Okamura-Oho, H. Suzuki, J. Kawai toph Flamm, Claudia Fried, Jörg Hack- 120 / Notes 3. Most DNA Is Transcribed into RNA

ermüller, Jana Hertel, Manja Lindemeyer, Morgan Park, Pamela J. Thomas, Alice Kristin Missal, Andrea Tanzer, Stefan C. Young, Robert W. Blakesley, Donna Washietl, Jan Korbel, Olof Emanuelsson, M. Muzny, Erica Sodergren, David A. Jakob S. Pedersen, Nancy Holroyd, Ruth Wheeler, Kim C. Worley, Huaiyang Taylor, David Swarbreck, Nicholas Mat- Jiang, George M. Weinstock, Richard A. thews, Mark C. Dickson, Daryl J. Thomas, Gibbs, Tina Graves, Robert Fulton, Elaine Matthew T. Weirauch, James Gilbert, Jorg R. Mardis, Richard K. Wilson, Michele Drenkow, Ian Bell, XiaoDong Zhao, K. Clamp, James Cuff, Sante Gnerre, David G. Srinivasan, Wing-Kin Sung, Hong B. Jaffe, Jean L. Chang, Kerstin Lindblad- Sain Ooi, Kuo Ping Chiu, Sylvain Foissac, Toh, Eric S. Lander, Maxim Koriabine, Tyler Alioto, Michael Brent, Lior Pachter, Mikhail Nefedov, Kazutoyo Osoegawa, Michael L. Tress, Alfonso Valencia, Siew Yuko Yoshinaga, Baoli Zhu, Pieter J. de Woh Choo, Chiou Yu Choo, Catherine Jong, Nathan D. Trinklein, Zhengdong Ucla, Caroline Manzano, Carine Wyss, D. Zhang, Leah Barrera, Rhona Stuart, Evelyn Cheung, Taane G. Clark, James David C. King, Adam Ameur, Stefan B. Brown, Madhavan Ganesh, Sandeep Enroth, Mark C. Bieda, Chia-Lin Wei, Patel, Hari Tammana, Jacqueline Chrast, Jonghwan Kim, Akshay A. Bhinge, Paul G. Charlotte N. Henrichsen, Chikatoshi Giresi, Nan Jiang, Jun Liu, Fei Yao, Wing- Kai, Jun Kawai, Ugrappa Nagalakshmi, Kin Sung, Kuo Ping Chiu, Vinsensius B. Jiaqian Wu, Zheng Lian, Jin Lian, Peter Vega, Charlie W.H. Lee, Patrick Ng, Atif Newburger, Xueqing Zhang, Peter Bickel, Shahab, Edward A. Sekinger, Annie Yang, John S. Mattick, Piero Carninci,Yoshihide Zarmik Moqtaderi, Zhou Zhu, Xiaoqin Hayashizaki, Sherman Weissman, Tim Xu, Sharon Squazzo, Matthew J. Oberley, Hubbard, Richard M. Myers, Jane Rogers, David Inman, Michael A. Singer, Todd A. Peter F. Stadler, Todd M. Lowe, Chia-Lin Richmond, Kyle J. Munn, Alvaro Rada- Wei, Yijun Ruan, Kevin Struhl, Mark Iglesias, Ola Wallerman, Jan Komorowski, Gerstein, Stylianos E. Antonarakis, Yutao Gayle K. Clelland, Robert M. Andrews, Fu, Eric D. Green, Ulaf Karaöz, William Joanna C. Fowler, Phillippe Couttet, Keith S. Noble, Alexandre Reymond, Adam D. James, Gregory C. Lefebvre, Alexander Siepel, James Taylor, Thomas D. Tullius, W. Bruce, Oliver M. Dovey, Peter D. Ellis, Laura A. Liefer, Kris A. Wetterstrand, Pawandeep Dhami, Cordelia F. Langford, Peter J. Good, Elise A. Feingold, Mark Nigel P. Carter, David Vetrie, David A. S. Guyer, Gregory M. Cooper, George Nix, Ian Bell, Ghia Euskirchen, Stephen Asimenos, Daryl J. Thomas, Colin N. Hartman, Jiaqian Wu, Alexander E. Ur- Dewey, Minmei Hou, Sergey Nikolaev, ban, Peter Kraus, Sara Van Calcar, Nate Juan I. Montoya-Burgos, Ari Löytynoja, Heintzman, Tae Hoon Kim, Kun Wang, Simon Whelan, Fabio Pardi, Tim Mass- Chunxu Qu, Gary Hon, Rosa Luna, ingham, Haiyan Huang, Nancy R. Zhang, Christopher K. Glass, M. Geoff Rosen- Ian Holmes, James C. Mullikin, Abel feld, Shelley Force Aldred, Sara J. Cooper, Ureta-Vidal, Benedict Paten, Michael Anason Halees, Jane M. Lin, Hennady P. Seringhaus, Deanna Church, Kate Rosen- Shulha, Xiaoling Zhang, Mousheng Xu, bloom, W. James Kent, Serafim Batzo- Jaafar N. S. Haidar, Yong Yu, Sherman glou, Nick Goldman, Ross C. Hardison, Weissman, Yijun Ruan, Jason D. Lieb, David Haussler, Webb Miller, Lior Vishwanath R. Iyer, Roland D. Green, Pachter, Arend Sidow, Gerard G. Bouf- Claes Wadelius, Ian Dunham, Peggy fard, Xiaobin Guan, Nancy F. Hansen, J. Farnham, Bing Ren, Rachel A. Harte, Jacquelyn R. Idol, Valerie V.B. Maduro, Angie S. Hinrichs, Heather Trumbower, Baishali Maskeri, Jennifer C. McDowell, Hiram Clawson, Jennifer Hillman-Jack- 121 / Notes 3. Most DNA Is Transcribed into RNA

son, Ann S. Zweig, Kayla Smith, Archana Chikatoshi Kai, Jun Kawai, Piero Carn- Thakkapallayil, Galt Barber, Robert M. inci, Yoshihide Hayashizaki, Christine Kuhn, Donna Karolchik, W. James Kent, Wells, Vladimir B. Bajic, Valerio Orlando, Lluis Armengol, Christine P. Bird, Taane James F. Reid, Boris Lenhard & Leonard G. Clark, Paul I. W. de Bakker, Andrew D. Lipovich, “Complex Loci in Human and Kern, Nuria Lopez-Bigas, Joel D. Martin, Mouse Genomes,” PLoS Genetics 2:4 Barbara E. Stranger, Abigail Woodroffe, (2006): e47. Freely accessible (2011) at Serafim Batzoglou, Eugene Davydov, An- http://www.plosgenetics.org/article/ tigone Dimas, Eduardo Eyras, Ingileif B. info%3Adoi%2F10.1371%2Fjournal. Hallgrímsdóttir, Julian Huppert, Heather pgen.0020047 Trumbower, Michael C. Zody, James C. 28. Yiping He, Bert Vogelstein, Victor Mullikin, Gonçalo R. Abecasis & Xavier E. Velculescu, Nickolas Papadopoulos Estivill, “Identification and analysis of & Kenneth W. Kinzler, “The Antisense functional elements in 1% of the human Transcriptomes of Human Cells,” Science genome by the ENCODE pilot project,” 322 (2008): 1855–1857. Nature 447 (2007): 799–816. Freely acces- 29. Kevin V. Morris, Sharon Santoso, sible (2011) at http://www.ncbi.nlm.nih. Anne-Marie Turner, Chiara Pastori, gov/pmc/articles/PMC2212820/pdf/ Peter G. Hawkins, “Bidirectional nihms27513.pdf Transcription Directs Both Transcrip- 25. Naoki Osato, Hitomi Yamada, Kouji tional Gene Activation and Suppression Satoh, Hisako Ooka, Makoto Yamamoto, in Human Cells,” PLoS Genetics 4:11 Kohji Suzuki, Jun Kawai, Piero Carninci, (2008): e1000258. Freely accessible Yasuhiro Ohtomo, Kazuo Murakami, (2011) at http://www.plosgenetics.org/ Kenichi Matsubara, Shoshi Kikuchi article/info:doi%2F10.1371%2Fjournal. & Yoshihide Hayashizaki, “Antisense pgen.1000258 transcripts with rice full-length cDNAs,” 30. Stefano Gustincich, Albin Sandelin, Genome Biology 5:1 (2003): R5. Freely Charles Plessy, Shintaro Katayama, Ro- accessible (2011) at http://genomebiology. berto Simone, Dejan Lazarevic, Yoshihide com/content/pdf/gb-2003-5-1-r5.pdf Hayashizaki & Piero Carninci, “The 26. S. Katayama, Y. Tomaru, T. Kasukawa, complexity of the mammalian transcrip- K. Waki, M. Nakanishi, M. Nakamura, tome,” Journal of Physiology 575:2 (2006): H. Nishida, C. C. Yap, M. Suzuki, J. 321–332. Freely accessible (2011) at http:// Kawai, H. Suzuki, P. Carninci, Y. Hayas- jp.physoc.org/content/575/2/321.full. hizaki, C. Wells, M. Frith, T. Ravasi, pdf+html K. C. Pang, J. Hallinan, J. Mattick, D. 31. Philipp Kapranov, Aarron T. Willing- A. Hume, L. Lipovich, S. Batalov, P. G. ham & Thomas R. Gingeras, “Genome- Engström, Y. Mizuno, M. A. Faghihi, A. wide transcription and the implications Sandelin, A. M. Chalk, S. Mottagui-Tabar, for genomic organization,” Nature Reviews Z. Liang, B. Lenhard & C. Wahlestedt, Genetics 8 (2007): 413–423. “Antisense Transcription in the Mamma- 32. Piero Carninci, “Constructing the lian Transcriptome,” Science 309 (2005): landscape of the mammalian transcrip- 1564–1566. tome,” Journal of Experimental Biology 27. Pär G. Engström, Harukazu Suzuki, 210 (2007): 1497–1506. Freely accessible Noriko Ninomiya, Altuna Akalin, Luca (2011) at http://jeb.biologists.org/cgi/ Sessa, Giovanni Lavorgna, Alessandro reprint/210/9/1497 Brozzi, Lucilla Luzi, Sin Lam Tan, Liang 33. Jia Qian Wu, Jiang Du, Joel Rozowsky, Yang, Galih Kunarso, Edwin Lian-Chong Zhengdong Zhang, Alexander E. Urban, Ng, Serge Batalov, Claes Wahlestedt, 122 / Notes 3. Most DNA Is Transcribed into RNA

Ghia Euskirchen, ShermanWeissman, cshlp.org/content/15/8/1034.full. Mark Gerstein & Michael Snyder, “Sys- pdf+html tematic analysis of transcribed loci in 38. Gil Bejerano, “Ultraconservation and ENCODE regions using RACE sequenc- the Human Genome Regulatory Land- ing reveals extensive transcription in the scape,” Lecture at Stanford University human genome,” Genome Biology 9:1 (April 15, 2009). Freely accessible (2011) at (2008): R3. Freely accessible (2011) at http://video.google.com/videoplay?doc http://genomebiology.com/content/pdf/ id=8213646681956800413# gb-2008-9-1-r3.pdf 39. John A. Bernat, Gregory E. Crawford, 34. Gill Bejerano, Michael Pheasant, Igor Aleksey Y. Ogurtsov, Francis S. Collins, Makunin, Stuart Stephen, W. James David Ginsburg & Alexey S. Kondrashov, Kent, John S. Mattick & David Haussler, “Distant conserved sequences flanking en- “Ultraconserved Elements in the Human dothelial-specific promoters contain tissue- Genome,” Science 304 (2004): 1321–1325. specific DNase-hypersensitive sites and 35. Albin Sandelin, Peter Bailey, Sara Bruce, over-represented motifs,” Human Molecu- Pär G. Engström, Joanna M Klos, Wyeth lar Genetics 15 (2006): 2098–2105. Freely W. Wasserman, Johan Ericson & Boris accessible (2011) at http://hmg.oxford- Lenhard, “Arrays of ultraconserved non- journals.org/cgi/reprint/15/13/2098 coding regions span the loci of key develop- 40. Tanya Vavouri, Klaudia Walter, Walter mental genes in vertebrate genomes,” BMC R Gilks, Ben Lehner and Greg Elgar, “Par- Genomics 5 (2004): 99. Freely accessible allel evolution of conserved non-coding (2011) at http://www.biomedcentral. elements that target a common set of devel- com/1471–2164/5/99 opmental regulatory genes from worms to 36. Adam Woolfe, Martin Goodson, Debbie humans,” Genome Biology 8:2 (2007): R15. K. Goode, Phil Snell, Gayle K. McEwen, Freely accessible (2011) at http://genome- Tanya Vavouri, Sarah F. Smith, Phil biology.com/2007/8/2/R15 North, Heather Callaway, Krys Kelly, 41. Jasmina Ponjavic, Chris P. Ponting & Klaudia Walter, Irina Abnizova, Walter Gerton Lunter, “Functionality or tran- Gilks, Yvonne J. K. Edwards, Julie E. scriptional noise? Evidence for selection Cooke & Greg Elgar, “Highly Conserved within long noncoding RNAs,” Genome Non-coding Sequences Are Associated Research 17 (2007): 556–565. Freely acces- with Vertebrate Development,” PLoS Biol- sible (2011) at http://genome.cshlp.org/ ogy 3:1 (2005): e7. Freely accessible (2011) content/17/5/556.full.pdf+html at http://www.plosbiology.org/article/ 42. Mitchell Guttman, Ido Amit, Manuel info%3Adoi%2F10.1371%2Fjournal. Garber, Courtney French, Michael F. pbio.0030007 Lin, David Feldser, Maite Huarte, Or 37. Adam Siepel, Gill Bejerano, Jakob S. Zuk, Bryce W. Carey, John P. Cassady, Pedersen, Angie S. Hinrichs, Minmei Moran N. Cabili, Rudolf Jaenisch, Tarjei Hou, Kate Rosenbloom, Hiram Clawson, S. Mikkelsen, Tyler Jacks, Nir Hacohen, John Spieth, LaDeana W. Hillier, Stephen Bradley E. Bernstein, Manolis Kellis, Aviv Richards, George M. Weinstock, Richard Regev, John L. Rinn & Eric S. Lander, K. Wilson, Richard A. Gibbs, W. James “Chromatin signature reveals over a thou- Kent, Webb Miller & David Haussler, sand highly conserved large non-coding “Evolutionarily conserved elements in ver- RNAs in mammals,” Nature 458 (2009): tebrate, insect, worm, and yeast genomes,” 223–227. Freely accessible (2011) at http:// Genome Research 15 (2005): 1034–1050. www.ncbi.nlm.nih.gov/pmc/articles/ Freely accessible (2011) at http://genome. PMC2754849/?tool=pubmed 123 / Notes 3. Most DNA Is Transcribed into RNA

43. Maciej Szymanski, Miroslawa Z. Bar- noncoding RNAs in the mouse brain,” ciszewska, Marek Zywicki & Jan Bar- Proceedings of the National Academy of Sci- ciszewski, “Noncoding RNA transcripts,” ences USA 105 (2008): 716–721. Freely Journal of Applied Genetics 44 (2003): accessible (2011) at http://www.pnas.org/ 1–19. Freely accessible (2011) at http:// content/105/2/716.full.pdf+html jag.igr.poznan.pl/2003-Volume-44/1/ 51. Johannes H. Urban & Jörg Vogel, “Two pdf/2003_Volume_44_1-1-19.pdf Seemingly Homologous Noncoding 44. John S. Mattick & Igor V. Makunin, RNAs Act Hierarchically to Activate “Non-coding RNA,” Human Molecular glmS mRNA Translation,” PLoS Biology Genetics 15 (2006): R17-R29. Freely acces- 6:3 (2008): e64. Freely accessible (2011) sible (2011) at http://hmg.oxfordjournals. at http://www.plosbiology.org/article/ org/cgi/reprint/15/suppl_1/R17 info%3Adoi%2F10.1371%2Fjournal. 45. Luis M. Mendes Soares & Juan Valcár- pbio.0060064 cel, “The expanding transcriptome: the 52. Piero Carninci, Jun Yasuda & Yoshihide genome as the ‘Book of Sand,’” EMBO Hayashizaki, “Multifaceted mammalian Journal 25 (2006): 923–931. Available transcriptome,” Current Opinion in Cell online with registration (2011) at http:// Biology 20 (2008): 274–280. www.nature.com/emboj/journal/v25/n5/ 53. Archa H. Fox, Yun Wah Lam, An- full/7601023a.html thony K. L. Leung, Carol E. Lyon, Jens 46. John L. Rinn, Michael Kertesz, Jordon K. Andersen, Matthias Mann & Angus I. Wang, Sharon L. Squazzo, Xiao Xu, Sa- Lamond, “Paraspeckles: a novel nuclear mantha A. Brugmann, Henry Goodnough, domain,” Current Biology 12 (2002): 13–25. Jill A. Helms, Peggy J. Farnham, Eran Freely accessible (2011) at http://www. Segal & Howard Y. Chang, “Functional cell.com/current-biology/retrieve/pii/ Demarcation of Active and Silent Chro- S0960982201006327 matin Domains in Human HOX Loci 54. Charles S. Bond & Archa H. Fox, “Para- by Non-Coding RNAs,” Cell 129 (2007): speckles: nuclear bodies built on long 1311–1323. Freely accessible (2011) at noncoding RNA,” Journal of Cell Biology http://www.ncbi.nlm.nih.gov/pmc/ar- 186 (2009): 637–644. Freely accessible ticles/PMC2084369/?tool=pubmed (2011) at http://jcb.rupress.org/con- 47. Gennadi V. Glinsky, “Phenotype-defin- tent/186/5/637.full.pdf+html ing functions of multiple non-coding RNA 55. Archa H. Fox & Angus I. Lamond, pathways,” Cell Cycle 7 (2008): 1630–1639. “Paraspeckles,” Cold Spring Harbor Perspec- Freely accessible (2011) at http://www. tives in Biology 2 (2010): a000687. Freely landesbioscience.com/journals/cc/ar- accessible (2011) at http://cshperspec- ticle/5976/ tives.cshlp.org/content/2/7/a000687. 48. Eugene V. Makeyev & Tom Maniatis, full.pdf+html “Multilevel Regulation of Gene Expres- 56. Christine M. Clemson, John N. sion by MicroRNAs,” Science 319 (2008): Hutchinson, Sergio A. Sara, Alexander 1789–1790 W. Ensminger, Archa H. Fox, Andrew 49. Paulo P. Amaral, Marcel E. Dinger, Tim Chess & Jeanne B. Lawrence, “An ar- R. Mercer & John S. Mattick, “The Eu- chitectural role for a nuclear noncoding karyotic Genome as an RNA Machine,” RNA: NEAT1 RNA is essential for the Science 319 (2008): 1787–1789. structure of paraspeckles,” Molecular Cell 50. Tim R. Mercer, Marcel E. Dinger, Su- 33 (2009): 717–726. Freely accessible san M. Sunkin, Mark F. Mehler & John (2011) at http://www.ncbi.nlm.nih.gov/ S. Mattick, “Specific expression of long 124 / Notes 4. Introns and the Splicing Code

pmc/articles/PMC2696186/pdf/ni- 4. Introns and the Splicing Code hms106615.pdf 1. Stuart E. Leff, Michael G. Rosenfeld & 57. Yasnory T. F. Sasaki, Takashi Ideue, Ronald M. Evans, “Complex transcrip- Miho Sano, Toutai Mituyama & Tetsuro tional units: diversity in gene expression by Hirose, “MENe/b noncoding RNAs alternative RNA processing,” Annual Re- are essential for structural integrity of view of Biochemistry 55 (1986): 1091–1117. nuclear paraspeckles,” Proceedings of the 2. Richard A. Padgett, Paula J. Grabowski, National Academy of Sciences USA 106 Maria M. Konarska, Sharon Seiler & Phil- (2009): 2525–2530. Freely accessible lip A. Sharp, “Splicing of messenger RNA (2011) at http://www.pnas.org/con- precursors,” Annual Review of Biochemistry tent/106/8/2525.full.pdf+html 55 (1986): 1119–1150. 58. Yasnory T. F. Sasaki & Tetsuro Hirose, 3. Tom Maniatis & Bosiljka Tasic, “Alterna- “How to build a paraspeckle,” Genome Biol- tive pre-mRNA splicing and proteome ogy 10 (2009): 227. Freely accessible (2011) expansion in metazoans,” Nature 418 at http://genomebiology.com/content/ (2002): 236–243. pdf/gb-2009-10-7-227.pdf 4. Qun Pan, Ofer Shai, Leo J. Lee, Brendan 59. Sylvie Souquere, Guillaume Beauclair, J. Frey & Benjamin J. Blencowe, “Deep Francis Harper, Archa Fox & Gérard Pier- surveying of alternative splicing complex- ron, “Highly-ordered spatial organization ity in the human transcriptome by high- of the structural long noncoding NEAT1 throughput sequencing,” Nature Genetics RNAs within paraspeckle nuclear bodies,” 40 (2008): 1413–1415. Molecular Biology of the Cell (September 5. Eric T. Wang, Rickard Sandberg, Shujun 2010). Freely accessible (2011) at http:// Luo, Irina Khrebtukova, Lu Zhang, Chris- www.molbiolcell.org/cgi/reprint/E10- tine Mayr, Stephen F. Kingsmore, Gary P. 08-0690v1 Schroth & Christopher B. Burge, “Alter- 60. Marcel E. Dinger, Paulo P. Amaral, native isoform regulation in human tissue Timothy R. Mercer & John S. Mattick, transcriptomes,” Nature 456 (2008): 470– “Pervasive transcription of the eukaryotic 476. Freely accessible (2011) at http:// genome: functional indices and conceptual www.ncbi.nlm.nih.gov/pmc/articles/ implications,” Briefings in Functional Ge- PMC2593745/pdf/nihms-72491.pdf nomics and Proteomics 8 (2009): 407–423. 6. Marc Sultan, Marcel H. Schulz, Hugues 61. Jeremy E. Wilusz, Hongjae Sunwoo Richard, Alon Magen, Andreas Klingen- & David L. Spector, “Long noncoding hoff, Matthias Scherf, Martin Seifert, Tat- RNAs: functional surprises from the jana Borodina, Aleksey Soldatov, Dmitri RNA world,” Genes & Development 23 Parkhomchuk, Dominic Schmidt, Sean (2009): 1494–1504. Freely accessible O’Keeffe, Stefan Haas, Martin Vingron, (2011) at http://genesdev.cshlp.org/con- Hans Lehrach & Marie-Laure Yaspo, “A tent/23/13/1494.full.pdf+html Global View of Gene Activity and Al- 62. Jeannie T. Lee, “Lessons from X-chromo- ternative Splicing by Deep Sequencing some inactivation: long ncRNA as guides of the Human Transcriptome,” Science and tethers to the epigenome,” Genes & 321 (2008): 956–960. Available online Development 23 (2009): 1831–1842. Freely with registration (2011) at http://www. accessible (2011) at http://genesdev.cshlp. sciencemag.org/content/321/5891/956. org/content/23/16/1831.full.pdf+html short 7. Timothy W. Nilsen & Brenton R. Grave- ley, “Expansion of the eukaryotic proteome 125 / Notes 4. Introns and the Splicing Code

by alternative splicing,” Nature 463 (2010): biomedcentral.com/content/pdf/1471- 457–463. 2393-7-S1-S13.pdf 8. Kevin P. Rosenblatt, Zhong-Ping 15. Stefan Hoppler & Claire Louise Kava- Sun, Stefan Heller & A. J. Hud- nagh, “Wnt signalling: variety at the core,” speth, “Distribution of Ca 2+-activated Journal of Cell Science 120 (2007): 385–93. K+ channel isoforms along the tonotopic Freely accessible (2011) at http://jcs.biolo- gradient of the chicken’s cochlea,” Neuron gists.org/cgi/reprint/120/3/385 19 (1997): 1061–1075. 16. Antonino Belfiore, Francesco Frasca, 9. Dhasakumar S. Navaratnam, Thomas J. Giuseppe Pandini, Laura Sciacca & Ric- Bell, Tu Dinh Tu, Erik L. Cohen & J. Carl cardo Vigneri, “Insulin Receptor Isoforms Oberholtzer, “Differential distribution of and Insulin Receptor/Insulin-like Growth Ca 2+-activated K+ channel splice variants Factor Receptor Hybrids in Physiol- among hair cells along the tonotopic axis ogy and Disease,” Endocrine Reviews 30 of the chick cochlea,” Neuron 19 (1997): (2009): 586–623. Freely accessible (2011) 1077–1085. at http://edrv.endojournals.org/cgi/re- 10. Dietmar Schmucker, James C. Clem- print/30/6/586 ens, Huidy Shu, Carolyn A. Worby, Jian 17. Ludmila Prokunina-Olsson, Cullan Xiao, Marco Muda, Jack E. Dixon & S. Welch, Ola Hansson, Neeta Adhikari, Lawrence Zipursky, “Drosophila Dscam Laura J. Scott, Nicolle Usher, Maurine is an axon guidance receptor exhibiting Tong, Andrew Sprau, Amy Swift, Lori L. extraordinary molecular diversity,” Cell 101 Bonnycastle, Michael R. Erdos, Zhi He, (2000): 671–684. Richa Saxena, Brennan Harmon, Olga 11. Kerry Kornfeld, Robert B. Saint, Philip Kotova, Eric P. Hoffman, David Altshuler, A. Beachy, Peter J. Harte, Debra A. Peat- Leif Groop, Michael Boehnke, Francis tie & David S. Hogness, “Structure and S. Collins & Jennifer L. Hall, “Tissue- expression of a family of Ultrabithorax specific alternative splicing ofTCF7L2 ,” mRNAs generated by alternative splicing Human Molecular Genetics 18 (2009): and polyadenylation in Drosophila,” Genes 3795–3804. Freely accessible (2011) at & Development 3 (1989): 243–258. Freely http://hmg.oxfordjournals.org/cgi/re- accessible (2011) at http://genesdev.cshlp. print/18/20/3795 org/content/3/2/243.long 18. Chiharu Sogawa, Chieko Mitsuhata, 12. K. Moriarty, K. H. Kim and J. R. Bender, Kei Kumagai-Morioka, Norio Sogawa, “Minireview: Estrogen Receptor-Mediated Kazumi Ohyama, Katsuya Morita, Kat- Rapid Signaling,” Endocrinology 147 suyuki Kozai, Toshihiro Dohi & Shigeo (2006): 5557–5563. Freely accessible Kitayama, “Expression and Function of (2011) at http://endo.endojournals.org/ Variants of Human Catecholamine Trans- cgi/reprint/147/12/5557 porters Lacking the Fifth Transmembrane 13. Benjamin J. Blencowe, “Alternative splic- Region Encoded by Exon 6,” PLoS One ing: new insights from global analyses,” 5:8 (2010): e11945. Freely accessible (2011) at http://www.plosone.org/article/ Cell 126 (2006): 37–47. info%3Adoi%2F10.1371%2Fjournal. 14. Alison Jane Tyson-Capper, “Alternative pone.0011945 splicing: an important mechanism for myometrial gene regulation that can be 19. Anna Kuta, Wenhan Deng, Ali Morsi manipulated to target specific genes associ- El-Kadi, Gareth T. Banks, Majid Hafez- parast, K. Kevin Pfister & Elizabeth M. C. ated with preterm labour,” BMC Pregnancy Fisher, “Mouse Cytoplasmic Dynein In- Childbirth 7 Supplement 1 (2007): S13. Freely accessible (2011) at http://www. termediate Chains: Identification of New 126 / Notes 4. Introns and the Splicing Code

Isoforms, Alternative Splicing and Tissue Freely accessible (2011) at http://nar.ox- Distribution of Transcripts,” PLoS One fordjournals.org/content/33/2/714.full. 5:7 (2010): e11682. Freely accessible (2011) pdf+html at http://www.plosone.org/article/ 25. Charles W. Sugnet, Karpagam Srini- info%3Adoi%2F10.1371%2Fjournal. vasan, Tyson A. Clark, Georgeann pone.0011682 O’Brien, Melissa S. Cline, Hui Wang, 20. Ahmet Ucar, Vida Vafaizadeh, Huber- Alan Williams, David Kulp, John E. tus Jarry, Jan Fiedler, Petra A. B. Klemmt, Blume, David Haussler & Manuel Ares Thomas Thum, Bernd Groner & Kamal Jr., “Unusual Intron Conservation near Chowdhury, “miR-212 and miR-132 are Tissue-regulated Exons Found by Splicing required for epithelial stromal interactions Microarrays,” PLoS Computational Biology necessary for mouse mammary gland 2:1 (2006): e4. Freely accessible (2011) at development,” Nature Genetics 42 (2010): http://www.ploscompbiol.org/article/ 1101–1108. info%3Adoi%2F10.1371%2Fjournal. 21. Tim R. Mercer, Marcel E. Dinger, pcbi.0020004 Cameron P. Bracken, Gabriel Kolle, Jan 26. Andrea N. Ladd and Thomas A. Cooper, M. Szubert, Darren J. Korbie, Marjan “Finding signals that regulate alternative E. Askarian-Amiri, Brooke B. Gardiner, splicing in the post-genomic era,” Genome Gregory J. Goodall, Sean M. Grimmond Biology 3:11 (2002): reviews0008. Freely & John S. Mattick, “Regulated post- accessible (2011) at http://genomebiol- transcriptional RNA cleavage diversifies ogy.com/content/pdf/gb-2002-3-11- the eukaryotic transcriptome,” Genome reviews0008.pdf Research 20 (2010): 1639–1650. 27. Jingyi Hui, Lee-Hsueh Hung, Monika 22. Vidisha Tripathi, Jonathan D. Ellis, Heiner, Silke Schreiner, Norma Neumül- Zhen Shen, David Y. Song, Qun Pan, ler, Gregor Reither, Stefan A Haas & Andrew T. Watt, Susan M. Freier, C. Albrecht Bindereif, “Intronic CA-repeat Frank Bennett, Alok Sharma, Paula A. and CA-rich elements: a new class of regu- Bubulya, Benjamin J. Blencowe, Supriya G. lators of mammalian alternative splicing,” Prasanth & Kannanganattu V. Prasanth, EMBO Journal 24 (2005): 1988–1998. “The nuclear-retained noncoding RNA Freely accessible (2011) at http://www. MALAT1 regulates alternative splicing by nature.com/emboj/journal/v24/n11/ modulating SR splicing factor phosphory- pdf/7600677a.pdf lation,” Molecular Cell 39 (2010): 925–938. 28. Helder I. Nakaya, Paulo P. Amaral, 23. Rotem Sorek & Gil Ast, “Intronic Rodrigo Louro, André Lopes, Angela A. Sequences Flanking Alternatively Fachel, Yuri B. Moreira, Tarik A. El-Jundi, Spliced Exons Are Conserved between Aline M. da Silva, Eduardo M. Reis & Ser- Human and Mouse,” Genome Research gio Verjovski-Almeida, “Genome mapping 13 (2003): 1631–1637. Freely accessible and expression analyses of human intronic (2011) at http://genome.cshlp.org/con- noncoding RNAs reveal tissue-specific tent/13/7/1631.full.pdf+html patterns and enrichment in genes related 24. Simon Minovitsky, Sherry L. Gee, to regulation of transcription,” Genome Shiruyeh Schokrpur, Inna Dubchak & Biology 8:3 (2007): R43. Freely accessible John G. Conboy, “The splicing regulatory (2011) at http://www.ncbi.nlm.nih.gov/ element, UGCAUG, is phylogenetically pmc/articles/PMC1868932/pdf/gb- and spatially conserved in introns that 2007-8-3-r43.pdf flank tissue-specific alternative exons,” 29. Michelle L. Hastings, Catherine M. Nucleic Acids Research 33 (2005): 714–724. Wilson & Stephen H. Munroe, “A purine- 127 / Notes 4. Introns and the Splicing Code

rich intronic element enhances alternative cessible (2011) at http://nar.oxfordjournals. splicing of thyroid hormone receptor org/content/early/2010/08/04/nar.gkq679. mRNA,” RNA 7 (2001): 859–874. Freely full.pdf+html accessible (2011) at http://www.ncbi.nlm. 36. Shengdong Ke & Lawrence A. Chasin, nih.gov/pmc/articles/PMC1370135/ “Intronic motif pairs cooperate across exons pdf/11421362.pdf to promote pre-mRNA splicing,” Genome 30. Shingo Nakahata & Sachiyo Kawamoto, Biology 11 (2010): R84. Freely accessible “Tissue-dependent isoforms of mammalian (2011) at http://genomebiology.com/ Fox-1 homologs are associated with tissue- content/pdf/gb-2010-11-8-r84.pdf specific splicing activities,”Nucleic Acids 37. Yoseph Barash, John A. Calarco, Weijun Research 33 (2005): 2078–2089. Freely Gao, Qun Pan, Xinchen Wang, Ofer Shai, accessible (2011) at http://www.ncbi.nlm. Benjamin J. Blencowe & Brendan J. Frey nih.gov/pmc/articles/PMC1075922/ “Deciphering the splicing code,” Nature 465 pdf/gki338.pdf (2010): 53–59. 31. Eric J. Wagner, Andrew P. Baraniak, 38. Amir Ali Abbasi, Zissis Paparidis, Sa- October M. Sessions, David Mauger, jid Malik, Debbie K. Goode, Heather Eric Moskowitz & Mariano A. Garcia- Callaway, Greg Elgar & Karl-Heinz Blanco, “Characterization of the Intronic Grzeschik, “Human GLI3 Intragenic Splicing Silencers Flanking FGFR2 Exon Conserved Non-Coding Sequences Are IIIb,” Journal of Biological Chemistry 280 Tissue-Specific Enhancers,”PLoS One (2005): 14017–14027. Freely accessible 2:4 (2007): e366. Freely accessible (2011) (2011) at http://www.jbc.org/con- at http://www.plosone.org/article/ tent/280/14/14017.full.pdf+html info%3Adoi%2F10.1371%2Fjournal. 32. Roberto Marcucci, Francisco E. Baralle pone.0000366 & Maurizio Romano, “Complex splicing 39. Rodrigo Louro, Tarik El-Jundi, Helder control of the human Thrombopoietin I. Nakaya, Eduardo M. Reis & Sergio gene by intronic G runs,” Nucleic Acids Verjovski-Almeida, “Conserved tissue Research 35 (2007): 132–142. Freely acces- expression signatures of intronic noncod- sible (2011) at http://www.ncbi.nlm.nih. ing RNAs transcribed from human and gov/pmc/articles/PMC1802585/pdf/ mouse loci,” Genomics 92 (2008): 18–25. gkl965.pdf 40. Marc P. Hoeppner, Simon White, Dan- 33. Zefeng Wang & Christopher B. Burge, iel C. Jeffares & Anthony M. Poole, “Evo- “Splicing regulation: from a parts list of lutionarily Stable Association of Intronic regulatory elements to an integrated snoRNAs and microRNAs with Their splicing code,” RNA 14 (2008): 802–813. Host Genes,” Genome Biology and Evolu- Freely accessible (2011) at http://rnajour- tion 2009 (2009): 420–428. Freely acces- nal.cshlp.org/content/14/5/802.full. sible (2011) at http://www.ncbi.nlm.nih. pdf+html gov/pmc/articles/PMC2817437/pdf/ 34. John W. S. Brown, David F. Marshall & evp045.pdf Manuel Echeverria, “Intronic noncoding 41. Luis M. Mendes Soares & Juan Valcárcel, RNAs and splicing,” Trends in Plant Sci- “The expanding transcriptome: the genome ence 13 (2008): 335–342. as the ‘Book of Sand,’” EMBO Journal 35. Ji Wen, Akira Chiba & Xiaodong Cai, 25 (2006): 923–931. Available online “Computational identification of tissue- with registration (2011) at http://www. specific alternative splicing elements in nature.com/emboj/journal/v25/n5/ mouse genes from RNA-Seq,” Nucleic full/7601023a.html Acids Research (August 4, 2010). Freely ac- 128 / Notes 4. Introns and the Splicing Code

42. Antony Rodriguez, Sam Griffiths-Jones, (2011) at http://www3.interscience.wiley. Jennifer L. Ashurst & Allan Bradley, com/cgi-bin/fulltext/121391302/PDF- “Identification of Mammalian MicroRNA START Host Genes and Transcription Units,” 49. Christopher J. Ott, Neil P. Blackledge, Genome Research 14 (2004): 1902–1910. Jenny L. Kerschner, Shih-Hsing Leir, Freely accessible (2011) at http://genome. Gregory E. Crawford, Calvin U. Cot- cshlp.org/content/14/10a/1902.full. ton &Ann Harris, “Intronic enhancers pdf+html coordinate epithelial-specific looping of 43. Scott Baskerville & David P. Bartel, “Mi- the active CFTR locus,” Proceedings of the croarray profiling of microRNAs reveals National Academy of Sciences USA 106 frequent coexpression with neighboring (2009): 19934–19939. Freely accessible miRNAs and host genes,” RNA 11 (2005): (2011) at http://www.pnas.org/con- 241–247. Freely accessible (2011) at http:// tent/106/47/19934.full.pdf+html rnajournal.cshlp.org/content/11/3/241. 50. Hani Alotaibi, Elif Yaman, Domenico full.pdf+html Salvatore, Valeria Di Dato, Pelin Tel- 44. Young-Kook Kim & V. Narry Kim, koparan, Roberto Di Lauro & Uygar H. “Processing of intronic microRNAs,” Tazebay, “Intronic elements in the Na+/I- EMBO Journal 26 (2007): 775–783. symporter gene (NIS) interact with reti- Freely accessible (2011) at http://www. noic acid receptors and mediate initiation nature.com/emboj/journal/v26/n3/ of transcription,” Nucleic Acids Research pdf/7601512a.pdf 38 (2010): 3172–3185. Freely accessible 45. S. Hani Najafi-Shoushtari, Fjoralba (2011) at http://nar.oxfordjournals.org/ Kristo, Yingxia Li, Toshi Shioda, David cgi/reprint/38/10/3172 E. Cohen, Robert E. Gerszten & Anders 51. Eric I. Campos & Danny Reinberg, M. Näär, “MicroRNA-33 and the SREBP “Histones: annotating chromatin,” Annual Host Genes Cooperate to Control Cho- Review of Genetics 43 (2009): 559–599. lesterol Homeostasis,” Science 328 (2010): 52. Natalia Soshnikova & Denis Duboule, 1566–1569. “Epigenetic Temporal Control of Mouse 46. Alex Mas Monteys, Ryan M. Spengler, Ji Hox Genes in Vivo,” Science 324 (2009): Wan, Luis Tecedor, Kimberly A. Lennox, 1320–1323. Available online with registra- Yi Xing & Beverly L. Davidson, “Structure tion (2011) at http://www.sciencemag. and activity of putative intronic miRNA org/cgi/content/full/324/5932/1320 promoters,” RNA 16 (2010): 495–505. 53. M. R. Hübner & D. L. Spector, “Chro- Freely accessible (2011) at http://rnajour- matin dynamics,” Annual Review of Bio- nal.cshlp.org/content/16/3/495.long physics 39 (2010): 471–489. 47. Michael Bulger & Mark Groudine, “En- 54. S. A. Lavrov & M. V. Kibanov, “Noncod- hancers: The abundance and function of ing RNAs and Chromatin Structure,” Bio- regulatory sequences beyond promot- chemistry (Moscow) 72 (2007): 1422–1438. ers,” Developmental Biology 339 (2010): Freely accessible (2011) at http://protein. 250–257. bio.msu.ru/biokhimiya/contents/v72/ 48. Shawn P. Grogan, Tsaiwei Olee, Koji pdf/bcm_1422.pdf Hiraoka & Martin K. Lotz, “Repression 55. Antonio Rodríguez-Campos & Fer- of Chondrogenesis through Binding of nando Azorín, “RNA Is an Integral Com- Notch Signaling Proteins HES-1 and ponent of Chromatin that Contributes to HEY-1 to N-box Domains in the COL2A1 Its Structural Organization,” PLoS One Enhancer Site,” Arthritis & Rheumatism 2:11 (2007): e1182. Freely accessible (2011) 58 (2008): 2754–2763. Freely accessible at http://www.plosone.org/article/ 129 / Notes 5. Pseudogenes–Not So Pseudo after All

info%3Adoi%2F10.1371%2Fjournal. 5. Pseudogenes–Not So pone.0001182 Pseudo after All 56. Barbora Malecová & Kevin V Morris, 1. C. Jacq, J. R. Miller & G. G. Brownlee, “A “Transcriptional gene silencing through pseudogene structure in 5S DNA of Xeno- epigenetic changes mediated by non-cod- pus laevis,” Cell 12 (1977): 109–120. ing RNAs,” Current Opinion in Molecular 2. Nick Proudfoot, “Pseudogenes,” Nature Therapeutics 12 (2010): 214–222. Freely 286 (1980): 840–841. accessible (2011) at http://www.ncbi.nlm. 3. C. Deborah Wilde, “Pseudogenes,” nih.gov/pmc/articles/PMC2861437/ Critical Reviews in Biochemistry 19 (1986): pdf/nihms195819.pdf 323–352. 57. Daniel P. Caley, Ryan C. Pink, Daniel 4. ZhaoLei Zhang & Mark Gerstein, “Large- Trujillano & David R. F. Carter, “Long scale analysis of pseudogenes in the human noncoding RNAs, chromatin, and devel- genome,” Current Opinion in Genetics & opment,” 10 (2010): ScientificWorldJournal Development 14 (2004): 328–335. 90–102. 5. Rajkumar Sasidharan & Mark Gerstein, 58. Tanmoy Mondal, Markus Rasmussen, “Protein fossils live on as RNA,” Nature 453 Gaurav Kumar Pandey, Anders Isaksson (2008): 729–731. & Chandrasekhar Kanduri, “Character- 6. Kenneth R. Miller, ization of the RNA content of chromatin,” Only a Theory: Evolu- tion and the Battle for America’s Soul (New Genome Research 20 (2010): 899–907. York: Viking, 2008), pp. 97–98. Freely accessible (2011) at http://genome.cshlp.org/content/20/7/899.full. 7. Douglas J. Futuyma, Evolution (Sunder- pdf+html land, MA: Sinauer Associates, 2005), p. 530. 59. W. F. Chen, K. H. Low, C. Lim & I. Ed- ery, “Thermosensitive splicing of a clock 8. Jerry A. Coyne, Why Evolution Is True gene and seasonal adaptation,” Cold Spring (New York: Viking, 2009), pp. 66–67. Harbor Symposia on Quantitative Biology 72 9. Richard Dawkins, The Greatest Show on (2007): 599–606. Earth: The Evidence for Evolution (New 60. Dan Xia, Xinxin Huang & Hong Zhang, York: Free Press, 2009), pp. 332–333. “The temporally regulated transcription 10. John C. Avise, Inside the Human Genome: factor sel-7 controls developmental timing A Case for Non-Intelligent Design (Oxford: in C. elegans,” Developmental Biology 332 Oxford University Press, 2010), p. 115. (2009): 246–257. 11. Ilenia D’Errico, Gemma Gadaleta & 61. David Gubb, “Intron-Delay and the Cecilia Saccone, “Pseudogenes in metazoa: Precision of Expression of Homeotic Gene Origin and features,” Briefings in Func- Products in Drosophila,” Developmental tional Genomics and Proteomics 3 (2004): Genetics 7 (1986): 119–131. 157–167. Freely accessible (2011) at http:// 62. Carl S. Thummel, “Mechanisms of Tran- bfgp.oxfordjournals.org/cgi/reprint/3/2 scriptional Timing in Drosophila,” Science /157?view=long&pmid=15355597 255 (1992): 39–40. 12. Thierry Tchénio, Evelyne Segal-Bendird- 63. Ian A. Swinburne & Pamela A. Silver, jian & Thierry Heidmann, “Generation “Intron Delays and Transcriptional Tim- of processed pseudogenes in murine cells,” ing During Development,” Developmental EMBO Journal 12 (1993): 1487–1497. Cell 14 (2008): 324–330. Freely accessible Freely accessible (2011) at http:// (2011) at http://www.ncbi.nlm.nih.gov/ www.ncbi.nlm.nih.gov/pmc/articles/ pmc/articles/PMC2825037/pdf/ni- PMC413361/pdf/emboj00076-0228. hms176861.pdf pdf 130 / Notes 5. Pseudogenes–Not So Pseudo after All

13. H.-H. M. Dahl, R. M. Brown, W. M. 20. Rainer Fürbass & Jens Vanselow, “An Hutchison, C. Maragos & G. K. Brown, aromatase pseudogene is transcribed in “A testis-specific form of the human pyru- the bovine placenta,” Gene 154 (1995): vate dehydrogenase E1 alpha subunit is 287–291. coded for by an intronless gene on chromo- 21. D. Aubert, C. Nisanz-Sever & M. Her- some 4,” Genomics 8 (1990): 225–232. zog, “Mitochondrial rps14 is a transcribed 14. J. Sorge, E. Gross, C. West & E. Beu- and edited pseudogene in Arabidopsis thali- tlert, “High level transcription of the ana,” Plant Molecular Biology 20 (1992): glucocerebrosidase pseudogene in nor- 1169–1174. mal subjects and patients with Gaucher 22. V. Quiñones, S. Zanlungo, A. Moenne, disease,” Journal of Clinical Investigation I. Gómez, L. Holuigue, S. Litvak & X. 86 (1990): 1137–1141. Freely accessible Jordana, “The rpl5-rps14-cob gene ar- (2011) at http://www.jci.org/articles/ rangement in Solanum tuberosum: rps14 is view/114818 a transcribed and unedited pseudogene,” 15. I. Touitou, Q. Q. Cai & H. Rochefort, Plant Molecular Biology 31 (1996) 937–943. “17 beta Hydroxysteroid dehydrogenase 1 23. Deyou Zheng, Zhaolei Zhang, Paul M. ‘pseudogene’ is differentially transcribed: Harrison, John Karro, Nick Carriero & still a candidate for the breast-ovarian Mark Gerstein, “Integrated pseudogene cancer susceptibility gene (BRCA1),” Bio- annotation for human chromosome 22: chemical and Biophysical Research Commu- evidence for transcription,” Journal of Mo- nications 201 (1994): 1327–1332. lecular Biology 349 (2005): 27–45. 16. Cornelia Schmutzler & Hans J. Gross, 24. Paul M. Harrison, Deyou Zheng, Zhao- “Genes, variant genes, and pseudogenes of lei Zhang, Nicholas Carriero & Mark Ger- the human tRNAVal gene family are dif- stein, “Transcribed processed pseudogenes ferentially expressed in HeLa cells and in in the human genome: an intermediate human placenta,” Nucleic Acids Research form of expressed retrosequence lacking 18 (1990): 5001–5008. Freely accessible protein-coding ability,” Nucleic Acids Re- (2011) at http://www.ncbi.nlm.nih. search 33 (2005): 2374–2383. Freely acces- gov/pmc/articles/PMC332105/pdf/ sible (2011) at http://nar.oxfordjournals. nar00201-0021.pdf org/cgi/content/full/33/8/2374 17. Yasemin Kaçar, Hildburg Beier & Hans 25. Deyou Zheng, Adam Frankish, Robert J. Gross, “The presence of tRNA pseudo- Baertsch, Philipp Kapranov, Alexandre genes in mammalia and plants and their Reymond, Siew Woh Choo, Yontao Lu, absence in yeast may account for different France Denoeud, Stylianos E. Antonara- specificities of pre-tRNA processing en- kis, Michael Snyder, Yijun Ruan, Chia-Lin zymes,” Gene 156 (1995): 129–132. Wei, Thomas R. Gingeras, Roderic Guigó, 18. Erich T. Boger, James R. Sellers & Jennifer Harrow & Mark B. Gerstein, Thomas B. Friedman, “Human myosin “Pseudogenes in the ENCODE regions: XVBP is a transcribed pseudogene,” Jour- Consensus annotation, analysis of tran- nal of Muscle Research and Cell Motility 22 scription, and evolution,” Genome Research (2001): 477–483. 17 (2007): 839–851. Freely accessible 19. Richard J. Cristiano, Sara J. Giordano (2011) at http://genome.cshlp.org/con- & Alan W. Steggles, “The Isolation and tent/17/6/839.long Characterization of the Bovine Cyto- 26. Michael J. Chorney, Ikuhisa Swada, Ger-

chrome b5 Gene, and a Transcribed Pseu- ald A. Gillespie, Rakesh Srivastava, Julian dogene,” Genomics 17 (1993):348–354. Pan & Sherman M. Weissman, “Tran- scription Analysis, Physical Mapping, and 131 / Notes 5. Pseudogenes–Not So Pseudo after All

Molecular Characterization of a Nonclas- ings of the Royal Society (London) B 244 sical Human Leukocyte Antigen Class I (1991): 151–159. Gene,” Molecular and Cellular Biology 10 34. Manyuan Long & Charles H. Langley, (1990): 243–253. Freely accessible (2011) “Natural Selection and the Origin of jingwei, at http://mcb.asm.org/cgi/reprint/10/1/ a Chimeric Processed Functional Gene in 243?view=long&pmid=2294403 Drosophila,” Science 260 (1993): 91–95. 27. Tuan Nguyen, Roger Sunahara, Adriano 35. Evgeniy S. Balakirev & Francisco J. Marchese, Hubert H. M. Van Tol, Philip Ayala, “Is Esterase-P Encoded by a Cryptic Seeman & Brian F. O’Dowd, “Transcrip- Pseudogene in Drosophila melanogaster?” tion of a human dopamine D5 pseudogene,” Genetics 144 (1996): 1511–1518. Freely Biochemical and Biophysical Research Com- accessible (2011) at http://www.genetics. munications 181 (1991): 16–21. org/cgi/reprint/144/4/1511 28. Jonathan A. Bard, Stanley P. Nawos- 36. M. M. Dumancic, J. G. Oakeshott, R. J. chik, Brian F. O’Dowd, Susan R. George, Russell & M. J. Healy, “Characterization Theresa A. Branchek & Richard L. Wein- of the EstP protein in Drosophila melano- shank, “The human serotonin 5-hydroxy- gaster and its conservation in drosophilids,” tryptamine1D receptor pseudogene is Biochemical Genetics 35 (1997): 251–271. transcribed,” Gene 153 (1995): 295–296. 37. Herman A. Dierick, Julian F. B. Mercer 29. Christine Pourcel, Jean Jaubert, Mi- & Thomas W. Glover, “A phosphoglyc- chelle Hadchouel, Xue Wu & Johannes erate mutase brain isoform (PGAM 1) Schweizer, “A new family of genes and pseudogene is localized within the human pseudogenes potentially expressing testis- Menkes disease gene (ATP7 A),” Gene 198 and brain-specific leucine zipper proteins (1997): 37–41. in man and mouse,” Gene 249 (2000): 38. Esther Betrán, Wen Wang, Li Jin & 105–113. Manyuan Long, “Evolution of the Phos- 30. Mustapha Kandouz, Andrew Bier, phoglycerate Mutase Processed Gene in George D. Carystinos, Moulay A. Alaoui- Human and Chimpanzee Revealing the Jamali and Gerald Batist, “Connexin43 Origin of a New Primate Gene,” Molecular pseudogene is expressed in tumor cells Biology and Evolution 19 (2002): 654–663. and inhibits growth,” Oncogene 23 (2004): Freely accessible (2011) at http://mbe. 4763–4770. oxfordjournals.org/cgi/content/ 31. Markus Koller & Emanuel E. Strehler, full/19/5/654 “Characterization of an intronless human- 39. Agnès Moreau-Aubry, Soizic Le Guiner, calmodulin-like pseudogene,” FEBS Letters Nathalie Labarrière, Marie-Claude Gesnel, 239 (1998): 121–128. Francine Jotereau & Richard Breathnach, 32. Paul Yaswen, Amy Smoll, Junko Hosoda, “A Processed Pseudogene Codes for a New Gordon Parry & Martha R. Stampfer, Antigen Recognized by a CD8+ T Cell “Protein product of a human intronless Clone on Melanoma,” Journal of Experi- calmodulin-like gene shows tissue-specific mental Medicine 191 (2000): 1617–1624. expression and reduced abundance in Freely accessible (2011) at http://jem. transformed cells,” Cell Growth & Differen- rupress.org/content/191/9/1617.full. tiation 3 (1992): 335–345. Freely accessible pdf+html (2010) at http://cgd.aacrjournals.org/ 40. Bing-Sen Zhou, David R. Beidler & cgi/reprint/3/6/335 Yung-Chi Cheng, “Identification of Anti- 33. Pete Jeffs & Michael Ashburner, “Pro- sense RNA Transcripts from a Human cessed pseudogenes in Drosophila,” Proceed- DNA Topoisomerase I Pseudogene,” Can- cer Research 52 (1992): 4280–4285. Freely 132 / Notes 5. Pseudogenes–Not So Pseudo after All

accessible (2011) at http://cancerres.aacr- Murchison, Sihem Cheloufi, Emily Hodg- journals.org/cgi/reprint/52/15/4280 es, Martin Anger, Ravi Sachidanandam, 41. Dominique Weil, Mary-Anne Power, Richard M. Schultz & Gregory J. Hannon, Graham C. Webb & Chung Leung Li, “Pseudogene-derived small interfering “Antisense transcription of a murine FGFR- RNAs regulate gene expression in mouse 3 pseudogene during fetal development,” oocytes,” Nature 453 (2008): 534–538. Gene 187 (1997): 115–122. 49. Xingyi Guo, Zhaolei Zhang, Mark 42. Andrew Fire, SiQun Xu, Mary K. Mont- B. Gerstein & Deyou Zheng, “Small gomery, Steven A. Kostas, Samuel E. Driv- RNAs Originated from Pseudogenes: er & Craig C. Mello, “Potent and specific cis- or trans-Acting?” PLos Computa- genetic interference by double-stranded tional Biology 5:7 (2009): e1000449. RNA in Caenorhabditis elegans,” Nature Freely accessible (2011) at http:// 391 (1998): 806–811. www.ploscompbiol.org/article/ 43. Elisabetta Ullu, Appolinaire Djikeng, info%3Adoi%2F10.1371%2Fjournal. Huafang Shi & Christian Tschudi, “RNA pcbi.1000449 interference: advances and questions,” 50. Shinji Hirotsune, Noriyuki Yoshida, Philosophical Transactions of the Royal Soci- Amy Chen, Lisa Garrett, Fumihiro ety of London B 357 (2002): 65–70. Freely Sugiyama, Satoru Takahashi, Ken-ichi accessible (2011) at http://rstb.royalsoci- Yagami, Anthony Wynshaw-Boris & At- etypublishing.org/content/357/1417/65. sushi Yoshiki, “An expressed pseudogene long regulates the messenger-RNA stability of 44. Gregory J. Hannon, “RNA interference,” its homologous coding gene,” Nature 423 (2003): 91–96. Nature 418 (2002): 244–251. 45. Gunter Meister & Thomas Tuschl, 51. Yoshihisa Yano, Rintaro Saito, Nori- “Mechanisms of gene silencing by double- yuki Yoshida, Atsushi Yoshiki, Anthony Wynshaw-Boris, Masaru Tomita & Shin- stranded RNA,” Nature 431 (2004): 343–349. ji Hirotsune, “A new role for expressed pseudogenes as ncRNA: regulation of 46. Sergei A. Korneev, Ji-Ho Park & Mi- mRNA stability of its homologous coding chael O’Shea, “Neuronal Expression of gene,” Journal of Molecular Medicine 82 Neural Nitric Oxide Synthase (nNOS) (2004): 414–422. Protein Is Suppressed by an Antisense RNA Transcribed from an NOS Pseu- 52. Ondrej Podlaha and Jianzhi Zhang, “Nonneutral Evolution of the Transcribed dogene,” Journal of Neuroscience 19 (1999): 7711–7720. Freely accessible (2011) at Pseudogene Makorin1-p1 in Mice,” Mo- http://www.jneurosci.org/cgi/content/ lecular Biology and Evolution 21 (2004): full/19/18/7711 2202–2209. Freely accessible (2011) at http://mbe.oxfordjournals.org/cgi/con- 47. Toshiaki Watanabe, Yasushi Totoki, At- tent/full/21/12/2202 sushi Toyoda, Masahiro Kaneda, Satomi Kuramochi-Miyagawa, Yayoi Obata, Hat- 53. Jeannie T. Lee, “Molecular biology: Com- sune Chiba, Yuji Kohara, Tomohiro Kono, plicity of gene and pseudogene,” Nature Toru Nakano, M. Azim Surani, Yoshiyuki 423 (2003): 26–28. Sakaki & Hiroyuki Sasaki, “Endogenous 54. Todd A. Gray, Alison Wilson, Patrick J. siRNAs from naturally formed dsRNAs Fortin & Robert D. Nicholls, “The puta- regulate transcripts in mouse oocytes,” tively functional Mkrn1-p1 pseudogene is Nature 453 (2008): 539–543. neither expressed nor imprinted, nor does 48. Oliver H. Tam, Alexei A. Aravin, Paula it regulate its source gene in trans,” Proceed- Stein, Angelique Girard, Elizabeth P. ings of the National Academy of Sciences 133 / Notes 6. Jumping Genes and Repetitive DNA

USA 103 (2006): 12039–12044. Freely Chromosomal Mapping of the Human accessible (2011) at http://www.pnas.org/ Nonfunctional Gene for L-Gulono- content/103/32/12039.full.pdf+html gamma-lactone Oxidase, the Enzyme for 55. Satoko Kaneko, Ikuko Aki, Kaoru Tsu- L-Ascorbic Acid Biosynthesis Missing da, Kazuyuki Mekada, Kazuo Moriwaki, in Man,” Journal of Biological Chemistry Naoyuki Takahata & Yoko Satta, “Origin 269 (1994): 13685–13688. Freely acces- and Evolution of Processed Pseudogenes sible (2011) at http://www.jbc.org/con- That Stabilize FunctionalMakorin1 tent/269/18/13685.long mRNAs in Mice, Primates and Other 61. Örjan Svensson, Lars Arvestad & Mammals,” Genetics 172 (2006): 2421– Jens Lagergren, “Genome-Wide Survey 2429. Freely accessible (2011) at http:// for Biologically Functional Pseudo- www.ncbi.nlm.nih.gov/pmc/articles/ genes,” PLoS Computational Biology 2:5 PMC1456392/pdf/GEN17242421.pdf (2006): e46. Freely accessible (2011) at 56. José Manuel Franco-Zorrilla, Adrián http://www.ploscompbiol.org/article/ Valli, Marco Todesco, Isabel Mateos, info%3Adoi%2F10.1371%2Fjournal. María Isabel Puga, Ignacio Rubio-Somoza, pcbi.0020046 Antonio Leyva, Detlef Weigel, Juan An- 62. Evgeniy S. Balakirev & Francisco J. Ayala, tonio García & Javier Paz-Ares, “Target “Pseudogenes: Are They ‘Junk’ or Func- mimicry provides a new mechanism for tional DNA?” Annual Review of Genetics regulation of microRNA activity,” Nature 37 (2003): 123–51. Genetics 39 (2007): 1033–1037. 63. Amit N. Khachane & Paul M. Har- 57. Armin P. Piehler, Marit Hellum, Jürgen rison, “Assessing the genomic evidence for J. Wenzel, Ellen Kaminski, Kari Bente conserved transcribed pseudogenes under Foss Haug, Peter Kierulf & Wolfgang E. selection,” BMC Genomics 10 (2009): 435. Kaminski, “The human ABC transporter Freely accessible (2011) at http://www. pseudogene family: Evidence for transcrip- biomedcentral.com/1471-2164/10/435 tion and gene-pseudogene interference,” BMC Genomics 9 (2008): 165. Freely ac- 6. Jumping Genes and cessible (2011) at http://www.biomedcen- Repetitive DNA tral.com/1471-2164/9/165 1. Barbara McClintock, “The Origin and 58. Laura Poliseno, Leonardo Salmena, Behavior of Mutable Loci in Maize,” Pro- Jiangwen Zhang, Brett Carver, William ceedings of the National Academy of Sciences J. Haveman & Pier Paolo Pandolfi, “A USA 36 (1950): 344–355. Freely accessible coding-independent function of gene and (2011) at http://www.pnas.org/con- pseudogene mRNAs regulates tumour tent/36/6/344.full.pdf+html biology,” Nature 465 (2010): 1033–1038. 2. Georgii P. Georgiev, “Mobile genetic ele- 59. Morimitsu Nishikimi & Kunio Yagi, ments in animal cells and their biological “Molecular basis for the deficiency in significance,”European Journal of Biochem- humans of gulonolactone oxidase, a key istry 145 (1984): 203–220. Freely acces- enzyme for ascorbic acid biosynthesis,” sible (2011) at http://www3.interscience. American Journal of Clinical Nutrition 54 wiley.com/cgi-bin/fulltext/120761888/ (1991): 1203S-1208S. Freely accessible PDFSTART (2011) at http://www.ajcn.org/cgi/ 3. Nina Fedoroff, “How jumping genes were reprint/54/6/1203S discovered,” Nature Structural Biology 8 60. Morimitsu Nishikimi, Ryuichi Fuku- (2001): 300–301. Freely accessible (2011) yama, Sinsei Minoshima, Nobuyoshi at http://www.nature.com/nsmb/jour- Shimizu & Kunio Yagi, “Cloning and nal/v8/n4/full/nsb0401_300.html 134 / Notes 6. Jumping Genes and Repetitive DNA

4. David Baltimore, “Viral RNA-dependent roder, Nicole Cloonan, Anita L. Steptoe, DNA Polymerase: RNA-dependent DNA Timo Lassmann, Kazunori Waki, Nadine Polymerase in Virions of RNA Tumour Hornig, Takahiro Arakawa, Hazuki Viruses,” Nature 226 (1970): 1209–1211. Takahashi, Jun Kawai, Alistair R. R. For- 5. Howard M. Temin & Satoshi Mizutani, rest, Harukazu Suzuki, Yoshihide Hayas- “Viral RNA-dependent DNA Polymerase: hizaki, David A. Hume, Valerio Orlando, RNA-dependent DNA Polymerase in Sean M. Grimmond & Piero Carninci, Virions of Rous Sarcoma Virus,” Nature “The regulated retrotransposon transcrip- 226 (1970): 1211–1213. tome of mammalian cells,” Nature Genetics 6. P. M. B. Walker & Anne McLaren, “Frac- 41 (2009): 563–571. tionation of mouse deoxyribonucleic acid 14. Amar Kumar & Jeffrey L. Bennetzen, on hydroxyapatite,” Nature 208 (1965): “Retrotransposons: central players in the 1175–1179. structure, evolution and function of plant 7. Roy J. Britten & D. E. Kohne, “Repeated genomes,” Trends in Plant Science 5 (2000): 509–510. Sequences in DNA,” Science 161 (1968): 529–540. 15. Hidenori Nishihara, Arian F. A. Smit 8. W. G. Flamm, “Highly Repetitive Se- and Norihiro Okada “Functional noncoding sequences derived from SINEs in the quences of DNA in Chromosomes,” Inter- mammalian genome,” national Review of Cytology 32 (1972): 1–51. Genome Research 16 (2006): 864–874. Freely accessible 9. Maxine F. Singer, “SINEs and LINEs: (2011) at http://genome.cshlp.org/con- Highly Repeated Short and Long Inter- tent/16/7/864.full.pdf+html spersed Sequences in Mammalian Ge- 16. Craig B. Lowe, Gill Bejerano & David nomes,” Cell 28 (1982): 433–434. Haussler, “Thousands of human mobile 10. Bruce Alberts, Alexander Johnson, Julian element fragments undergo strong purify- Lewis, Martin Raff, Keith Roberts & ing selection near developmental genes,” Peter Walter, Molecular Biology of the Cell, Proceedings of the National Academy of Sci- Fourth Edition (New York: Garland Sci- ences USA 104 (2007): 8005–8010. Freely ence, 2002), p. 203 accessible (2011) at http://www.pnas.org/ 11. GenBank, “Homo sapiens RNA, 7SL, content/104/19/8005.full.pdf+html cytoplasmic 1 (RN7SL1), small cytoplas- 17. Aristotelis Tsirigos & Isidore Rigoutsos, mic RNA,” NCBI Reference Sequence: “Alu and B1 Repeats Have Been Selectively NR_002715.1 (28 February 2010). Freely Retained in the Upstream and Intronic accessible (2011) at http://www.ncbi.nlm. Regions of Genes of Specific Functional nih.gov/nuccore/NR_002715.1 Classes,” PLoS Computational Biology 5:12 12. Karen L. Bennett, Robert E. Hill, Den- (2009): e1000610. Freely accessible (2011) nis F. Pietras, Mary Woodworth-Gutai, at http://www.ploscompbiol.org/article/ Colleen Kane-Haas, Joanna M. Houston, info%3Adoi%2F10.1371%2Fjournal. John K. Heath & Nicholas D. Hastie, pcbi.1000610 “Most Highly Repeated Dispersed DNA 18. Susumu Ohno, W. D. Kaplan & R. Families in the Mouse Genome,” Molecu- Kinosita, “Formation of the sex chromatin 4 (1984): 1561–1571. lar and Cell Biology by a single X-chromosome in liver cells of Freely accessible (2011) at http://mcb.asm. Rattus norvegicus,” Experimental Cell Re- org/cgi/reprint/4/8/1561?view=long&p search 18 (1959): 415–418. mid=6208477 19. Jeffrey A. Bailey, Laura Carrel, Aravinda 13. Geoffrey J. Faulkner, Yasumasa Kimura, Chakravarti & Evan E. Eichler, “Molecu- Carsten O. Daub, Shivangi Wani, Charles lar evidence for a relationship between Plessy, Katharine M. Irvine, Kate Sch- 135 / Notes 6. Jumping Genes and Repetitive DNA

LINE-1 elements and X chromosome (2011) at http://www.biochemj.org/ inactivation: the Lyon repeat hypothesis,” bj/406/0491/4060491.pdf Proceedings of the National Academy of Sci- 25. Corrado Spadafora, “A reverse transcrip- ences USA 97 (2000): 6634–6639. Freely tase-dependent mechanism plays central accessible (2011) at http://www.pnas.org/ roles in fundamental biological processes,” content/97/12/6634.full.pdf+html Systems Biology in Reproductive Medicine 54 20. Y. Amy Tang, Derek Huntley, Giovanni (2008): 11–21. Montana, Andrea Cerase, Tatyana B. 26. Anderly C. Chueh, Emma L. Northrop, Nesterova & Neil Brockdorff, “Efficiency Kate H. Brettingham-Moore, K. H. of Xist-mediated silencing on autosomes is Andy Choo & Lee H. Wong, “LINE linked to chromosomal domain organiza- Retrotransposon RNA Is an Essential tion,” Epigenetics & Chromatin 3 (2010): Structural and Functional Epigenetic 10. Freely accessible (2011) at http://www. Component of a Core Neocentromeric epigeneticsandchromatin.com/content/ Chromatin,” PLoS Genetics 5:1 (2009): pdf/1756-8935-3-10.pdf e1000354. Freely accessible (2011) at 21. Jennifer C. Chow, Constance Ciaudo, http://www.plosgenetics.org/article/ Melissa J. Fazzari. Nathan Mise, Nicolas info%3Adoi%2F10.1371%2Fjournal. Servant, Jacob L. Glass, Matthew Attreed, pgen.1000354 Philip Avner, Anton Wutz, Emmanuel 27. Dylan R. Edwards, Craig L. J. Parfett Barillot, John M. Greally, Olivier Voin- & David T. Denhardt, “Transcriptional net & Edith Heard, “LINE-1 activity in Regulation of Two Serum-induced RNAs facultative heterochromatin formation in Mouse Fibroblasts: Equivalence of during X chromosome inactivation,” Cell One Species to B2 Repetitive Elements,” 141 (2010): 956–969. Molecular and Cellular Biology 5 (1985): 22. Tammy A. Morrish, Nicolas Gilbert, 3280–3288. Freely accessible (2011) at Jeremy S. Myers, Bethaney J. Vincent, http://mcb.asm.org/cgi/reprint/5/11/3 Thomas D. Stamato, Guillermo E. Tac- 280?view=long&pmid=3837843 cioli, Mark A. Batzer & John V. Moran, 28. Roy J. Brittten, “Coding sequences of “DNA repair mediated by endonuclease- functioning human genes derived entirely independent LINE-1 retrotransposition,” from mobile element sequences,” Proceed- Nature Genetics 31 (2002): 159–165. ings of the National Academy of Sciences 23. José L. Garcia-Perez, Aurélien J. Doucet, USA 101 (2004): 16825–16830. Freely Alain Bucheton, John V. Moran & Nicolas accessible (2011) at http://www.pnas.org/ Gilbert, “Distinct mechanisms for trans- content/101/48/16825.full.pdf+html mediated mobilization of cellular RNAs 29. L. P. Yavachev, O. I. Georgiev, E. A. by the LINE-1 reverse transcriptase,” Ge- Braga, T. A. Avdonina, A. E. Bogomolova, nome Research 17 (2007): 602–611. Freely V. B. Zhurkin, V. V. Nosikov & A. A. accessible (2011) at http://genome.cshlp. Hadjiolov, “Nucleotide sequence analysis org/content/17/5/602.full.pdf+html of the spacer regions flanking the rat 24. Elizabeth A. Shepard, Pritpal Chan- rRNA transcription unit and identifica- dan, Milena Stevanovic-Walker, Mina tion of repetitive elements,” Nucleic Acids Edwards & Ian R. Phillips, “Alternative Research 14 (1986): 2799–2810. Freely promoters and repetitive DNA elements accessible (2011) at http://www.ncbi.nlm. define the species-dependent tissue- nih.gov/pmc/articles/PMC339699/pdf/ specific expression of the FMO1 genes of nar00275-0387.pdf human and mouse,” Biochemical Journal 30. Richard H. Kimura, Prabhakara V. 406 (2007): 491–499. Freely accessible Choudary & Carl W. Schmid, “Silk worm 136 / Notes 6. Jumping Genes and Repetitive DNA

Bm1 SINE RNA increases following cey D. Wagner, Jennifer F. Kugel & James cellular insults,” Nucleic Acids Research A. Goodrich, “Human Alu RNA is a 27 (1999): 3380–3387. Freely accessible modular transacting repressor of mRNA (2011) at http://nar.oxfordjournals.org/ transcription during heat shock,” Molecu- cgi/reprint/27/16/3380 lar Cell 29 (2008): 499–509. 31. Richard H. Kimura, Prabhakara V. 37. Julien Häsler & Katharina Strub, “Alu Choudary, Koni K. Stone & Carl W. RNP and Alu RNA regulate translation Schmid, “Stress induction of Bm1 RNA in initiation in vitro,” Nucleic Acids Research silkworm larvae: SINEs, an unusual class 34 (2006): 2374–2385. Freely accessible of stress genes,” Cell Stress & Chaperones 6 (2011) at http://nar.oxfordjournals.org/ (2001): 263–272. Freely accessible (2011) cgi/reprint/34/8/2374 at http://www.ncbi.nlm.nih.gov/pmc/ 38. Julien Häsler & Katharina Strub, “Alu articles/PMC434408/pdf/i1466-1268-6- elements as regulators of gene expres- 3-263.pdf sion,” Nucleic Acids Research 34 (2006): 32. Phillip A. Yates, Robert W. Burman, 5491–5497. Freely accessible (2011) at Padmaja Mummaneni, Sandra Krussel & http://nar.oxfordjournals.org/cgi/content/ Mitchell S. Turker, “Tandem B1 Elements full/34/19/5491 Located in a Mouse Methylation Center 39. Julien Häsler, T. Samuelsson & Kathari- Provide a Target for de Novo DNA Meth- na Strub, “Useful ‘junk’: Alu RNAs in the ylation,” Journal of Biological Chemistry human transcriptome,” Cellular and Mo- 274 (1999): 36357–36361. Freely acces- lecular Life Sciences 64 (2007): 1793–1800. sible (2011) at http://www.jbc.org/con- 40. Tong J. Gu, Xiang Yi, Xi W. Zhao, Yi tent/274/51/36357.full.pdf+html , Zhao & James Q. Yin “Alu-directed 33. Celso A. Espinoza, Tiffany A. Allen, transcriptional regulation of some novel Aaron R. Hieb, Jennifer F. Kugel & James miRNAs,” BMC Genomics 10 (2009): 563. A. Goodrich, “B2 RNA binds directly to Freely accessible (2011) at http://www. RNA polymerase II to repress transcript biomedcentral.com/1471-2164/10/563 synthesis,” Nature Structural & Molecular 41. Michal Barak, Erez Y. Levanon, Eli Biology 11 (2004): 822–829. Eisenberg, Nurit Paz, Gideon Rechavi, 34. Celso A. Espinoza, James A. Goodrich George M. Church & Ramit Mehr, “Evi- & Jennifer F. Kugel, “Characterization of dence for large diversity in the human the structure, function, and mechanism of transcriptome created by Alu RNA edit- B2 RNA, an ncRNA repressor of RNA ing,” Nucleic Acids Research 37 (2009): polymerase II transcription,” RNA 13 6905–6915. Freely accessible (2011) at (2007): 583–596. Freely accessible (2011) http://nar.oxfordjournals.org/cgi/re- at http://rnajournal.cshlp.org/con- print/37/20/6905 tent/13/4/583.full.pdf+html 42. Ryan D. Walters, Jennifer F. Kugel & 35. Gordon Vansant & Wanda F. Reynolds, James A. Goodrich, “InvAluable junk: the “The consensus sequence of a majorAlu cellular impact and function of Alu and B2 subfamily contains a functional retinoic RNAs,” IUBMB Life 61 (2009): 831–837. acid response element,” Proceedings of 43. Ann L. Boyle, S. Gwyn Ballard & Da- the National Academy of Sciences USA vid C. Ward, “Differential distribution 92 (1995): 8229–8233. Freely accessible of long and short interspersed element (2011) at http://www.pnas.org/consequences in the mouse genome: Chromo- tent/92/18/8229.full.pdf+html some karyotyping by fluorescence in situ 36. Peter D. Mariner, Ryan D. Walters, Cel- hybridization,” Proceedings of the National so A. Espinoza, Linda F. Drullinger, Sta- Academy of Sciences USA 87 (1990): 7757– 137 / Notes 6. Jumping Genes and Repetitive DNA

7761. Freely accessible (2011) at http:// gov/pmc/articles/PMC1255937/pdf/ www.pnas.org/content/87/19/7757.full. nihms3265.pdf pdf+html 51. Zachary Lippman, Anne-Valérie Gen- 44. J. M. Craig & W. A. Bickmore, “Chromo- drel, Michael Black, Matthew W. Vaughn, some bands—flavours to savour,”BioEssays Neilay Dedhia, W. Richard McCombie, 15 (1993): 349–354. Kimberly Lavine, Vivek Mittal, Bruce May, 45. Yataro Daigo, Minoru Isomura, Tadashi Kristin D. Kasschau, James C. Carrington, Nishiwaki, Kazufumi Suzuki, Osamu Rebecca W. Doerge, Vincent Colot & Rob Maruyama, Kumiko Takeuchi, Yuka Martienssen, “Role of transposable ele- Yamane, Rie Hayashi, Maiko Minami, ments in heterochromatin and epigenetic Yoshiaki Hojo, Ikuo Uchiyama, Toshihisa control,” Nature 430 (2004): 471–476. Takagi & Yusuke Nakamura, “Significant 52. Zachary Lippman & Rob Martienssen, Differences in the Frequency of Tran- “The role of RNA interference in hetero- scriptional Units, Types and Numbers of chromatic silencing,” Nature 431 (2004): Repetitive Elements, GC content, and the 364–370. Number of CpG Islands Between a 1010- 53. Victoria V. Lunyak, Gratien G. Pre- kb G-band Genomic Segment on Chro- fontaine, Esperanza Núñez, Thorsten mosome 9q31.3 and a 1200-kb R-band Ge- Cramer, Bong-Gun Ju, Kenneth A. Ohgi, nomic Segment on Chromosome 3p21.3,” Kasey Hutt, Rosa Roy, Angel García-Díaz, DNA Research 6 (1999): 227–233. Freely Xiaoyan Zhu, Yun Yung, Lluís Monto- accessible (2011) at http://dnaresearch. liu, Christopher K. Glass & Michael G. oxfordjournals.org/cgi/reprint/6/4/227 Rosenfeld, “Developmentally regulated ?view=long&pmid=10492169 activation of a SINE B2 repeat as a do- 46. Sam Janssen, Olivier Cuvier, Martin main boundary in organogenesis,” Science Müller & Ulrich K Laemmli, “Specific 317 (2007): 248–251. gain- and loss-of-function phenotypes 54. Ram Parikshan Kumar, Ramamoorthy induced by satellite-specific DNA-binding Senthilkumar, Vipin Singh & Rakesh drugs fed to Drosophila melanogaster,” Mo- K. Mishra, “Repeat performance: how do lecular Cell 6 (2000): 1013–1024. genome packaging and regulation depend 47. Steven Henikoff & Danielle Vermaak, on simple sequence repeats?” BioEssays 32 “Bugs on drugs go GAGAA,” Cell 103 (2010): 165–174. (2000): 695–698. 55. Satoru Ide, Takaaki Miyazaki, Hisaji 48. Mary-Lou Pardue & P. Gregory De- Maki & Takehiko Kobayashi, “Abundance Baryshe, “Drosophila telomeres: two trans- of ribosomal RNA gene copies maintains posable elements with important roles genome integrity,” Science 327 (2010): in chromosomes,” Genetica 107 (1999): 693–696. 189–196. 56. Karen Bohmert, Isabelle Camus, Cath- 49. Mary-Lou Pardue & P. Gregory De- erine Bellini, David Bouchez, Michel Cab- Baryshe, “Drosophila telomere transpo- oche & Christoph Benning, “AGO1 defines sons: genetically active elements in hetero- a novel locus of Arabidopsis controlling leaf chromatin,” Genetica 109 (2000): 45–52. development,” EMBO Journal 17 (1998): 50. M.-L. Pardue, S. Rashkova, E. Casacu- 170–180. Freely accessible (2011) at http:// berta, P. G. DeBaryshe, J. A. George & K. www.ncbi.nlm.nih.gov/pmc/articles/ L. Traverse, “Two retrotransposons main- PMC1170368/pdf/000170.pdf tain telomeres in Drosophila,” Chromosome 57. Michelle A. Carmell, Zhenyu Xuan, Research 13 (2005): 443–453. Freely acces- Michael Q. Zhang & Gregory J. Han- sible (2011) at http://www.ncbi.nlm.nih. non, “The Argonaute family: tentacles that 138 / Notes 6. Jumping Genes and Repetitive DNA

reach into RNAi, developmental control, cells in the Drosophila ovary,” Development stem cell maintenance, and tumorigenesis,” 124 (1997): 2463–2476. Freely accessible Genes & Development 16 (2002): 2733– (2011) at http://dev.biologists.org/con- 2742. Freely accessible (2011) at http:// tent/124/12/2463.long genesdev.cshlp.org/content/16/21/2733. 66. Daniel N. Cox, Anna Chao & Haifan full.pdf+html Lin, “piwi encodes a nucleoplasmic factor 58. Andreas Lingel & Elisa Izaurralde, whose activity modulates the number “RNAi: finding the elusive endonuclease.” and division rate of germline stem cells,” RNA 10 (2004): 1675–1679. Freely acces- Development 127 (2000): 503–514. Freely sible (2011) at http://rnajournal.cshlp. accessible (2011) at http://dev.biologists. org/content/10/11/1675.full.pdf+html org/content/127/3/503.long 59. T. Hall, “Structure and function of 67. Daniel N. Cox, Anna Chao, Jeff Baker, argonaute proteins,” Structure 13 (2005): Lisa Chang, Dan Qiao & Haifan Lin, “A 1403–1408. novel class of evolutionarily conserved 60. George L. Sen & Helen M. Blau, “Argo- genes defined bypiwi are essential for stem naute 2/RISC resides in sites of mamma- cell self-renewal,” Genes & Development lian mRNA decay known as cytoplasmic 12 (1998): 3715–3727. Freely accessible bodies,” Nature Cell Biology 7 (2005): (2011) at http://genesdev.cshlp.org/con- 633–636. tent/12/23/3715.full.pdf+html 61. Tim A. Rand, Sean Petersen, Fenghe 68. Jin-Biao Ma, Yu-Ren Yuan, Gunter Du & Xiaodong Wang, “Argonaute2 Meister, Yi Pei, Thomas Tuschl & Din- cleaves the anti-guide strand of siRNA shaw J. Patel, “Structural basis for 5’-end- during RISC activation,” Cell 123 (2005): specific recognition of guide RNA by 621–629. the A. fulgidus Piwi protein,” Nature 434 62. Robert E. Collins & Xiaodong Cheng, (2005): 666–670. “Structural and Biochemical Advances in 69. Christopher R. Faehnle & Leemor Mammalian RNAi,” Journal of Cellular Joshua-Tor, “Argonautes confront new Biochemistry 99 (2006): 1251–1266. Freely small RNAs,” Current Opinion in Chemical accessible (2011) at http://www.ncbi.nlm. Biology 11 (2007): 569–577. Freely acces- nih.gov/pmc/articles/PMC2688788/ sible (2011) at http://www.ncbi.nlm.nih. pdf/nihms-117419.pdf gov/pmc/articles/PMC2077831/pdf/ 63. Emily Bernstein, Amy A. Caudy, Scott nihms-33482.pdf M. Hammond & Gregory J. Hannon, 70. Julia Höck & Gunter Meister, “The Ar- “Role for a bidentate ribonuclease in the gonaute protein family,” Genome Biology initiation step of RNA interference,” Na- 9:2 (2008): 210. Freely accessible (2011) at ture 409 (2001): 363–366. http://genomebiology.com/content/pdf/ 64. N. Baumberger & D. C. Baulcombe, gb-2008-9-2-210.pdf “Arabidopsis ARGONAUTE1 is an RNA 71. Kuniaki Saito, Kazumichi M. Nishida, Slicer that selectively recruits microRNAs Tomoko Mori, Yoshinori Kawamura, and short interfering RNAs,” Proceedings Keita Miyoshi, Tomoko Nagami, Har- of the National Academy of Sciences USA uhiko Siomi & Mikiko C. Siomi, “Specific 102 (2005): 11928–11933. Freely acces- association of Piwi with rasiRNAs derived sible (2011) at http://www.pnas.org/con- from retrotransposon and heterochromat- tent/102/33/11928.full.pdf+html ic regions in the Drosophila genome,” Genes 65. Haifan Lin & Allan C. Spradling, “A & Development 20 (2006): 2214–2222. Freely accessible (2011) at http://genesdev. novel group of pumilio mutations affects the asymmetric division of germline stem 139 / Notes 6. Jumping Genes and Repetitive DNA

cshlp.org/content/20/16/2214.full. (2011) at http://www.pnas.org/con- pdf+html tent/59/4/1158.full.pdf+html 72. Yoshinori Kawamura, Kuniaki Saito, 79. Harold E. Varmus “Retroviruses,” Science Taishin Kin, Yukiteru Ono, Kiyoshi Asai, 240 (1988): 1427–1435. Takafumi Sunohara, Tomoko N. Okada, 80. Peter N. Rosenthal, Harriet L. Robinson, Mikiko C. Siomi & Haruhiko Siomi, William S. Robinson, Teruko Hanafusa “Drosophila endogenous small RNAs bind & Hidesaburo Hanafusa, “DNA in Unin- to Argonaute 2 in somatic cells,” Nature fected and Virus-Infected Cells Comple- 453 (2008): 793–797. mentary to Avian Tumor Virus RNA,” 73. Megha Ghildiyal, Hervé Seitz, Michael Proceedings of the National Academy of Sci- D. Horwich, Chengjian Li, Tingting Du, ences USA 68 (1971): 2336–2340. Freely Soohyun Lee, Jia Xu, Ellen L.W. Kittler, accessible (2011) at http://www.pnas.org/ Maria L. Zapp, Zhiping Weng & Phil- content/68/10/2336.full.pdf+html lip D. Zamore, “Endogenous siRNAs 81. Harold E. Varmus, Robin A. Weiss, Derived from Transposons and mRNAs Robert R. Friis, Warren Levinson & J. in Drosophila Somatic Cells,” Science 320 Michael Bishop, “Detection of Avian Tu- (2008): 1077–1081. mor Virus-Specific Nucleotide Sequences 74. Haifan Lin, “piRNAs in the germ line,” in Avian Cell DNAs,” Proceedings of the Science 316 (2007): 397. National Academy of Sciences USA 69 75. Travis Thomson & Haifan Lin, “The (1972): 20–24. Freely accessible (2011) at Biogenesis and Function of PIWI Proteins http://www.pnas.org/content/69/1/20. and piRNAs: Progress and Prospect,” full.pdf+html Annual Review of Cell and Developmental 82. Robin A Weiss, “The discovery of endog- Biology 25 (2009): 355–376. Freely acces- enous retroviruses,” Retrovirology 3 (2006): sible (2011) at http://www.ncbi.nlm.nih. 67. Freely accessible (2011) at http://www. gov/pmc/articles/PMC2780330/pdf/ retrovirology.com/content/pdf/1742- nihms158620.pdf 4690-3-67.pdf 76. Christel Rouget, Catherine Papin, An- 83. Motoharu Seiki, Seisuke Hattori & thony Boureux, Anne-Cécile Meunier, Mistuaki Yoshida, “Human adult T-cell Bénédicte Franco, Nicolas Robine, Eric C. leukemia virus: Molecular cloning of the Lai, Alain Pelisson & Martine Simonelig, provirus DNA and the unique terminal “Maternal mRNA deadenylation and structure,” Proceedings of the National decay by the piRNA pathway in the early Academy of Sciences USA 79 (1982): 6899– Drosophila embryo,” Nature 467 (2010): 6902. Freely accessible (2011) at http:// 1128–1132. www.pnas.org/content/79/22/6899.full. 77. Howard M. Temin, “Homology Between pdf+html RNA from Rous Sarcoma Virus and 84. Joseph G. Sodroski, Craig A. Rosen & DNA from Rous Sarcoma Virus-Infected William A. Haseltine, “Trans-acting tran- Cells,” Proceedings of the National Academy scriptional activation of the long terminal of Sciences USA 52 (1964): 323–329. Freely repeat of human T lymphotropic vi- accessible (2011) at http://www.pnas.org/ ruses in infected cells,” Science 225 (1984): content/52/2/323.full.pdf+html 381–385. 78. Heiner Westphal & Renato Dulbecco, 85. Robert G. Ramsay, Shunsuke Ishii & “Viral DNA in Polyoma- and SV40- Thomas J. Gonda, “Interaction of the transformed Cell Lines,” Proceedings of Myb Protein with Specific DNA Bind- the National Academy of Sciences USA ing Sites,” Journal of Biological Chemistry 59 (1968): 1158–1165. Freely accessible 267 (1992): 5656–5662. Freely accessible 140 / Notes 6. Jumping Genes and Repetitive DNA

(2011) at http://www.jbc.org/con- Freely accessible (2011) at http://jvi.asm. tent/267/8/5656.full.pdf+html org/cgi/reprint/76/5/2410 86. Nathalie de Parseval, Hanan Alkab- 92. Elena Gogvadze, Elena Stukacheva, An- bani & Thierry Heidmann, “The long ton Buzdin & Eugene Sverdlov, “Human- terminal repeats of the HERV-H human Specific Modulation of Transcriptional endogenous retrovirus contain binding Activity Provided by Endogenous Ret- sites for transcriptional regulation by the roviral Insertions,” Journal of Virology Myb protein,” Journal of General Virology 83 (2009): 6098–6105. Freely accessible 80 (1999): 841–845. Freely accessible (2011) at http://jvi.asm.org/cgi/re- (2011) at http://vir.sgmjournals.org/cgi/ print/83/12/6098 reprint/80/4/841 93. Catherine A. Dunn, Patrik Medstrand 87. Patrik Medstrand, Josette-Renée Landry & Dixie L. Mager, “An endogenous retro- & Dixie L. Mager, “Long Terminal Re- viral long terminal repeat is the dominant peats Are Used as Alternative Promoters promoter for human b1,3-galactosyltrans- for the Endothelin B Receptor and Apoli- ferase 5 in the colon,” Proceedings of the poprotein C-I Genes in Humans,” Journal National Academy of Sciences USA 100 of Biological Chemistry 276 (2001): 1896– (2003): 12841–12846. Freely accessible 1903. Freely accessible (2011) at http:// (2011) at http://www.pnas.org/con- www.jbc.org/content/276/3/1896.full. tent/100/22/12841.full.pdf+html pdf+html 94. Catherine A. Dunn & Dixie L. Mager, 88. Josette-Renée Landry & Dixie L. Mager, “Transcription of the human and rodent “Functional Analysis of the Endogenous SPAM1 / PH-20 genes initiates within Retroviral Promoter of the Human an ancient endogenous retrovirus,” BMC Endothelin B Receptor Gene,” Journal of Genomics 6 (2005): 47. Freely accessible Virology 77 (2003): 7459–7466. Freely ac- (2011) at http://www.biomedcentral. cessible (2011) at http://jvi.asm.org/cgi/ com/content/pdf/1471-2164-6-47.pdf reprint/77/13/7459 95. Anton Buzdin, Elena Kovalskaya- 89. Anne E. Peaston, Alexei V. Evsikov, Joel Alexandrova, Elena Gogvadze & Eugene H. Graber, Wilhelmine N. de Vries, An- Sverdlov, “At Least 50% of Human-Spe- drea E. Holbrook, Davor Solter & Barbara cific HERV-K (HML-2) Long Terminal B. Knowles, “Retrotransposons regulate Repeats Serve in Vivo as Active Promoters host genes in mouse oocytes and preim- for Host Nonrepetitive DNA Transcrip- plantation embryos,” Developmental Cell 7 tion,” Journal of Virology 80 (2006): 10752– (2004): 597–606. 10762. Freely accessible (2011) at http:// 90. James A. Shapiro, “Retrotransposons jvi.asm.org/cgi/reprint/80/21/10752 and regulatory suites,” BioEssays 27 (2005): 96. Woo Jung Lee, Hyun Jin Kwun & Kyung 122–125. Lib Jang, “Analysis of transcriptional regu- 91. Jianhua Ling, Wenhu Pi, Roni Bollag, latory sequences in the human endogenous Shan Zeng, Meral Keskintepe, Hatem retrovirus W long terminal repeat,” Jour- Saliman, Sanford Krantz, Barry Whitney nal of General Virology 84 (2003): 2229– & Dorothy Tuan, “The Solitary Long 2235. Freely accessible (2011) at http://vir. Terminal Repeats of ERV-9 Endogenous sgmjournals.org/cgi/reprint/84/8/2229 Retrovirus Are Conserved during Primate 97. Andrew B. Conley, Jittima Piriyapongsa Evolution and Possess Enhancer Activities & I. King Jordan, “Retroviral promoters in Embryonic and Hematopoietic Cells,” in the human genome,” Bioinformatics Journal of Virology 76 (2002): 2410–2423. 24 (2008): 1563–1567. Freely accessible 141 / Notes 6. Jumping Genes and Repetitive DNA

(2011) at http://bioinformatics.oxford- Freely accessible (2011) at http://mcb.asm. journals.org/cgi/reprint/24/14/1563 org/cgi/reprint/23/10/3566 98. Ulrike Schön, Olivia Diem, Laura Leit- 103. I. Knerr, B. Huppertz, C. Weigel, J. ner, Walter H. Günzburg, Dixie L. Mager, Dötsch, C. Wich, R. L. Schild, M. W. Brian Salmons & Christine Leib-Mösch, Beckmann & W. Rascher, “Endogenous “Human Endogenous Retroviral Long retroviral syncytin: compilation of ex- Terminal Repeat Sequences as Cell Type- perimental research on syncytin and its Specific Promoters in Retroviral Vectors,” possible role in normal and disturbed hu- Journal of Virology 83 (2009): 12643– man placentogenesis,” Molecular Human 12650. Freely accessible (2011) at http:// Reproduction 10 (2004): 581–588. Freely jvi.asm.org/cgi/reprint/83/23/12643 accessible (2011) at http://molehr.oxford- 99. Patrick J. W. Venables, Sharon M. journals.org/cgi/reprint/10/8/581 Brookes, David Griffiths, Robin A. Weiss 104. Kathrin A. Dunlap, Massimo Palma- & Mark T. Boyd, “Abundance of an en- rini, Mariana Varela, Robert C. Burghardt, dogenous retroviral envelope protein in Kanako Hayashi, Jennifer L. Farmer & placental trophoblasts suggests a biological Thomas E. Spencer, “Endogenous retrovi- function.” Virology 211 (1995): 589–592. ruses regulate periimplantation placental 100. Sha Mi, Xinhua Lee, Xiang-ping growth and differentiation,”Proceedings of Li, Geertruida M. Veldman, Heather the National Academy of Sciences USA 103 Finnerty, Lisa Racie, Edward LaVal- (2006): 14390–14395. Freely accessible lie, Xiang-Yang Tang, Philippe Edouard, (2011) at http://www.pnas.org/con- Steve Howes, James C. Keith Jr. & John tent/103/39/14390.full.pdf+html M. McCoy, “Syncytin is a captive retroviral 105. Ina Knerr, Ernst Beinder & Wolfgang envelope protein involved in human pla- Rascher, “Syncytin, a novel human endog- cental morphogenesis,” Nature 403 (2000): enous retroviral gene in human placenta: 785–789. Evidence for its dysregulation in pre- 101. Jean-Luc Blond, Dimitri Lavillette, eclampsia and HELLP syndrome,” Ameri- Valérie Cheynet, Olivier Bouton, Guy can Journal of Obstetrics and Gynecology 186 Oriol, Sylvie Chapel-Fernandes, Bernard (2002): 210–213. Mandrand, François Mallet & François- 106. Joseph M. Antony, Kristofor K. Ellestad, Loïc Cosset, “An Envelope Glycoprotein Robert Hammond, Kazunori Imaizumi, of the Human Endogenous Retrovirus Francois Mallet, Kenneth G. Warren & HERV-W Is Expressed in the Human Christopher Power, “The Human Endog- Placenta and Fuses Cells Expressing the enous Retrovirus Envelope Glycoprotein, Type D Mammalian Retrovirus Receptor,” Syncytin-1, Regulates Neuroinflammation Journal of Virology 74 (2000): 3321–3329. and its Receptor Expression in Multiple Freely accessible (2011) at http://jvi.asm. Sclerosis: A Role for Endoplasmic Reticu- org/cgi/reprint/74/7/3321 lum Chaperones in Astrocytes,” Journal 102. Jean-Louis Frendo, Delphine Olivier, of Immunology 179 (2007): 1210–1224. Valérie Cheynet, Jean-Luc Blond, Olivier Freely accessible (2011) at http://www. Bouton, Michel Vidaud, Michèle Rabreau, jimmunol.org/cgi/reprint/179/2/1210 Danièle Evain-Brion & François Mal- 107. Sandra Blaise, Nathalie de Parseval, let, “Direct Involvement of HERV-W Env Laurence Bénit & Thierry Heidmann, Glycoprotein in Human Trophoblast Cell “Genomewide screening for fusogenic Fusion and Differentiation,”Molecular human endogenous retrovirus envelopes and Cellular Biology 23 (2003): 3566–3574. identifiessyncytin 2, a gene conserved on primate evolution,” Proceedings of the 142 / Notes 7. Functions Independent of Exact Sequence

National Academy of Sciences USA 100 112. Jonathan P. Stoye, “Proviral protein (2003): 13013–13018. Freely accessible provides placental function,” Proceedings of (2011) at http://www.pnas.org/con- the National Academy of Sciences USA 106 tent/100/22/13013.full.pdf+html (2009): 11827–11828. Freely accessible 108. Cécile Esnault, Stéphane Priet, David (2011) at http://www.pnas.org/con- Ribet, Cécile Vernochet, Thomas Bruls, tent/106/29/11827.full.pdf+html Christian Lavialle, Jean Weissenbach & 113. Sarah Prudhomme, Guy Oriol & Fran- Thierry Heidmann, “A placenta-specific çois Mallet, “A Retroviral Promoter and receptor for the fusogenic, endogenous a Cellular Enhancer Define a Bipartite retrovirus-derived, human syncytin-2,” Element which Controls env ERVWE1 Proceedings of the National Academy of Placental Expression,” Journal of Virology Sciences USA 105 (2008): 17532–17537. 78 (2004): 12157–12168. Freely acces- Freely accessible (2011) at http://www. sible (2011) at http://jvi.asm.org/cgi/ pnas.org/content/105/45/17532.full. reprint/78/22/12157 pdf+html 114. You-Hong Cheng, Brian D. Richardson, 109. Anne Dupressoir, Geoffroy Marceau, Michael A. Hubert & Stuart Handwerger, Cécile Vernochet, Laurence Bénit, Colette “Isolation and Characterization of the Kanellopoulos, Vincent Sapin & Thierry Human Syncytin Gene Promoter,” Biol- Heidmann, “Syncytin-A and syncytin-B, ogy of Reproduction 70 (2004): 694–701. two fusogenic placenta-specific murine en- Freely accessible (2011) at http://www. velope genes of retroviral origin conserved biolreprod.org/content/70/3/694.full. in Muridae,” Proceedings of the National pdf+html Academy of Sciences USA 102 (2005): 725– 115. François Mallet, Olivier Bouton, Sarah 730. Freely accessible (2011) at http:// Prudhomme, Valérie Cheynet, Guy Oriol, www.pnas.org/content/102/3/725.full. Bertrand Bonnaud, Gérard Lucotte, Lau- pdf+html rent Duret & Bernard Mandrand, “The 110. Anne Dupressoir, Cécile Vernochet, Ol- endogenous retroviral locus ERVWE-1 ivia Bawa, Francis Harper, Gérard Pierron, is a bona fide gene involved in hominoid Paule Opolon & Thierry Heidmann, “Syn- placental physiology,” Proceedings of the cytin-A knockout mice demonstrate the National Academy of Sciences USA 101 critical role in placentation of a fusogenic, (2004): 1731–1736. Freely accessible endogenous retrovirus-derived, envelope (2011) at http://www.pnas.org/con- gene,” Proceedings of the National Academy tent/101/6/1731.full.pdf+html of Sciences USA 106 (2009): 12127–12132. 116. James A. Shapiro & Richard von Stern- Freely accessible (2011) at http://www. berg, “Why repetitive DNA is essential pnas.org/content/106/29/12127.full. to genome function,” Biological Reviews pdf+html 80 (2005): 227–250. Freely accessible 111. Odile Heidmann, Cécile Vernochet, (2011) at http://shapiro.bsd.uchicago.edu/ Anne Dupressoir & Thierry Heidmann, Shapiro&Sternberg.2005.BiolRevs.pdf “Identification of an endogenous retroviral 117. Francis S. Collins, The Language of God: envelope gene with fusogenic activity and A Scientist Presents Evidence for Belief (New placenta-specific expression in the rabbit: York: Free Press, 2006), pp. 136–137. a new ‘syncytin’ in a third order of mammals,” Retrovirology 6 (2009): 107. Freely 7. Functions Independent accessible (2011) at http://www.retrovi- of Exact Sequence rology.com/content/6/1/107 1. David Gubb, “Intron-Delay and the Pre- cision of Expression of Homeotic Gene 143 / Notes 7. Functions Independent of Exact Sequence

Products in Drosophila,” Developmental 3p21.3,” DNA Research 6 (1999): 227–233. Genetics 7 (1986): 119–131. Freely accessible (2011) at http://dnare- 2. Carl S. Thummel, “Mechanisms of Tran- search.oxfordjournals.org/cgi/reprint/6 scriptional Timing in Drosophila,” Science /4/227?view=long&pmid=10492169 255 (1992): 39–40. 8. Roel van Driel, Paul F. Fransz & Pernette 3. Ian A. Swinburne & Pamela A. Silver, J. Verschure, “The eukaryotic genome: a “Intron Delays and Transcriptional Tim- system regulated at different hierarchi- ing during Development,” Developmental cal levels,” Journal of Cell Science 116 Cell 14 (2008): 324–330. Freely accessible (2003): 4067–4075. Freely accessible (2011) at http://www.ncbi.nlm.nih.gov/ (2011) at http://jcs.biologists.org/cgi/ pmc/articles/PMC2825037/pdf/ni- reprint/116/20/4067 hms176861.pdf 9. Tom Misteli, “Beyond the sequence: cellu- 4. Jennifer C. Chow, Constance Ciaudo, lar organization of genome function,” Cell Melissa J. Fazzari. Nathan Mise, Nicolas 128 (2007): 787–800. Servant, Jacob L. Glass, Matthew Attreed, 10. Emile Zuckerkandl, “Junk DNA and sec- Philip Avner, Anton Wutz, Emmanuel torial gene repression,” Gene 205 (1997): Barillot, John M. Greally, Olivier Voin- 323–343. net & Edith Heard, “LINE-1 activity in 11. Emile Zuckerkandl, “Why so many non- facultative heterochromatin formation coding nucleotides? The eukaryote genome during X chromosome inactivation,” Cell as an epigenetic machine,” Genetica 115 141 (2010): 956–969. (2002): 105–129. 5. Ann L. Boyle, S. Gwyn Ballard & David 12. Emile Zuckerkandl & Giacomo Cavalli, C. Ward, “Differential distribution of long “Combinatorial epigenetics, ‘junk DNA’, and short interspersed element sequences and the evolution of complex organisms,” in the mouse genome: chromosome karyo- Gene 390 (2007): 232–242. typing by fluorescence in situ hybridiza- 13. Michael Bulger & Mark Groudine, tion,” Proceedings of the National Academy “Looping versus linking: toward a model 87 (1990): 7757–7761. of Sciences USA for long-distance gene activation,” Genes & Freely accessible (2011) at http://www. Development 13 (1999): 2465–2477. Freely pnas.org/content/87/19/7757.full. accessible (2011) at http://genesdev.cshlp. pdf+html org/content/13/19/2465.full.pdf+html 6. J. M. Craig & W. A. Bickmore, “Chromo- 14. Gong Hong Wei, De Pei Liu & Chih some bands—flavours to savour,”BioEssays Chuan Liang, “Chromatin domain bound- 15 (1993): 349–354. aries: insulators and beyond,” Cell Research 7. Yataro Daigo, Minoru Isomura, Tadashi 15 (2005): 292–300. Freely accessible Nishiwaki, Kazufumi Suzuki, Osamu (2011) at http://www.nature.com/cr/ Maruyama, Kumiko Takeuchi, Yuka journal/v15/n4/pdf/7290298a.pdf Yamane, Rie Hayashi, Maiko Minami, 15. Susan E. Celniker & Robert A. Drewell, Yoshiaki Hojo, Ikuo Uchiyama, Toshihisa “Chromatin looping mediates boundary Takagi & Yusuke Nakamura, “Significant element promoter interactions,” BioEssays Differences in the Frequency of Tran- 29 (2007): 7–10. scriptional Units, Types and Numbers of 16. Peter Fraser, “Transcriptional control Repetitive Elements, GC Content, and thrown for a loop,” the Number of CpG Islands Between a Current Opinion in Ge- 16 (2006): 490–495. 1010-kb G-band Genomic Segment on netics & Development Chromosome 9q31.3 and a 1200-kb R- 17. Robert-Jan T. S. Palstra, “Close encoun- band Genomic Segment on Chromosome ters of the 3C kind: long-range chromatin 144 / Notes 7. Functions Independent of Exact Sequence

interactions and transcriptional regula- 23. Stephen C. J. Parker, Loren Hansen, tion,” Briefings in Functional Genomics and Hatice Ozel Abaan, Thomas D. Tullius & Proteomics 8 (2009): 297–309. Elliott H. Margulies, “Local DNA Topog- 18. Anita Göndör & Rolf Ohlsson, “Chro- raphy Correlates with Functional Non- mosome crosstalk in three dimensions,” coding Regions of the Human Genome,” Nature 461 (2009): 212–217. Science 324 (2009): 389–392. 19. John L. Rinn, Michael Kertesz, Jordon K. 24. Antonio Rodríguez-Campos & Fer- Wang, Sharon L. Squazzo, Xiao Xu, Sa- nando Azorín, “RNA Is an Integral Com- mantha A. Brugmann, Henry Goodnough, ponent of Chromatin that Contributes to Jill A. Helms, Peggy J. Farnham, Eran Its Structural Organization,” PLoS One Segal & Howard Y. Chang, “Functional 2:11 (2007): e1182. Freely accessible (2011) Demarcation of Active and Silent Chro- at http://www.plosone.org/article/ matin Domains in Human HOX Loci info%3Adoi%2F10.1371%2Fjournal. by Noncoding RNAs,” Cell 129 (2007): pone.0001182 1311–1323. Freely accessible (2011) at 25. Helder Maiato, Jennifer DeLuca, E. D. http://www.ncbi.nlm.nih.gov/pmc/ar- Salmon & William C. Earnshaw, “The dy- ticles/PMC2084369/pdf/nihms26949. namic kinetochore-microtubule interface,” pdf Journal of Cell Science 117 (2004): 5461– 20. Miao-Chih Tsai, Ohad Manor, Yue Wan, 5477. Freely accessible (2011) at http://jcs. Nima Mosammaparast, Jordon K. Wang, biologists.org/cgi/reprint/117/23/5461 Fei Lan, Yang Shi, Eran Segal & Howard 26. Xingkun Liu, Ian McLeod, Scott An- Y. Chang, “Long Noncoding RNA as derson, John R. Yates III & Xiangwei He, Modular Scaffold of Histone Modification “Molecular analysis of kinetochore archi- Complexes,” Science 329 (2010): 689–693. tecture in fission yeast,”EMBO Journal Freely accessible (2011) at http://www.ncbi. 24 (2005): 2919–2930. Freely accessible nlm.nih.gov/pmc/articles/PMC2967777/ (2011) at http://www.nature.com/em- pdf/nihms244741.pdf boj/journal/v24/n16/pdf/7600762a.pdf 21. Michaela Angermayr, Ulrich Oechsner, 27. Ajit P. Joglekar, David C. Bouck, Jeffrey Kerstin Gregor, Gary P. Schroth & Wolf- N. Molk, Kerry S. Bloom & Edward hard Bandlow, “Transcription initiation D. Salmon, “Molecular architecture in vivo without classical transactivators: of a kinetochore-microtubule attach- DNA kinks flanking the core promoter of ment site,” Nature Cell Biology 8 (2006): the housekeeping yeast adenylate kinase 581–585. Freely accessible (2011) at http:// gene, AKY2, position nucleosomes and www.ncbi.nlm.nih.gov/pmc/articles/ constitutively activate transcription,” Nu- PMC2867088/pdf/nihms199890.pdf cleic Acids Research 30 (2002): 4199–4207. 28. Iain M. Cheeseman & Arshad Desai, Freely accessible (2011) at http://nar.ox- “Molecular architecture of the kinetochore– fordjournals.org/content/30/19/4199.full. microtubule interface,” Nature Reviews pdf+html Molecular Cell Biology 9 (2008): 33–46. 22. Jason A. Greenbaum, Bo Pang & Thom- 29. Xiaohu Wan, Ryan P. O’Quinn, Heather as D. Tullius “Construction of a genome- L. Pierce, Ajit P. Joglekar, Walt E. Gall, scale structural map at single-nucleotide Jennifer G. DeLuca, Christopher W. Car- resolution,” Genome Research 17 (2007): roll, Song-Tao Liu, Tim J. Yen, Bruce F. 947–953. Freely accessible (2011) at http:// McEwen, P. Todd Stukenberg, Arshad genome.cshlp.org/content/17/6/947.full. Desai & Edward D. Salmon, “Protein pdf+html Architecture of the Human Kinetochore Microtubule Attachment Site,” Cell 145 / Notes 7. Functions Independent of Exact Sequence

137 (2009): 672–684. Freely accessible (2011) at http://jcb.rupress.org/con- (2011) at http://www.ncbi.nlm.nih.gov/ tent/179/3/411.full.pdf+html pmc/articles/PMC2699050/pdf/ni- 37. Rachel J. O’Neill & Dawn M. Carone, hms114285.pdf “The role of ncRNA in centromeres: a les- 30. Ajit P. Joglekar, Kerry S. Bloom & son from marsupials,” Progress in Molecular Edward D. Salmon, “In vivo protein ar- and Subcellular Biology 48 (2009): 77–101. chitecture of the eukaryotic kinetochore 38. Thomas A. Volpe, Catherine Kidner, Ira with nanometer scale accuracy,” Current M. Hall, Grace Teng, Shiv I. S. Grewal Biology 19 (2009): 694–699. Freely acces- & Robert A. Martienssen, “Regulation of sible (2011) at http://www.ncbi.nlm.nih. Heterochromatic Silencing and Histone gov/pmc/articles/PMC2832475/pdf/ H3 Lysine-9 Methylation by RNAi,” Sci- nihms178290.pdf ence 297 (2002): 1833–1837. Available 31. Katheleen Gardiner, “Clonability and online with registration (2011) at http:// gene distribution on human chromosome www.sciencemag.org/cgi/content/ 21: reflections of junk DNA content?” full/297/5588/1833 Gene 205 (1997): 39–46. 39. Christopher N. Topp, Cathy X. Zhong 32. James W. Gaubatz & Richard G. Cutler, & R. Kelly Dawe, “Centromere-encoded “Mouse Satellite DNA Is Transcribed in RNAs are integral components of the Senescent Cardiac Muscle,” Journal of Bio- maize kinetochore,” Proceedings of the logical Chemistry 265 (1990): 17753–17758. National Academy of Sciences USA 101 Freely accessible (2011) at http://www.jbc. (2004): 15986–15991. Freely accessible org/content/265/29/17753.long (2011) at http://www.pnas.org/con- 33. F. Rudert, S. Bronner, J. M. Garnier & P. tent/101/45/15986.full.pdf+html Dollé, “Transcripts from opposite strands 40. Haniaa Bouzinba-Segard, Adeline of gamma satellite DNA are differentially Guais & Claire Francastel, “Accumula- expressed during mouse development,” tion of small murine minor satellite Mammalian Genome 6 (1995): 76–83. transcripts leads to impaired centromeric 34. Brenda J. Reinhart & David P. Bartel, architecture and function,” Proceedings “Small RNAs Correspond to Centromere of the National Academy of Sciences USA Heterochromatic Repeats,” Science 297 103 (2006): 8709–8714. Freely accessible (2002): 1831. Available online with regis- (2011) at http://www.pnas.org/con- tration (2011) at http://www.sciencemag. tent/103/23/8709.full.pdf+html org/cgi/content/full/297/5588/1831 41. Federica Ferri, Haniaa Bouzinba-Segard, 35. Bruce P. May, Zachary B. Lippman, Guillaume Velasco, Florent Hubé & Yuda Fang, David L. Spector & Robert Claire Francastel, “Non-coding murine A. Martienssen, “Differential Regula- centromeric transcripts associate with and tion of Strand-Specific Transcripts from potentiate Aurora B kinase,” Nucleic Acids Arabidopsis Centromeric Satellite Repeats,” Research 37 (2009): 5071–5080. Freely ac- PLoS Genetics 1:6 (2005): e79. Freely acces- cessible (2011) at http://nar.oxfordjourn- sible (2011) at http://www.ncbi.nlm.nih. als.org/cgi/reprint/37/15/5071 gov/pmc/articles/PMC1317654/pdf/ 42. Lee H. Wong, Kate H. Brettingham- pgen.0010079.pdf Moore, Lyn Chan, Julie M. Quach, Me- 36. Junjie Lu & David M. Gilbert, “Prolif- lissa A. Anderson, Emma L. Northrop, eration-dependent and cell cycle regu- Ross Hannan, Richard Saffery, Margaret lated transcription of mouse pericentric L. Shaw, Evan Williams & K. H. Andy heterochromatin,” Journal of Cell Biology Choo, “Centromere RNA is a key compo- 179 (2007): 411–412. Freely accessible nent for the assembly of nucleoproteins at 146 / Notes 7. Functions Independent of Exact Sequence

the nucleolus and centromere,” Genome 49. Angeline Eymery, Mary Callanan & Research 17 (2007): 1146–1160. Freely Claire Vourc’h, “The secret message of het- accessible (2011) at http://genome.cshlp. erochromatin: new insights into the mech- org/content/17/8/1146.full.pdf+html anisms and function of centromeric and 43. Shiv I. S. Grewal & Sarah C. R. Elgin, pericentric repeat sequence transcription,” “Transcription and RNA interference in International Journal of Developmental Biol- the formation of heterochromatin,” Nature ogy 53 (2009): 259–268. Freely accessible 447 (2007): 399–406. (2011) at http://www.ijdb.ehu.es/web/ 44. Tom Volpe, Vera Schramke, Geor- paper.php?doi=10.1387/ijdb.082673ae gina L. Hamilton, Sharon A. White, 50. Jonathan C. Lamb & James A. Birchler, Grace Teng, Robert A. Martienssen & “The role of DNA sequence in centromere Robin C. Allshire, “RNA interference is formation,” Genome Biology 4:5 (2003): required for normal centromere function 214. Freely accessible (2011) at http:// in fission yeast,”Chromosome Research 11 genomebiology.com/content/pdf/gb- (2003): 137–146. 2003-4-5-214.pdf 45. André Verdel, Songtao Jia, Scott 51. Mary G. Schueler & Beth A. Sullivan, Gerber, Tomoyasu Sugiyama, Steven “Structural and functional dynamics of Gygi, Shiv I. S. Grewal & Danesh human centromeric chromatin,” Annual Moazed, “RNAi-Mediated Targeting of Review of Genomics and Human Genetics 7 Heterochromatin by the RITS Complex,” (2006): 301–313. Science 303 (2004): 672–676. Available 52. Beth A. Sullivan, Michael D. Blower & online with registration (2011) at http:// Gary H. Karpen, “Determining centro- www.sciencemag.org/cgi/content/ mere identity: cyclical stories and forking full/303/5658/672 paths,” Nature Reviews Genetics 2 (2001): 46. Mohammad R. Motamedi, André 584–596. Verdel, Serafin U. Colmenares, Scott A. 53. John J. Harrington, Gil Van Bokkelen, Gerber, Steven P. Gygi & Danesh Moazed, Robert W. Mays, Karen Gustashaw “Two RNAi complexes, RITS and RDRC, & Huntington F. Willard, “Formation of physically interact and localize to noncod- de novo centromeres and construction of ing centromeric RNAs,” Cell 119 (2004): first-generation human artificial micro- 789–802. chromosomes,” Nature Genetics 15 (1997): 47. Hiroaki Kato, Derek B. Goto, Robert 345–355. A. Martienssen, Takeshi Urano, Koichi 54. Desirée du Sart, Michael R. Cancilla, Furukawa & Yota Murakami, “RNA Elizabeth Earle, Jen-i Mao, Richard Saf- Polymerase II Is Required for RNAi- fery, Kellie M. Tainton, Paul Kalitsis, John Dependent Heterochromatin Assembly,” Martyn, Alyssa E. Barry & K. H. Andy Science 309 (2005): 467–469. Available Choo, “A functional neo-centromere online with registration (2011) at http:// formed through activation of a latent www.sciencemag.org/cgi/content/ human centromere and consisting of non- full/309/5733/467 alpha-satellite DNA,” Nature Genetics 16 48. Pavel Neumann, Huihuang Yan & Jim- (1997): 144–153. ing Jiang, “The Centromeric Retrotrans- 55. Peter E. Warburton, “Chromosomal posons of Rice Are Transcribed and dynamics of human neocentromere forma- Differentially Processed by RNA Interfer- tion,” Chromosome Research 12 (2004): ence,” Genetics 176 (2007): 749–761. Freely 617–626. accessible (2011) at http://www.genetics. 56. W. C. Earnshaw & N. Rothfield, “Iden- org/cgi/reprint/176/2/749 tification of a family of human centromere 147 / Notes 7. Functions Independent of Exact Sequence

proteins using autoimmune sera from (2011) at http://www.pnas.org/con- patients with scleroderma,” Chromosoma tent/104/12/5008.full.pdf+html 91 (1985): 313–321. 62. Mònica Torras-Llort, Olga Moreno- 57. Douglas K. Palmer, Kathleen O’Day, Moreno & Fernando Azorín, “Focus on Mark H. Wener, Brian S. Andrews & the centre: the role of chromatin on the Robert L. Margolis, “A 17-kD Centro- regulation of centromere identity and mere Protein (CENP-A) Copurifies function,” EMBO Journal 28 (2009): with Nucleosome Core Particles and 2337–2348. Freely accessible (2011) at with Histones,” Journal of Cell Biology http://www.ncbi.nlm.nih.gov/pmc/ 104 (1987): 805–815. Freely accessible articles/PMC2722248/pdf/embo- (2011) at http://jcb.rupress.org/con- j2009174a.pdf tent/104/4/805.long 63. Aaron A. Van Hooser, Ilia I. Ouspenski, 58. Peter E. Warburton, Carol A. Cooke, Heather C. Gregson, Daniel A. Starr, Sylvie Bourassa, Omid Vafa, Beth A. Tim J. Yen, Michael L. Goldberg, Kyoko Sullivan, Gail Stetten, Giorgio Gimelli, Yokomori, William C. Earnshaw, Kevin F. Dorothy Warburton, Chris Tyler-Smith, Sullivan & B. R. Brinkley, “Specification Kevin F. Sullivan, Guy G. Poirier & Wil- of kinetochore-forming chromatin by the liam C. Earnshaw, “Immunolocalization of histone H3 variant CENP-A,” Journal of CENP-A suggests a distinct nucleosome Cell Science 114 (2001): 3529–3542. Freely structure at the inner kinetochore plate accessible (2011) at http://jcs.biologists. of active centromeres,” Current Biology 7 org/cgi/reprint/114/19/3529 (1997): 901–904. 64. Larissa J. Vos, Jakub K. Famulski & 59. Aaron A. Van Hooser, Michael A. Man- Gordon K.T. Chan, “How to build a cini, C. David Allis, Kevin F. Sullivan & B. centromere: from centromeric and peri- R. Brinkley, “The mammalian centromere: centromeric chromatin to kinetochore structural domains and the attenuation of assembly,” Biochemistry and Cell Biology 84 chromatin modeling,” FASEB Journal 13 (2006): 619–639. Freely accessible (2011) Supplement (1999): S216-S220. Freely ac- at http://article.pubs.nrc-cnrc.gc.ca/ppv/ cessible (2011) at http://www.fasebj.org/ RPViewDoc?issn=0829-8211&volume cgi/reprint/13/9002/S216 =84&issue=4&startPage=619 60. Kinya Yoda, Satoshi Ando, Setsuo 65. Deborah L. Grady, Robert L. Ratliff, Morishita, Kenichi Houmura, Keiji Donna L. Robinson, Erin C. McCanlies, Hashimoto, Kunio Takeyasu & Tuneko Julianne Meyne & Robert K. Moyzis, Okazaki, “Human centromere protein “Highly conserved repetitive DNA se- A (CENP-A) can replace histone H3 in quences are present at human centromeres,” nucleosome reconstitution in vitro,” Pro- Proceedings of the National Academy of Sci- ceedings of the National Academy of Sciences ences USA 89 (1992): 1695–1699. Freely USA 97 (2000): 7266–7271. Freely ac- accessible (2011) at http://www.pnas.org/ cessible (2011) at http://www.pnas.org/ content/89/5/1695.full.pdf+html content/97/13/7266.full.pdf+html 66. Jiming Jiang, Shuhei Nasuda, Fenggao 61. Ben E. Black, Melissa A. Brock, Sabrina Dong, Christopher W. Sherrer, Sung-Sick Bédard, Virgil L. Woods, Jr. & Don W. Woo, Rod A. Wing, Bikram S. Gill & Cleveland, “An epigenetic mark generated David C. Ward, “A conserved repetitive by the incorporation of CENP-A into DNA element located in the centromeres centromeric nucleosomes,” Proceedings of cereal chromosomes,” Proceedings of of the National Academy of Sciences USA the National Academy of Sciences USA 93 104 (2007): 5008–5013. Freely accessible (1996): 14210–14213. Freely accessible 148 / Notes 7. Functions Independent of Exact Sequence

(2011) at http://www.pnas.org/con- 73. Gregory P. Copenhaver, Kathryn Nickel, tent/93/24/14210.full.pdf+html Takashi Kuromori, Maria-Ines Benito, 67. Huntington F. Willard, “Chromosome- Samir Kaul, Xiaoying Lin, Michael Bevan, Specific Organization of Human Alpha George Murphy, Barbara Harris, Lau- Satellite DNA,” American Journal of Hu- rence D. Parnell, W. Richard McCombie, man Genetics 37 (1985): 524–532. Freely Robert A. Martienssen, Marco Marra & accessible (2011) at http://www.ncbi.nlm. Daphne Preuss, “Genetic Definition and nih.gov/pmc/articles/PMC1684601/ Sequence Analysis of Arabidopsis Centro- pdf/ajhg00158-0092.pdf meres,” Science 286 (1999): 2468–2474. 68. John S. Waye & Huntington F. Wil- Available online with registration (2011) at lard, “Chromosome-specific alpha satellite http://www.sciencemag.org/cgi/content/ DNA: nucleotide sequence analysis of the full/286/5449/2468 2.0 kilobasepair repeat from the human 74. Wolfgang Haupt, Thilo C. Fischer, Sa- X chromosome,” Nucleic Acids Research bine Winderl, Paul Fransz & Ramón A. 13 (1985): 2731–2743. Freely accessible Torres-Ruiz, “The centromere1 (CEN1) (2011) at http://www.ncbi.nlm.nih. region of Arabidopsis thaliana: architecture gov/pmc/articles/PMC341190/pdf/ and functional impact of chromatin,” The nar00302-0062.pdf Plant Journal 27 (2001): 285–296. 69. R. Heller, K. E. Brown, C. Burgtorf & 75. Sarah E. Hall, Gregory Kettler & Daph- W. R. A. Brown, “Mini-chromosomes ne Preuss, “Centromere Satellites from derived from the human Y chromosome by Arabidopsis Populations: Maintenance of telomere directed chromosome breakage,” Conserved and Variable Domains,” Ge- Proceedings of the National Academy of Sci- nome Research 13 (2003): 195–205. Freely ences USA 93 (1996): 7125–7130. Freely accessible (2011) at http://genome.cshlp. accessible (2011) at http://www.pnas.org/ org/content/13/2/195.full.pdf+html content/93/14/7125.full.pdf+html 76. Anthony W. I. Lo, Jeffrey M. Craig, 70. Terence D. Murphy and Gary H. Richard Saffery, Paul Kalitsis, Danielle Karpen, “Centromeres Take Flight: Alpha V. Irvine, Elizabeth Earle, Dianna J. Satellite and the Quest for the Human Magliano & K. H. Andy Choo, “A 330 kb Centromere,” Cell 93 (1998): 317–320. CENP-A binding domain and altered rep- 71. Brenda R. Grimes, Angela A. Rhoades lication timing at a human neocentromere,” & Huntington F. Willard, “Alpha-satellite EMBO Journal 20 (2001): 2087–2096. DNA and vector composition influence Freely accessible (2011) at http://www. rates of human artificial chromosome nature.com/emboj/journal/v20/n8/ pdf/7593708a.pdf formation,” Molecular Therapy 5 (2002): 798–805. 77. Anderly C. Chueh, Lee H. Wong, Nicho- 72. M. Katharine Rudd, Robert W. Mays, las Wong & K.H. Andy Choo, “Variable Stuart Schwartz & Huntington F. Wil- and hierarchical size distribution of L1- lard, “Human Artificial Chromosomes retroelement-enriched CENP-A clusters with Alpha Satellite-Based De Novo within a functional human neocentromere,” Centromeres Show Increased Fre- Human Molecular Genetics 14 (2005): 85– quency of Nondisjunction and Anaphase 93. Freely accessible (2011) at http://hmg. oxfordjournals.org/cgi/reprint/14/1/85 Lag,” Molecular and Cellular Biology 23 (2003): 7689–7697. Freely accessible 78. Anderly C. Chueh, Emma L. Northrop, (2011) at http://mcb.asm.org/cgi/re- Kate H. Brettingham-Moore, K. H. print/23/21/7689 Andy Choo & Lee H. Wong, “LINE Retrotransposon RNA Is an Essential 149 / Notes 7. Functions Independent of Exact Sequence

Structural and Functional Epigenetic mosome 6 and its response to interferon in Component of a Core Neocentromeric interphase nuclei,” Journal of Cell Science Chromatin,” PLoS Genetics 5:1 (2009): 113 (2000): 1565–1576. Freely accessible e1000354. Freely accessible (2011) at (2011) at http://jcs.biologists.org/cgi/ http://www.plosgenetics.org/article/ reprint/113/9/1565 info%3Adoi%2F10.1371%2Fjournal. 84. Li-Feng Zhang, Khanh D. Huynh & pgen.1000354 Jeannie T. Lee, “Perinucleolar targeting of 79. Stephen M. Stack, David B. Brown the inactive X during S phase: evidence for & William C. Dewey, “Visualization of a role in the maintenance of silencing,” Cell interphase chromosomes,” Journal of Cell 129 (2007): 693–706. Science 26 (1977): 281–299. Limited access 85. Christian Lanctôt, Thierry Cheutin, (2011) at http://jcs.biologists.org/cgi/ Marion Cremer, Giacomo Cavalli & reprint/26/1/281 Thomas Cremer, “Dynamic genome ar- 80. Jenny A. Croft, Joanna M. Bridger, Shel- chitecture in the nuclear space: regulation agh Boyle, Paul Perry, Peter Teague & of gene expression in three dimensions,” Wendy A. Bickmore, “Differences in the Nature Reviews Genetics 8 (2007): 104–115. Localization and Morphology of Chromo- 86. Boris Joffe, Heinrich Leonhardt & Irina somes in the Human Nucleus,” Journal of Solovei, “Differentiation and large scale Cell Biology 145 (1999): 1119–1131. Freely spatial organization of the genome,” Cur- accessible (2011) at http://jcb.rupress. rent Opinion in Genetics and Development org/content/145/6/1119.full.pdf+html 20 (2010): 562–569. 81. Heiner Albiez, Marion Cremer, Cinzia 87. M. R. Hübner & D. L. Spector, “Chro- Tiberi, Lorella Vecchio, Lothar Scher- matin dynamics,” Annual Review of Bio- melleh, Sandra Dittrich, Katrin Küpper, physics 39 (2010): 471–489. Boris Joffe, Tobias Thormeyer, Johann von 88. Hideki Tanizawa, Osamu Iwasaki, Hase, Siwei Yang, Karl Rohr, Heinrich Atsunari Tanaka, Joseph R. Capizzi, Leonhardt, Irina Solovei, Christoph Cre- Priyankara Wickramasinghe, Mihee Lee, mer, Stanislav Fakan & Thomas Cremer, Zhiyan Fu & Ken-ichi Noma, “Mapping “Chromatin domains and the interchroma- of long-range associations throughout tin compartment form structurally defined the fission yeast genome reveals global and functionally interacting nuclear net- genome organization linked to transcrip- works,” 14 (2006): Chromosome Research tional regulation,” Nucleic Acids Research 707–733. 38 (2010): 8164–8177. Freely accessible 82. Thomas Cremer & Marion Cremer, (2011) at http://nar.oxfordjournals.org/ “Chromosome Territories,” Cold Spring content/38/22/8164.long Harbor Perspectives in Biology 2 (2010): 89. Luis A. Parada, Philip G. McQueen a003889. Freely accessible (2011) at http:// & Tom Misteli, “Tissue-specific spatial cshperspectives.cshlp.org/content/2/3/ organization of genomes,” Genome Biology a003889.full.pdf+html 5:7 (2004): R44. Freely accessible (2011) at 83. Emanuela V. Volpi, Edith Chevret, Tania http://genomebiology.com/content/pdf/ Jones, Radost Vatcheva, Jill Williamson, gb-2004-5-7-r44.pdf Stephan Beck, R. Duncan Campbell, 90. Tom Sexton, Heiko Schober, Peter Fra- Michelle Goldsworthy, Stephen H. Powis, ser & Susan M. Gasser, “Gene regulation Jiannis Ragoussis, John Trowsdale & De- through nuclear organization,” Nature nise Sheer, “Large-scale chromatin orga- Structural & Molecular Biology 14 (2007): nization of the major histocompatibility 1049–1055. complex and other regions of human chro- 150 / Notes 7. Functions Independent of Exact Sequence

91. Takumi Takizawa, Karen J. Mea- 98. Davide Marenduzzo, Cristian Micheletti burn & Tom Misteli, “The meaning of & Peter R. Cook, “Entropy-Driven Ge- gene positioning,” Cell 135 (2008): 9–13. nome Organization,” Biophysical Journal 92. Erik D. Andrulis, Aaron M. Neiman, 90 (2006): 3712–3721. Freely accessible David C. Zappulla & Rolf Sternglanz, (2011) at http://www.ncbi.nlm.nih.gov/ “Perinuclear localization of chromatin fa- pmc/articles/PMC1440752/pdf/3712.pdf cilitates transcriptional silencing,” Nature 99. Peter R. Cook & Davide Marenduzzo, 394 (1998): 592–595. “Entropic organization of interphase 93. Shelagh Boyle, Susan Gilchrist, Joanna chromosomes,” Journal of Cell Biology M. Bridger, Nicola L. Mahy, Juliet A. Ellis 186 (2009): 825–834. Freely accessible & Wendy A. Bickmore, “The spatial orga- (2011) at http://jcb.rupress.org/con- nization of human chromosomes within tent/186/6/825.full.pdf+html the nuclei of normal and emerin-mutant 100. Jan Postberg, Olga Alexandrova, Thom- cells,” Human Molecular Genetics 10 as Cremer & Hans J. Lipps, “Exploiting (2001): 211–219. Freely accessible (2011) nuclear duality of ciliates to analyse topo- at http://hmg.oxfordjournals.org/con- logical requirements for DNA replication tent/10/3/211.full.pdf+html and transcription,” Journal of Cell Science 94. Lars Guelen, Ludo Pagie, Emilie Bras- 118 (2005): 3973–3983. Freely accessible set, Wouter Meuleman, Marius B. Faza, (2011) at http://jcs.biologists.org/cgi/ Wendy Talhout, Bert H. Eussen, Annelies reprint/118/17/3973 de Klein, Lodewyk Wessels, Wouter de 101. L. D. Carter-Dawson & M. M. LaVail, Laat & Bas van Steensel, “Domain orga- “Rods and cones in the mouse retina. I. nization of human chromosomes revealed Structural analysis using light and electron by mapping of nuclear lamina interactions,” microscopy,” Journal of Comparative Neu- Nature 453 (2008): 948–951. rology 188 (1979): 245–262. 95. Lee E. Finlan, Duncan Sproul, Inga 102. Seth Blackshaw, Rebecca E. Fraio- Thomson, Shelagh Boyle, Elizabeth li, Takahisa Furukawa & Constance L. Kerr, Paul Perry, Bauke Ylstra, Jonathan Cepko, “Comprehensive analysis of pho- R. Chubb & Wendy A. Bickmore, “Re- toreceptor gene expression and the identi- cruitment to the Nuclear Periphery fication of candidate retinal disease genes,” Can Alter Expression of Genes in Hu- Cell 107 (2001): 579–589. man Cells,” PLoS Genetics 4:3 (2008): 103. Dominique Helmlinger, Sara Hardy, e1000039. Freely accessible (2011) at Gretta Abou-Sleymane, Adrien Eberlin, http://www.plosgenetics.org/article/ Aaron B. Bowman, Anne Gansmüller, info%3Adoi%2F10.1371%2Fjournal. Serge Picaud, Huda Y. Zoghbi, Yvon pgen.1000039 Trottier, Làszlò Tora & Didier Devys, 96. K. L. Reddy, J. M. Zullo, E. Bertolino “Glutamine-Expanded Ataxin-7 Alters & H. Singh, “Transcriptional repression TFTC/STAGA Recruitment and mediated by repositioning of genes to Chromatin Structure Leading to Pho- the nuclear lamina,” Nature 452 (2008): toreceptor Dysfunction,” PLoS Biology 243–247. 4:3 (2006): e67. Freely accessible (2011) 97. Myriam Ruault, Marion Dubarry & at http://www.plosbiology.org/article/ Angela Taddei, “Re-positioning genes to info%3Adoi%2F10.1371%2Fjournal. the nuclear envelope in mammalian cells: pbio.0040067 impact on transcription,” Trends in Genet- 104. Irina Solovei, Moritz Kreysing, Chris- ics 24 (2008): 574–581. tian Lanctôt, Süleyman Kösem, Leo Peichl, Thomas Cremer, Jochen Guck & 151 / Notes 8. Some Recent Defenders of Junk DNA

Boris Joffe, “Nuclear Architecture of Rod 3. Todd A. Gray, Alison Wilson, Patrick J. Photoreceptor Cells Adapts to Vision in Fortin & Robert D. Nicholls, “The puta- Mammalian Evolution,” Cell 137 (2009): tively functional Mkrn1-p1 pseudogene is 356–368. neither expressed nor imprinted, nor does 105. Irina Solovei, Moritz Kreysing, Chris- it regulate its source gene in trans,” Proceed- tian Lanctôt, Süleyman Kösem, Leo ings of the National Academy of Sciences Peichl, Thomas Cremer, Jochen Guck USA 103 (2006): 12039–12044. Freely & Boris Joffe, “Nuclear Architecture accessible (2011) at http://www.pnas.org/ of Rod Photoreceptor Cells Adapts to content/103/32/12039.full.pdf+html Vision in Mammalian Evolution,” Cell 4. José Manuel Franco-Zorrilla, Adrián Valli, 137 (2009): Supplementary Data. Freely Marco Todesco, Isabel Mateos, María accessible (2011) at http://download. Isabel Puga, Ignacio Rubio-Somoza, An- cell.com/mmcs/journals/0092-8674/ tonio Leyva, Detlef Weigel, Juan Antonio PIIS0092867409001378.mmc1.pdf García & Javier Paz-Ares, “Target mimicry 106. Caroline Kizilyaprak, Danièle Speh- provides a new mechanism for regulation ner, Didier Devys & Patrick Schultz, “In of microRNA activity,” Nature Genetics 39 Vivo Chromatin Organization of Mouse (2007): 1033–1037. Rod Photoreceptors Correlates with 5. Laura Poliseno, Leonardo Salmena, Ji- Histone Modifications,”PLoS One 5:6 angwen Zhang, Brett Carver, William (2010): e11039. Freely accessible (2011) J. Haveman & Pier Paolo Pandolfi, “A at http://www.plosone.org/article/ coding-independent function of gene and info%3Adoi%2F10.1371%2Fjournal. pseudogene mRNAs regulates tumour pone.0011039 biology,” Nature 465 (2010): 1033–1038. 107. Moritz Kreysing, Lars Boyde, Jochen 6. Kayoko Yamada, Jun Lim, Joseph M. Guck & Kevin J. Chalut, “Physical insight Dale, Huaming Chen, Paul Shinn, Curtis into light scattering by photoreceptor J. Palm, Audrey M. Southwick, Hank C. cell nuclei,” Optics Letters 35 (2010): Wu, Christopher Kim, Michelle Nguyen, 2639–2641. Paul Pham, Rosa Cheuk, George Karlin- Newmann, Shirley X. Liu, Bao Lam, Hi- 8. Some Recent Defenders tomi Sakano, Troy Wu, Guixia Yu, Molly of Junk DNA Miranda, Hong L. Quach, Matthew Tripp, 1. Shinji Hirotsune, Noriyuki Yoshida, Amy Charlie H. Chang, Jeong M. Lee, Mitsue Chen, Lisa Garrett, Fumihiro Sugiyama, Toriumi, Marie M. H. Chan, Carolyn Satoru Takahashi, Ken-ichi Yagami, An- C. Tang, Courtney S. Onodera, Justine thony Wynshaw-Boris & Atsushi Yoshiki, M. Deng, Kenji Akiyama, Yasser Ansari, “An expressed pseudogene regulates the Takahiro Arakawa, Jenny Banh, Fumika messenger-RNA stability of its homolo- Banno, Leah Bowser, Shelise Brooks, gous coding gene,” Nature 423 (2003): Piero Carninci, Qimin Chao, Nathan 91–96. Choy, Akiko Enju, Andrew D. Goldsmith, 2. William S. Harris & John H. Cal- Mani Gurjal, Nancy F. Hansen, Yoshihide vert, “Intelligent Design: The Scientific Hayashizaki, Chanda Johnson-Hopson, Alternative to Evolution,” The National Vickie W. Hsuan, Kei Iida, Meagan Catholic Bioethics Quarterly (August 2003): Karnes, Shehnaz Khan, Eric Koesema, 531–561. Freely accessible (2011) at http:// Junko Ishida, Paul X. Jiang, Ted Jones, Jun www.intelligentdesignnetwork.org/ Kawai, Asako Kamiya, Cristina Meyers, NCBQ3_3HarrisCalvert.pdf Maiko Nakajima, Mari Narusaka, Motoa- ki Seki, Tetsuya Sakurai, Masakazu Satou, Racquel Tamse, Maria Vaysberg, Erika 152 / Notes 8. Some Recent Defenders of Junk DNA

K. Wallender, Cecilia Wong, Yuki Yama- (May 19, 2010). Freely accessible (2011) mura, Shiaulou Yuan, Kazuo Shinozaki, at http://blogs.discovermagazine.com/ Ronald W. Davis, Athanasios Theologis loom/2010/05/19/how-many-sparks-in- & Joseph R. Ecker, “Empirical Analysis of the-genome/ Transcriptional Activity in the Arabidopsis 14. RepeatMasker, Institute for Systems Biol- Genome,” Science 302 (2003): 842–846. ogy. Freely accessible (2011) at http://www. Available online with registration (2011) repeatmasker.org/ at http://www.sciencemag.org/cgi/con- 15. Jill Cheng, Philipp Kapranov, Jorg tent/full/302/5646/842 Drenkow, Sujit Dike, Shane Brubaker, 7. Jason M. Johnson, Stephen Edwards, Dan- Sandeep Patel, Jeffrey Long, David Stern, iel Shoemaker & Eric E. Schadt, “Dark Hari Tammana, Gregg Helt, Victor Se- matter in the genome: evidence of wide- mentchenko, Antonio Piccolboni, Stefan spread transcription detected by microar- Bekiranov, Dione K. Bailey, Madhavan ray tiling experiments,” Trends in Genetics Ganesh, Srinka Ghosh, Ian Bell, Daniela 21 (2005): 93–102. S. Gerhard & Thomas R. Gingeras, “Tran- 8. Guy Riddihough, “In the Forests of RNA scriptional Maps of 10 Human Chromo- Dark Matter,” Science 309 (2005): 1507. somes at 5-Nucleotide Resolution,” Science 9. Harm van Bakel & Timothy R. Hughes, 308 (2005): 1149–1154. “Establishing legitimacy and function in the 16. P. Z. Myers, “Junk DNA is still junk,” new transcriptome,” Briefings in Functional The Panda’s Thumb (May 19, 2010). Freely Genomics & Proteomics 8 (2009): 424–436. accessible (2011) at http://pandasthumb. 10. Harm van Bakel, Corey Nislow, org/archives/2010/05/junk-dna-is-sti. Benjamin J. Blencowe & Timothy R. html Hughes, “Most ‘Dark Matter’ Tran- 17. Philipp Kapranov, Georges St. Laurent, scripts Are Associated With Known Tal Raz, Fatih Ozsolak, C. Patrick Reyn- Genes,” PLoS Biology 8:5 (2010): olds, Poul H. B. Sorensen, Gregory Rea- e1000371. Freely accessible (2011) at man, Patrice Milos, Robert J. Arceci, John http://www.plosbiology.org/article/ F. Thompson & Timothy J. Triche, “The info%3Adoi%2F10.1371%2Fjournal. majority of total nuclear-encoded non- pbio.1000371 ribosomal RNA in a human cell is ‘dark 11. The ENCODE Project Consortium, matter’ un-annotated RNA,” BMC Biology “Identification and analysis of functional 8:1 (2010): 149. Freely accessible (2011) at elements in 1% of the human genome http://www.biomedcentral.com/1741- by the ENCODE pilot project,” Nature 7007/8/149 447 (2007): 799–816. Freely accessible 18. Mark Blaxter, “Revealing the Dark Mat- (2011) at http://www.ncbi.nlm.nih.gov/ ter of the Genome,” Science 330 (2010): pmc/articles/PMC2212820/pdf/ni- 1758–1759. hms27513.pdf 19. Philipp Kapranov, Aarron T. Willing- 12. Richard Robinson, “Dark Matter ham & Thomas R. Gingeras, “Genome- Transcripts: Sound and Fury, Signify- wide transcription and the implications ing Nothing?” PLoS Biology 8:5 (2010): for genomic organization,” Nature Reviews e1000370. Freely accessible (2011) at Genetics 8 (2007): 413–423. http://www.plosbiology.org/article/ 20. John L. Rinn, Michael Kertesz, Jordon K. info%3Adoi%2F10.1371%2Fjournal. Wang, Sharon L. Squazzo, Xiao Xu, Sa- pbio.1000370 mantha A. Brugmann, Henry Goodnough, 13. Carl Zimmer, “How Many Sparks in the Jill A. Helms, Peggy J. Farnham, Eran Genome?” Discover Magazine: The Loom Segal, and Howard Y. Chang, “Functional 153 / Notes 8. Some Recent Defenders of Junk DNA

Demarcation of Active and Silent Chro- 30. Daniel L. Hartl, “Molecular melodies in matin Domains in Human HOX Loci high and low C,” Nature Reviews Genetics 1 by Non-Coding RNAs,” Cell 129 (2007): (2000): 145–149. 1311–1323. Freely accessible (2011) at 31. Thomas Cavalier-Smith, “Nuclear http://www.ncbi.nlm.nih.gov/pmc/ar- volume control by nucleoskeletal DNA, ticles/PMC2084369/?tool=pubmed selection for cell volume and cell growth 21. Elizabeth Pennisi, “Shining a Light on rate, and the solution of the DNA C-value the Genome’s ‘Dark Matter’,” Science 330 paradox,” Journal of Cell Science 34 (1978): (2010): 1614. 247–278. Freely accessible (2011) at http:// 22. T. Ryan Gregory, “Junk DNA: let me say jcs.biologists.org/cgi/reprint/34/1/247 it one more time,” Genomicron (Septem- 32. Thomas Cavalier-Smith, “Cell Volume ber 16, 2007). Freely accessible (2011) at and the Evolution of Eukaryotic Genome http://www.genomicron.evolverzone. Size,” pp. 105–184 in Thomas Cavalier- com/2007/09/junk-dna-let-me-say-it- Smith (editor), The Evolution of Genome one-more-time/ Size (Chichester, UK: John Wiley & Sons, 23. T. Ryan Gregory, “The onion test,”Geno- 1985). micron (April 25, 2007). Freely accessible 33. Alexander E. Vinogradov, “Nucleotypic (2011) at http://www.genomicron.evolv- Effect in Homeotherms: Body-Mass-Cor- erzone.com/2007/04/onion-test/ rected Basal Metabolic Rate of Mammals 24. Roger Vendrely & Colette Vendrely, Is Related to Genome Size,” Evolution 49 “La teneur du noyau cellulaire en acide (1995): 1249–1259. désoxyribonucléique à travers les organes, 34. R. A. Van Den Bussche, J. L. Longmire les individus et les espèces animales: Tech- & R. J. Baker, “How bats achieve a small niques et premiers resultants,” Experientia C-value: frequency of repetitive DNA in 4 (1948): 434–436. Macrotus,” Mammalian Genome 6 (1995): 25. A. E. Mirsky & Hans Ris, “The Desoxy- 521–525. ribonucleic Acid Content of Animal Cells 35. Austin L. Hughes & Marianne K. and Its Evolutionary Significance,”Journal Hughes, “Small genomes for better flyers,” of General Physiology 34 (1951): 451–462. Nature 377 (1995): 391. Freely accessible (2011) at http:// 36. Alexander E. Vinogradov, “Nucleotypic www.ncbi.nlm.nih.gov/pmc/articles/ Effect in Homeotherms: Body-Mass In- PMC2147229/pdf/451.pdf dependent Resting Metabolic Rate of Pas- 26. C. A. Thomas, Jr., “The Genetic Organi- serine Birds Is Related to Genome Size,” zation of Chromosomes,” Annual Review of Evolution 51 (1997): 220–225. Genetics 5 (1971): 237–256. 37. T. Ryan Gregory, “A bird’s-eye view of the 27. Joseph G. Gall, “Chromosome Structure C-value enigma: genome size, cell size, and and the C-Value Paradox,” Journal of Cell metabolic rate in the class aves,” Evolution Biology 91 (1981): 3s-14s. Freely acces- 56 (2002): 121–130. sible (2011) at http://jcb.rupress.org/ 38. Stanley K. Sessions & Allan Larson, content/91/3/3s.full.pdf “Developmental Correlates of Genome Size 28. Gordon P. Moore, “The C-Value Para- in Plethodontid Salamanders and their dox,” BioScience 34 (July/August 1984): Implications for Genome Evolution,” Evo- 425–429. lution 41 (1987): 1239–1251. 29. Wen-Hsiung Li, Molecular Evolution 39. T. Ryan Gregory & Paul D. N. Hebert, (Sunderland, MA: Sinauer Associates, “The Modulation of DNA Content: Proxi- 1997), pp. 379–384. mate Causes and Ultimate Consequences,” Genome Research 9 (1999): 317–324. Freely 154 / Notes 9. A Summary of the Case for Functionality in Junk DNA

accessible (2011) at http://genome.cshlp. of the Cambridge Philosophical Society 76 org/content/9/4/317.full.pdf+html (2001): 65–101. 40. T. Ryan Gregory, “Genome size and 50. T. Ryan Gregory, “Genome Size Evolu- developmental complexity,” Genetica 115 tion in Animals,” pp. 3–87 in T. Ryan (2002): 131–146. Gregory (editor), The Evolution of the 41. T. Ryan Gregory, “The C-value Enigma Genome (Amsterdam: Elsevier, 2005), pp. in Plants and Animals: A Review of Paral- 48–49. lels and an Appeal for Partnership,” Annals 51. T. Ryan Gregory, “An opportunity for of Botany 95 (2005): 133–146. Freely ac- ID to be scientific,” Genomicron (July cessible (2011) at http://aob.oxfordjourn- 10, 2007). Freely accessible (2011) at als.org/content/95/1/133.full.pdf+html http://www.genomicron.evolverzone. 42. T. Ryan Gregory & J. S. Johnston, “Ge- com/2007/07/opportunity-for-id-to-be- nome size diversity in the family Drosophi- scientific/ lidae,” Heredity 101 (2008): 228–238. 52. William A. Dembski, Intelligent Design: 43. Emile Zuckerkandl, “Gene control in The Bridge Between Science and Theology eukaryotes and the c-value paradox ‘excess’ (Downer’s Grove, IL: InterVarsity Press, DNA as an impediment to transcription 2002), p. 150. of coding sequences,” Journal of Molecular 53. William A. Dembski, The Design Revolu- Evolution 9 (1976): 73–104. tion (Downer’s Grove, IL: InterVarsity 44. Sean Luke, “Evolutionary computation Press, 2004), p. 272. and the c-value paradox,” Proceedings of the 54. T. Ryan Gregory, “Function, non- 2005 conference on Genetic and Evolutionary function, some function: a brief history of Computation (2005): 91–97. junk DNA,” Genomicron (June 14, 2007). 45. Thomas Cavalier-Smith, “Economy, Freely accessible (2011) at http://www. speed and size matter: evolutionary forces genomicron.evolverzone.com/2007/06/ driving nuclear genome miniaturization function-non-function-some-function/ and expansion,” Annals of Botany 95 (2005): 147–175. 9. A Summary of the Case for 46. Ryan J. Taft, Michael Pheasant & John S. Functionality in Junk DNA Mattick, “The relationship between non- 1. Luis M. Mendes Soares & Juan Valcárcel, protein-coding DNA and eukaryotic com- “The expanding transcriptome: the genome as the ‘Book of Sand’,” plexity,” BioEssays 29 (2007): 288–299. EMBO Journal 25 (2006): 923–931. Available online 47. L. I. Patrushev & I. G. Minkevich, “The with registration (2011) at http://www. Problem of the Eukaryotic Genome Size,” nature.com/emboj/journal/v25/n5/ Biochemistry (Moscow) 73 (2008): 1519– full/7601023a.html 1552. Freely accessible (2011) at http:// 2. Piero Carninci, Jun Yasuda & Yoshihide protein.bio.msu.ru/biokhimiya/contents/ v73/full/73131519.html Hayashizaki,“Multifaceted mammalian transcriptome,” Current Opinion in Cell 48. Eduard Kejnovsky, Ilia J. Leitch & An- Biology 20 (2008): 274–280. drew R. Leitch, “Contrasting evolutionary dynamics between angiosperm and mam- 3. Yoseph Barash, John A. Calarco, Weijun Gao, Qun Pan, Xinchen Wang, Ofer Shai, malian genomes,” Trends in Ecology and Benjamin J. Blencowe & Brendan J. Frey, Evolution 24 (2009): 572–582. “Deciphering the splicing code,” Nature 465 49. T. Ryan Gregory, “Coincidence, coevolu- (2010): 53–59. tion, or causation? DNA content, cell size, 4. Laura Poliseno, Leonardo Salmena, Ji- and the C-value enigma,” Biological Reviews angwen Zhang, Brett Carver, William 155 / Notes 10. From Junk DNA to a New Understanding of the Genome

J. Haveman & Pier Paolo Pandolfi, “A Transcripts Are Associated With coding-independent function of gene and Known Genes,” PLoS Biology 8 (2010): pseudogene mRNAs regulates tumour e1000371. Freely accessible (2011) at biology,” Nature 465 (2010): 1033–1038. http://www.plosbiology.org/article/ 5. Ryan D. Walters, Jennifer F. Kugel & info%3Adoi%2F10.1371%2Fjournal. James A. Goodrich, “InvAluable junk: the pbio.1000371 cellular impact and function of Alu and B2 13. P. Z. Myers, “Junk DNA is still junk,” RNAs,” IUBMB Life 61 (2009): 831–837. The Panda’s Thumb (May 19, 2010). Freely 6. Victoria V. Lunyak, Gratien G. Pre- accessible (2011) at http://pandasthumb. fontaine, Esperanza Núñez, Thorsten org/archives/2010/05/junk-dna-is-sti. Cramer, Bong-Gun Ju, Kenneth A. Ohgi, html Kasey Hutt, Rosa Roy, Angel García-Díaz, 14. Philipp Kapranov, Georges St. Laurent, Xiaoyan Zhu, Yun Yung, Lluís Monto- Tal Raz, Fatih Ozsolak, C. Patrick Reyn- liu, Christopher K. Glass & Michael G. olds, Poul H. B. Sorensen, Gregory Rea- Rosenfeld, “Developmentally regulated man, Patrice Milos, Robert J. Arceci, John activation of a SINE B2 repeat as a do- F. Thompson & Timothy J. Triche, “The main boundary in organogenesis,” Science majority of total nuclear-encoded non- 317 (2007): 248–251. ribosomal RNA in a human cell is ‘dark 7. Jonathan P. Stoye, “Proviral protein pro- matter’ un-annotated RNA,” BMC Biology vides placental function,” Proceedings of 8:1 (2010): 149. Freely accessible (2011) at the National Academy of Sciences USA 106 http://www.biomedcentral.com/1741- (2009): 11827–11828. Freely accessible 7007/8/149 (2011) at http://www.pnas.org/content/106/29/11827.full.pdf+html 10. From Junk DNA to a New 8. Emile Zuckerkandl, “Why so many non- Understanding of the Genome coding nucleotides? The eukaryote genome 1. Francis S. Collins, The Language of God: A (New as an epigenetic machine,” Genetica 115 Scientist Presents Evidence for Belief (2002): 105–129. York: Free Press, 2006), p. 136. 9. Stephen C. J. Parker, Loren Hansen, 2. John C. Avise, Inside the Human Genome: Hatice Ozel Abaan, Thomas D. Tullius & A Case for Non-Intelligent Design (Oxford: Elliott H. Margulies, “Local DNA Topog- Oxford University Press, 2010), p. 115. raphy Correlates with Functional Non- 3. Douglas J. Futuyma, Evolution (Sunder- coding Regions of the Human Genome,” land, MA: Sinauer Associates, 2005), p. Science 324 (2009): 389–392. 456. 10. T. Ryan Gregory, “Junk DNA: let me say 4. PubMed. Freely accessible (2011) at it one more time,” Genomicron (Septem- http://www.ncbi.nlm.nih.gov/sites/ ber 16, 2007). Freely accessible (2011) at pubmed http://www.genomicron.evolverzone. 5. James A. Shapiro & Richard von Stern- com/2007/09/junk-dna-let-me-say-it- berg, “Why repetitive DNA is essential to one-more-time/ genome function,” Biological Reviews 80 11. T. Ryan Gregory, “The onion test,”Geno- (2005): 227–250. Freely accessible (2011) micron (April 25, 2007). Freely accessible at http://shapiro.bsd.uchicago.edu/ (2011) at http://www.genomicron.evolv- Shapiro&Sternberg.2005.BiolRevs.pdf erzone.com/2007/04/onion-test/ 6. The ENCODE Project Consortium, 12. Harm van Bakel, Corey Nislow, “Identification and analysis of functional Benjamin J. Blencowe & Timothy elements in 1% of the human genome R. Hughes, “Most ‘Dark Matter’ by the ENCODE pilot project,” Nature 156 / Notes 10. From Junk DNA to a New Understanding of the Genome

447 (2007): 799–816. Freely accessible creationism/general/analysis-discovery- (2011) at http://www.ncbi.nlm.nih.gov/ institutes-bibliography pmc/articles/PMC2212820/pdf/ni- 17. NCSE Staff, “Analysis of the Discovery hms27513.pdf Institute’s Bibliography: Appendix,” Na- 7. Geoff Spencer & Anna-Lynn Wegener, tional Center for Science Education (June 1, “New Findings Challenge Established 2002). Freely accessible (2011) at http:// Views on Human Genome,” NIH News ncse.com/creationism/general/analysis- (June 13, 2007). Freely accessible (2011) at discovery-institutes-bibliography- http://genome.gov/25521554 appendix 8. Catherine Shaffer, “One Scientist’s Junk Is 18. Center for Science & Culture Staff, a Creationist’s Treasure,” Wired Magazine “Questions and Answers About the Discov- Blog (June 13, 2007). Freely accessible ery Institute’s Bibliography of Supplemen- (2011) at http://www.wired.com/science/ tary Resources for Ohio Science Instruc- discoveries/news/2007/06/junk_dna tion,” Discovery Institute (April 15, 2002). 9. Francis S. Collins, The Language of Life: Freely accessible (2011) at http://www. DNA and the Revolution in Personalized arn.org/docs2/news/discoveryresponse- Medicine (New York: HarperCollins, toncse041702.htm 2010), pp. 5–6, 9–10. 19. Charles Darwin, The Origin of Species by 10. Collins, The Language of Life, p. 293. Means of Natural Selection (London: John Murray, 1859 p. 459. Freely accessible 11. Francis S. Collins, The Language of God: , (2011) at http://darwin-online.org.uk/ A Scientist Presents Evidence for Belief (New York: Free Press, 2006), pp. 199–203. content/frameset?viewtype=side&itemI D=F373&pageseq=477 12. “About the BioLogos Foundation,” Bi- oLogos. Freely accessible (2011) at http:// 20. Darwin, The Origin of Species,p. 437. biologos.org/about Freely accessible (2011) at http://darwin- online.org.uk/content/frameset?viewtyp 13. Darrel Falk, “A Rejoinder to Part II of e=side&itemID=F373&pageseq=455 Stephen C. Meyer’s Response to Francisco Ayala,” BioLogos Forum (March 11, 2010). 21. Jonathan Wells, “Darwin’s Straw God Freely accessible (2011) at http://biologos. Argument,” Journal of Interdisciplinary org/blog/a-rejoinder-to-meyer-2 Studies 22 (2010): 67–88. An earlier version (December 31, 2008) is freely ac- 14. Karl Giberson, “Does Intelligent Design cessible (2011) at http://www.discovery. Really Explain a Complex and Puzzling org/a/8101 World?” BioLogos Forum (March 15, 2010). Freely accessible (2011) at http:// 22. Neal C. Gillespie, Charles Darwin and the biologos.org/blog/does-intelligent-design- Problem of Creation (Chicago: The Univer- really-explain-a-complex-and puzzling- sity of Chicago Press, 1979), pp. 124–125, world/ 146. 15. Center for Science & Culture Staff, “Bib- 23. Cornelius G. Hunter, Darwin’s God liography of Supplementary Resources for (Grand Rapids, MI: Brazos Press, 2001), pp. 48–49, 84, 158. Science Instruction,” Discovery Institute (March 11, 2002). Freely accessible (2011) 24. Paul A. Nelson, “The role of theology in at http://www.discovery.org/a/1127 current evolutionary reasoning,” Biology 16. NCSE Staff, “Analysis of the Discovery and Philosophy 11 (1996): 493 – 517. Institute’s Bibliography,” National Center 25. Gregory Radick, “Deviance, Darwinina- for Science Education (June 1, 2002). Freely Style,” Metascience (2005) 14:453–457. accessible (2011) at http://ncse.com/ Freely accessible (2011) at http://www. 157 / Notes 10. From Junk DNA to a New Understanding of the Genome

personal.leeds.ac.uk/~phlgmr/Greg%20 36. Hubert P. Yockey, Information Theory Articles/Deviance.pdf and Molecular Biology (Cambridge: Cam- 26. Abigail J. Lustig, “Natural Atheology,” bridge University Press, 1992). pp. 69–83 in Abigail J. Lustig, Robert J. 37. William A. Dembski, The Design Infer- Richards & Michael Ruse (editors), Dar- ence (Cambridge: Cambridge University winian Heresies (Cambridge: Cambridge Press, 1998). University Press: 2004). 38. Wen-Yu Chung, Samir Wadhawan, 27. Elliott Sober, Evidence and Evolution Radek Szklarczyk, Sergei Kosakovsky (Cambridge: Cambridge University Press, Pond & Anton Nekrutenko, “A first 2008), pp. 126–128. look at ARFome: dual-coding genes 28. Steven R. Scadding, “Vestigial organs in mammalian genomes,” PLoS Com- do not provide scientific evidence for putational Biology 3:5 (2007): e91. evolution,” Evolutionary Theory 6 (1982): Freely Accessible (2011) at http:// 171–173. www.ploscompbiol.org/article/ 29. Jonathan Wells, “Darwin of the Gaps: info%3Adoi%2F10.1371%2Fjournal. Francis Collins’s Premature Surrender,” pp. pcbi.0030091 117–128 in Jay W. Richards (editor), God 39. Shalev Itzkovitz & Uri Alon, “The genet- and Evolution (Seattle, WA: Discovery ic code is nearly optimal for allowing ad- Institute Press, 2010). An earlier version ditional information within protein-coding (March 26, 2008) is freely accessible (2011) sequences,” Genome Research 17 (2007): at http://www.discovery.org/a/4529 405–412. Freely accessible (2011) at http:// 30. Miller, “Life’s Grand Design” (1994). genome.cshlp.org/content/17/4/405.full. Freely accessible (2011) at http://www. pdf+html millerandlevine.com/km/evol/lgd/ 40. Tobias Bollenbach, Kalin Vetsigian & index.html Roy Kishony, “Evolution and multilevel optimization of the genetic code,” 31. Bill Gates, The Road Ahead (New York: Genome Penguin Books, 1995), p. 188. Research 17 (2007): 401–404. Freely accessible (2011) at http://genome.cshlp.org/ 32. Stephen C. Meyer, “The origin of biologi- content/17/4/401.full.pdf+html cal information and the higher taxonomic 41. Dembski, , pp. 317. categories,” Proceedings of the Biological The Design Revolution Society of Washington 117 (2004): 213–239. 42. Danielle S. Bassett, Daniel L. Greenfield, Freely accessible (2011) at http://www. Andreas Meyer-Lindenberg, Daniel R. discovery.org/a/2177 Weinberger, Simon W. Moore & Edward T. Bullmore, “Efficient physical embedding 33. Stephen C. Meyer, Signature in the Cell: of topologically complex information pro- DNA and the Evidence for Intelligent Design (New York: HarperCollins, 2009). More cessing networks in brains and computer information available online (2011) at circuits,” PLoS Computational Biology 6:4 http://www.discovery.org/a/12311 (2010): e1000748. Freely accessible (2011) at http://www.ploscompbiol.org/article/ 34. William A. Dembski, The Design Revo- info%3Adoi%2F10.1371%2Fjournal. lution: Answering the Toughest Questions pcbi.1000748 about Intelligent Design (Downer’s Grove, IL: InterVarsity Press, 2004), pp. 317. 43. Richard v. Sternberg, “On the Roles of Repetitive DNA Elements in the Context 35. Leon Brillouin, Science and Information of a Unified Genomic–Epigenetic System,” Theory, Second Edition (New York: Aca- Annals of the New York Academy of Sciences demic Press, 1956). 981 (2002): 154–188. 158 / Notes Appendix. The Vitamin C Pseudogene

44. Richard v. Sternberg, “DNA Codes in Fish,” Annals of the New York Academy and Information: Formal Structures and of Sciences 258 (1975): 81–102. Relational Causes,” Acta Biotheoretica 56 9. Régis Moreau & Konrad Dabrowski, (2008): 205–232. “Gulonolactone oxidase presence in fishes: 45. Richard v. Sternberg & James A. Shap- activity and significance,” pp. 14–32 in iro, “How repeated retroelements format Konrad Dabrowski (editor), Ascorbic Acid genome function,” Cytogenetic and Genome in Aquatic Organisms (Boca Raton, LA: Research 110 (2005): 108–116. CRC Press, 2001). 10. Morimitsu Nishikimi & Kunio Yagi, Appendix. The Vitamin “Molecular basis for the deficiency in C Pseudogene humans of gulonolactone oxidase, a key 1. Juan M. Navia & Charles E. Hunt, “Nutri- enzyme for ascorbic acid biosynthesis,” tion, Nutritional Diseases, and Nutrition American Journal of Clinical Nutrition 54 Research Applications,” pp. 235–267 in (1991): 1203S-1208S. Freely accessible Joseph E. Wagner & Patrick J. Manning (2011) at http://www.ajcn.org/cgi/ (editors), The Biology of the Guinea Pig reprint/54/6/1203S (New York: Academic Press, 1976). 11. Morimitsu Nishikimi, Ryuichi Fuku- 2. Yasuo Nakajima, Totada R. Shantha yama, Sinsei Minoshima, Nobuyoshi & Geoffrey H. Bourne, “Histochemical Shimizu & Kunio Yagi, “Cloning and detection of L-gulonolactone: phenazine Chromosomal Mapping of the Human methosulfate oxidoreductase activity in Nonfunctional Gene for L-Gulono- several mammals with special reference to gamma-lactone Oxidase, the Enzyme for synthesis of vitamin C in primates,” Histo- L-Ascorbic Acid Biosynthesis Missing chemie 18 (1969): 293–301. in Man,” Journal of Biological Chemistry 3. R. N. Roy & B. C. Guha, “Species Dif- 269 (1994): 13685–13688. Freely acces- ferences in regard to the Biosynthesis sible (2011) at http://www.jbc.org/con- of Ascorbic Acid,” Nature 182 (1958): tent/269/18/13685.long 319–320. 12. Kenneth R. Miller, Only a Theory: Evolu- 4. Elmer C. Birney, Robert Jenness & Kath- tion and the Battle for America’s Soul (New leen M. Ayaz, “Inability of bats to synthe- York: Viking, 2008), p. 98. sise L-ascorbic acid,” Nature 260 (1976): 13. Miller, Only a Theory, p. 99. 626–628. 14. Jonathan Wells, “Should We Stop Criti- 5. Jie Cui, Yi-Hsuan Pan, Yijian Zhang, Ga- cizing the Doctrine of Universal Common reth Jones & Shuyi Zhang, “Progressive Ancestry?” Access Research Network (No- Pseudogenization: Vitamin C synthesis vember 3, 2001). Freely accessible (2011) at and Its Loss in Bats,” Molecular Biology and http://www.arn.org/docs/wells/jw_crit- Evolution (October 29, 2010). doi:10.1093/ icizingcommonancestry1103.htm molbev/msq286. 15. William A. Dembski, The Design Revo- 6. C. Ray Chaudhuri & I. B. Chatterjee, “L- lution: Answering the Toughest Questions Ascorbic Acid Synthesis in Birds: Phyloge- About Intelligent Design (Downer’s Grove, netic Trend,” Science 164 (1969): 435–436. IL: InterVarsity Press, 2004), p. 42. 7. Carlos Martínez del Rio, “Can Passerines 16. Stephen C. Meyer, “Intelligent Design vs. Synthesize Vitamin C?” The Auk 114 Evolution,” Think Tank With Ben Watten- (1997): 513–516. berg (October 12, 2006). Freely accessible 8. J. E. Halver, R. R. Smith, B. M. Tolbert & (2011) at http://www.pbs.org/think- E. M. Baker, “Utilization of Ascorbic Acid tank/transcript1244.html 159 / Notes Appendix. The Vitamin C Pseudogene

17. Paul A. Nelson, “Design and Common 25. Jerry A. Coyne, Why Evolution Is True Ancestry,” Evolution News & Views (May (New York: Viking, 2009), p. 68. 7, 2007). Freely accessible (2011) at http:// 26. Coyne, Why Evolution Is True, p. 69. www.evolutionnews.org/2007/05/_ 27. Jennifer F. Hughes, Helen Skaletsky, most_people_including.html Tatyana Pyntikova, Tina A. Graves, 18. Casey Luskin, “Wikipedia ‘Intelligent Saskia K. M. van Daalen, Patrick J. Minx, Design’ Entry Selectively Cites Poll Data Robert S. Fulton, Sean D. McGrath, to Present Misleading Picture of Support Devin P. Locke, Cynthia Friedman, Bar- for Intelligent Design,” Evolution News bara J. Trask, Elaine R. Mardis, Wesley & Views (May 8, 2007). Freely accessible C. Warren, Sjoerd Repping, Steve Rozen, (2011) at http://www.evolutionnews. Richard K. Wilson & David C. Page, org/2007/05/wikipedia_intelligent_de- “Chimpanzee and human Y chromosomes sign_e003542.html are remarkably divergent in structure and 19. Michael J. Behe, Darwin’s Black Box: The gene content,” Nature 463 (2010): 536–539. Biochemical Challenge to Evolution (New 28. Don E. Wilson & DeeAnn M. Reeder York: The Free Press, 1996), p. 231. (editors), Mammal Species of the World: A 20. W. Ford Doolittle, “The practice of clas- Taxonomic and Geographic Reference, Third sification and the theory of evolution, and Edition (Baltimore, MD: Johns Hopkins what the demise of Charles Darwin’s tree University Press, 2005). Freely accessible of life hypothesis means for both of them,” (2011) at http://www.bucknell.edu/ Philosophical Transactions of the Royal Soci- msw3/ ety of London B 364 (2009): 2221–2228. 29. Yuriko Ohta & Morimitsu Nishikimi, 21. Carl R. Woese & Nigel Goldenfeld, “Random nucleotide substitutions in “How the Microbial World Saved Evolu- primate nonfunctional gene for L-gulono- tion from the Scylla of Molecular Biology gamma-lactone oxidase, the missing and the Charybdis of the Modern Syn- enzyme in L-ascorbic acid biosynthesis,” thesis,” Microbiology and Molecular Biology Biochimica et Biophysica Acta 1472 (1999): Reviews 73 (2009): 14–21. Freely accessible 408–411. (2011) at http://mmbr.asm.org/cgi/re- 30. Yoko Inai, Yuriko Ohta & Morimitsu print/73/1/14 Nishikimi, “The whole structure of the 22. David G. Popovich & Ellen S. Dieren- human nonfunctional L-gulono-gamma- feld, “Gorilla Nutrition,” in J. Ogden & D. lactone oxidase gene—the gene responsible Wharton (editors), Management of Gorillas for scurvy—and the evolution of repetitive in Captivity (Silver Spring, MD: Ameri- sequences thereon,” Journal of Nutri- can Association of Zoos and Aquariums, tional Science and Vitaminology (Tokyo) 49 1997). Freely accessible (2011) at http:// (2003): 315–319. www.nagonline.net/HUSBANDRY/ 31. Evgeniy S. Balakirev & Francisco J. Ayala, Diets%20pdf/Gorilla%20Nutrition.pdf “Pseudogenes: Are They ‘Junk’ or Func- 23. Committee on Animal Nutrition, Nutri- tional DNA?” Annual Review of Genetics ent Requirements of Nonhuman Primates, 37 (2003): 123–51. Second Revised Edition (Washington, 32. Amit N. Khachane & Paul M. Har- DC: National Academies Press, 2003), pp. rison, “Assessing the genomic evidence for 137–149. conserved transcribed pseudogenes under 24. Gorilla (Gorilla gorilla). Ensembl (Cam- selection,” BMC Genomics 10 (2009): 435. bridge). Freely accessible (2011) at http:// Freely accessible (2011) at http://www. uswest.ensembl.org/Gorilla_gorilla/ biomedcentral.com/1471-2164/10/435 Info/Index