The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome

Laurence D. Hurst, Avazeh T. Ghanbarian, Alistair R R Forrest, Lukasz Huminiecki, Michael Rehli, J. Kenneth Baillie, Michiel J L de Hoon, Vanja Haberle, Timo Lassmann, Ivan V. Kulakovskiy, Marina Lizio, Masayoshi Itoh, Robin Andersson, Christopher J. Mungall, Terrence F. Meehan, Sebastian Schmeier, Nicolas Bertin, Mette Jørgensen, Emmanuel Dimont, Erik Arner & 243 others Christian Schmidl, Ulf Schaefer, Yulia A. Medvedeva, Charles Plessy, Morana Vitezic, Jessica Severin, Colin A. Semple, Yuri Ishizu, Robert S. Young, Margherita Francescatto, Intikhab Alam, Davide Albanese, Gabriel M. Altschuler, Takahiro Arakawa, John A C Archer, Peter Arner, Magda Babina, Sarah Baker, Piotr J. Balwierz, Anthony G. Beckhouse, Swati Bhatt Pradhan, Judith A. Blake, Antje Blumenthal, Beatrice Bodega, Alessandro Bonetti, James Briggs, Frank Brombacher, A. Maxwell Burroughs, Andrea Califano, Carlo V. Cannistraci, Daniel Carbajo, Yun Chen, Marco Chierici, Yari Ciani, Hans C. Clevers, Emiliano Dalla, Carrie A. Davis, Michael Detmar, Alexander D. Diehl, Taeko Dohi, Finn Drabløs, Albert S B Edge, Matthias Edinger, Karl Ekwall, Mitsuhiro Endoh, Hideki Enomoto, Michela Fagiolini, Lynsey Fairbairn, Hai Fang, Mary C. Farach-Carson, Geoffrey J. Faulkner, Alexander V. Favorov, Malcolm E. Fisher, Martin C. Frith, Rie Fujita, Shiro Fukuda, Cesare Furlanello, Masaaki Furuno, Jun ichi Furusawa, Teunis B. Geijtenbeek, Andrew Gibson, Thomas Gingeras, Daniel Goldowitz, Julian Gough, Sven Guhl, Reto Guler, Stefano Gustincich, Thomas J. Ha, Masahide Hamaguchi, Mitsuko Hara, Matthias Harbers, Jayson Harshbarger, Akira Hasegawa, Yuki Hasegawa, Takehiro Hashimoto, Meenhard Herlyn, Kelly J. Hitchens, Shannan J. Ho Sui, Oliver M. Hofmann, Ilka Hoof, Fumi Hori, Lukasz Huminiecki, Kei Iida, Tomokatsu Ikawa, Boris R. Jankovic, Hui Jia, Anagha Joshi, Giuseppe Jurman, Bogumil Kaczkowski, Chieko Kai, Kaoru Kaida, Ai Kaiho, Kazuhiro Kajiyama, Mutsumi Katayama Kanamori, Artem S. Kasianov, Takeya Kasukawa, Shintaro Katayama, Sachi Kato, Shuji Kawaguchi, Hiroshi Kawamoto, Yuki I. Kawamura, Tsugumi Kawashima, Judith S. Kempfle, Tony J. Kenna, Juha Kere, Levon M. Khachigian, Toshio Kitamura, S. Peter Klinken, Alan J. Knox, Miki Kojima, Soichi Kojima, Naoto Kondo, Haruhiko Koseki, Shigeo Koyasu, Sarah Krampitz, Atsutaka Kubosaki, Andrew T. Kwon, Jeroen F J Laros, Weonju Lee, Andreas Lennartsson, Kang Li, Berit Lilje, Leonard Lipovich, Alan sim Mackay, Riichiroh Manabe, Jessica C. Mar, Benoit Marchand, Anthony Mathelier, Niklas Mejhert, Alison Meynert, Yosuke Mizuno, David A. de Lima Morais, Hiromasa Morikawa, Mitsuru Morimoto, Kazuyo Moro, Efthymios Motakis, Hozumi Motohashi, Christine L. Mummery, Mitsuyoshi Murata, Sayaka Sato Nagao, Yutaka Nakachi, Fumio Nakahara, Toshiyuki Nakamura, Yukio Nakamura, Kenichi Nakazato, Erik van Nimwegen, Noriko Ninomiya, Hiromi Nishiyori, Shohei Noma, Tadasuke Nozaki, Soichi Ogishima, Naganari Ohkura, Hiroko Ohmiya, Hiroshi Ohno, Mitsuhiro Ohshima, Mariko Hatakeyama Okada, Yasushi Okazaki, Valerio Orlando, Dmitry A. Ovchinnikov, Arnab Pain, Robert Passier, Margaret Patrikakis, Helena Persson, Silvano Piazza, James G D Prendergast, Owen J L Rackham, Jordan A. Ramilowski, Mamoon Rashid, Timothy Ravasi, Patrizia Rizzu, Marco Roncador, Sugata Roy, Morten B. Rye, Eri Saijyo, Antti Sajantila, Akiko Saka, Shimon Sakaguchi, Mizuho Sakai, Hiroki Sato, Hironori Satoh, Suzana Savvi, Alka Saxena, Claudio Schneider, Erik A. Schultes, Gundula G. Schulze-Tanzil, Anita Schwegmann, Thierry Sengstag, Guojun Sheng, Hisashi Shimoji, Yishai Shimoni, Jay W. Shin, Christophe Simon, Daisuke Sugiyama, Takaaki Sugiyama, Masanori Suzuki, Naoko Suzuki, Rolf K. Swoboda, Peter A C 't Hoen, Michihira Tagami, Naoko Takahashi, Jun Takai, Hiroshi Tanaka, Hideki Tatsukawa, Zuotian Tatum, Mark Thompson, Hiroo Toyoda, Tetsuro Toyoda, Eivind Valen, Marc van de Wetering, Linda M. van den Berg, Roberto Verardo, Dipti Vijayan, Ilya E. Vorontsov, Wyeth W. Wasserman, Shoko Watanabe, Christine A. Wells, Louise N. Winteringham, Ernst Wolvetang, Emily J. Wood, Yoko Yamaguchi, Masayuki Yamamoto, Misako Yoneda, Yohei Yonekura, Shigehiro Yoshida, Suzan E. Zabierowski, Peter G. Zhang, Xiaobei Zhao, Silvia Zucchelli, Kim M. Summers, Harukazu Suzuki, Carsten O. Daub, Jun Kawai, Peter Heutink, Winston Hide, Tom C. Freeman, Boris Lenhard, Vladimir B. Bajic, Martin S. Taylor, Vsevolod J. Makeev, Albin Sandelin, David A. Hume, Piero Carninci, Yoshihide Hayashizaki

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X’s gene content, gene expression, and evolution.

Original languageEnglish (US)
Article numbere1002315
JournalPLoS Biology
Volume13
Issue number12
DOIs
StatePublished - Dec 18 2015

Fingerprint

Mammalian Chromosomes
Haploidy
X Chromosome
X chromosome
Chromosomes
haploidy
Genes
autosomes
genes
X-Linked Genes
Gene Expression
Tissue
jams
Gene expression
gene expression
traffic
Encyclopedias
Pan troglodytes
Primates
Birds

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Hurst, L. D., Ghanbarian, A. T., Forrest, A. R. R., Huminiecki, L., Rehli, M., Kenneth Baillie, J., ... Hayashizaki, Y. (2015). The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome. PLoS Biology, 13(12), [e1002315]. https://doi.org/10.1371/journal.pbio.1002315

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome. / Hurst, Laurence D.; Ghanbarian, Avazeh T.; Forrest, Alistair R R; Huminiecki, Lukasz; Rehli, Michael; Kenneth Baillie, J.; de Hoon, Michiel J L; Haberle, Vanja; Lassmann, Timo; Kulakovskiy, Ivan V.; Lizio, Marina; Itoh, Masayoshi; Andersson, Robin; Mungall, Christopher J.; Meehan, Terrence F.; Schmeier, Sebastian; Bertin, Nicolas; Jørgensen, Mette; Dimont, Emmanuel; Arner, Erik; Schmidl, Christian; Schaefer, Ulf; Medvedeva, Yulia A.; Plessy, Charles; Vitezic, Morana; Severin, Jessica; Semple, Colin A.; Ishizu, Yuri; Young, Robert S.; Francescatto, Margherita; Alam, Intikhab; Albanese, Davide; Altschuler, Gabriel M.; Arakawa, Takahiro; Archer, John A C; Arner, Peter; Babina, Magda; Baker, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan, Swati Bhatt; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Maxwell Burroughs, A.; Califano, Andrea; Cannistraci, Carlo V.; Carbajo, Daniel; Chen, Yun; Chierici, Marco; Ciani, Yari; Clevers, Hans C.; Dalla, Emiliano; Davis, Carrie A.; Detmar, Michael; Diehl, Alexander D.; Dohi, Taeko; Drabløs, Finn; Edge, Albert S B; Edinger, Matthias; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey; Fang, Hai; Farach-Carson, Mary C.; Faulkner, Geoffrey J.; Favorov, Alexander V.; Fisher, Malcolm E.; Frith, Martin C.; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Jun ichi; Geijtenbeek, Teunis B.; Gibson, Andrew; Gingeras, Thomas; Goldowitz, Daniel; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J.; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard; Hitchens, Kelly J.; Ho Sui, Shannan J.; Hofmann, Oliver M.; Hoof, Ilka; Hori, Fumi; Huminiecki, Lukasz; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R.; Jia, Hui; Joshi, Anagha; Jurman, Giuseppe; Kaczkowski, Bogumil; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Kajiyama, Kazuhiro; Kanamori, Mutsumi Katayama; Kasianov, Artem S.; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawashima, Tsugumi; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Peter Klinken, S.; Knox, Alan J.; Kojima, Miki; Kojima, Soichi; Kondo, Naoto; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T.; Laros, Jeroen F J; Lee, Weonju; Lennartsson, Andreas; Li, Kang; Lilje, Berit; Lipovich, Leonard; Mackay, Alan sim; Manabe, Riichiroh; Mar, Jessica C.; Marchand, Benoit; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison; Mizuno, Yosuke; de Lima Morais, David A.; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L.; Murata, Mitsuyoshi; Nagao, Sayaka Sato; Nakachi, Yutaka; Nakahara, Fumio; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Ohmiya, Hiroko; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada, Mariko Hatakeyama; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A.; Pain, Arnab; Passier, Robert; Patrikakis, Margaret; Persson, Helena; Piazza, Silvano; Prendergast, James G D; Rackham, Owen J L; Ramilowski, Jordan A.; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Rye, Morten B.; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Schneider, Claudio; Schultes, Erik A.; Schulze-Tanzil, Gundula G.; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W.; Simon, Christophe; Sugiyama, Daisuke; Sugiyama, Takaaki; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K.; 't Hoen, Peter A C; Tagami, Michihira; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyoda, Hiroo; Toyoda, Tetsuro; Valen, Eivind; van de Wetering, Marc; van den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Vorontsov, Ilya E.; Wasserman, Wyeth W.; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise N.; Wolvetang, Ernst; Wood, Emily J.; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Suzan E.; Zhang, Peter G.; Zhao, Xiaobei; Zucchelli, Silvia; Summers, Kim M.; Suzuki, Harukazu; Daub, Carsten O.; Kawai, Jun; Heutink, Peter; Hide, Winston; Freeman, Tom C.; Lenhard, Boris; Bajic, Vladimir B.; Taylor, Martin S.; Makeev, Vsevolod J.; Sandelin, Albin; Hume, David A.; Carninci, Piero; Hayashizaki, Yoshihide.

In: PLoS Biology, Vol. 13, No. 12, e1002315, 18.12.2015.

Research output: Contribution to journalArticle

Hurst, LD, Ghanbarian, AT, Forrest, ARR, Huminiecki, L, Rehli, M, Kenneth Baillie, J, de Hoon, MJL, Haberle, V, Lassmann, T, Kulakovskiy, IV, Lizio, M, Itoh, M, Andersson, R, Mungall, CJ, Meehan, TF, Schmeier, S, Bertin, N, Jørgensen, M, Dimont, E, Arner, E, Schmidl, C, Schaefer, U, Medvedeva, YA, Plessy, C, Vitezic, M, Severin, J, Semple, CA, Ishizu, Y, Young, RS, Francescatto, M, Alam, I, Albanese, D, Altschuler, GM, Arakawa, T, Archer, JAC, Arner, P, Babina, M, Baker, S, Balwierz, PJ, Beckhouse, AG, Pradhan, SB, Blake, JA, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Maxwell Burroughs, A, Califano, A, Cannistraci, CV, Carbajo, D, Chen, Y, Chierici, M, Ciani, Y, Clevers, HC, Dalla, E, Davis, CA, Detmar, M, Diehl, AD, Dohi, T, Drabløs, F, Edge, ASB, Edinger, M, Ekwall, K, Endoh, M, Enomoto, H, Fagiolini, M, Fairbairn, L, Fang, H, Farach-Carson, MC, Faulkner, GJ, Favorov, AV, Fisher, ME, Frith, MC, Fujita, R, Fukuda, S, Furlanello, C, Furuno, M, Furusawa, JI, Geijtenbeek, TB, Gibson, A, Gingeras, T, Goldowitz, D, Gough, J, Guhl, S, Guler, R, Gustincich, S, Ha, TJ, Hamaguchi, M, Hara, M, Harbers, M, Harshbarger, J, Hasegawa, A, Hasegawa, Y, Hashimoto, T, Herlyn, M, Hitchens, KJ, Ho Sui, SJ, Hofmann, OM, Hoof, I, Hori, F, Huminiecki, L, Iida, K, Ikawa, T, Jankovic, BR, Jia, H, Joshi, A, Jurman, G, Kaczkowski, B, Kai, C, Kaida, K, Kaiho, A, Kajiyama, K, Kanamori, MK, Kasianov, AS, Kasukawa, T, Katayama, S, Kato, S, Kawaguchi, S, Kawamoto, H, Kawamura, YI, Kawashima, T, Kempfle, JS, Kenna, TJ, Kere, J, Khachigian, LM, Kitamura, T, Peter Klinken, S, Knox, AJ, Kojima, M, Kojima, S, Kondo, N, Koseki, H, Koyasu, S, Krampitz, S, Kubosaki, A, Kwon, AT, Laros, JFJ, Lee, W, Lennartsson, A, Li, K, Lilje, B, Lipovich, L, Mackay, AS, Manabe, R, Mar, JC, Marchand, B, Mathelier, A, Mejhert, N, Meynert, A, Mizuno, Y, de Lima Morais, DA, Morikawa, H, Morimoto, M, Moro, K, Motakis, E, Motohashi, H, Mummery, CL, Murata, M, Nagao, SS, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nakazato, K, van Nimwegen, E, Ninomiya, N, Nishiyori, H, Noma, S, Nozaki, T, Ogishima, S, Ohkura, N, Ohmiya, H, Ohno, H, Ohshima, M, Okada, MH, Okazaki, Y, Orlando, V, Ovchinnikov, DA, Pain, A, Passier, R, Patrikakis, M, Persson, H, Piazza, S, Prendergast, JGD, Rackham, OJL, Ramilowski, JA, Rashid, M, Ravasi, T, Rizzu, P, Roncador, M, Roy, S, Rye, MB, Saijyo, E, Sajantila, A, Saka, A, Sakaguchi, S, Sakai, M, Sato, H, Satoh, H, Savvi, S, Saxena, A, Schneider, C, Schultes, EA, Schulze-Tanzil, GG, Schwegmann, A, Sengstag, T, Sheng, G, Shimoji, H, Shimoni, Y, Shin, JW, Simon, C, Sugiyama, D, Sugiyama, T, Suzuki, M, Suzuki, N, Swoboda, RK, 't Hoen, PAC, Tagami, M, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tatum, Z, Thompson, M, Toyoda, H, Toyoda, T, Valen, E, van de Wetering, M, van den Berg, LM, Verardo, R, Vijayan, D, Vorontsov, IE, Wasserman, WW, Watanabe, S, Wells, CA, Winteringham, LN, Wolvetang, E, Wood, EJ, Yamaguchi, Y, Yamamoto, M, Yoneda, M, Yonekura, Y, Yoshida, S, Zabierowski, SE, Zhang, PG, Zhao, X, Zucchelli, S, Summers, KM, Suzuki, H, Daub, CO, Kawai, J, Heutink, P, Hide, W, Freeman, TC, Lenhard, B, Bajic, VB, Taylor, MS, Makeev, VJ, Sandelin, A, Hume, DA, Carninci, P & Hayashizaki, Y 2015, 'The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome', PLoS Biology, vol. 13, no. 12, e1002315. https://doi.org/10.1371/journal.pbio.1002315
Hurst LD, Ghanbarian AT, Forrest ARR, Huminiecki L, Rehli M, Kenneth Baillie J et al. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome. PLoS Biology. 2015 Dec 18;13(12). e1002315. https://doi.org/10.1371/journal.pbio.1002315
Hurst, Laurence D. ; Ghanbarian, Avazeh T. ; Forrest, Alistair R R ; Huminiecki, Lukasz ; Rehli, Michael ; Kenneth Baillie, J. ; de Hoon, Michiel J L ; Haberle, Vanja ; Lassmann, Timo ; Kulakovskiy, Ivan V. ; Lizio, Marina ; Itoh, Masayoshi ; Andersson, Robin ; Mungall, Christopher J. ; Meehan, Terrence F. ; Schmeier, Sebastian ; Bertin, Nicolas ; Jørgensen, Mette ; Dimont, Emmanuel ; Arner, Erik ; Schmidl, Christian ; Schaefer, Ulf ; Medvedeva, Yulia A. ; Plessy, Charles ; Vitezic, Morana ; Severin, Jessica ; Semple, Colin A. ; Ishizu, Yuri ; Young, Robert S. ; Francescatto, Margherita ; Alam, Intikhab ; Albanese, Davide ; Altschuler, Gabriel M. ; Arakawa, Takahiro ; Archer, John A C ; Arner, Peter ; Babina, Magda ; Baker, Sarah ; Balwierz, Piotr J. ; Beckhouse, Anthony G. ; Pradhan, Swati Bhatt ; Blake, Judith A. ; Blumenthal, Antje ; Bodega, Beatrice ; Bonetti, Alessandro ; Briggs, James ; Brombacher, Frank ; Maxwell Burroughs, A. ; Califano, Andrea ; Cannistraci, Carlo V. ; Carbajo, Daniel ; Chen, Yun ; Chierici, Marco ; Ciani, Yari ; Clevers, Hans C. ; Dalla, Emiliano ; Davis, Carrie A. ; Detmar, Michael ; Diehl, Alexander D. ; Dohi, Taeko ; Drabløs, Finn ; Edge, Albert S B ; Edinger, Matthias ; Ekwall, Karl ; Endoh, Mitsuhiro ; Enomoto, Hideki ; Fagiolini, Michela ; Fairbairn, Lynsey ; Fang, Hai ; Farach-Carson, Mary C. ; Faulkner, Geoffrey J. ; Favorov, Alexander V. ; Fisher, Malcolm E. ; Frith, Martin C. ; Fujita, Rie ; Fukuda, Shiro ; Furlanello, Cesare ; Furuno, Masaaki ; Furusawa, Jun ichi ; Geijtenbeek, Teunis B. ; Gibson, Andrew ; Gingeras, Thomas ; Goldowitz, Daniel ; Gough, Julian ; Guhl, Sven ; Guler, Reto ; Gustincich, Stefano ; Ha, Thomas J. ; Hamaguchi, Masahide ; Hara, Mitsuko ; Harbers, Matthias ; Harshbarger, Jayson ; Hasegawa, Akira ; Hasegawa, Yuki ; Hashimoto, Takehiro ; Herlyn, Meenhard ; Hitchens, Kelly J. ; Ho Sui, Shannan J. ; Hofmann, Oliver M. ; Hoof, Ilka ; Hori, Fumi ; Huminiecki, Lukasz ; Iida, Kei ; Ikawa, Tomokatsu ; Jankovic, Boris R. ; Jia, Hui ; Joshi, Anagha ; Jurman, Giuseppe ; Kaczkowski, Bogumil ; Kai, Chieko ; Kaida, Kaoru ; Kaiho, Ai ; Kajiyama, Kazuhiro ; Kanamori, Mutsumi Katayama ; Kasianov, Artem S. ; Kasukawa, Takeya ; Katayama, Shintaro ; Kato, Sachi ; Kawaguchi, Shuji ; Kawamoto, Hiroshi ; Kawamura, Yuki I. ; Kawashima, Tsugumi ; Kempfle, Judith S. ; Kenna, Tony J. ; Kere, Juha ; Khachigian, Levon M. ; Kitamura, Toshio ; Peter Klinken, S. ; Knox, Alan J. ; Kojima, Miki ; Kojima, Soichi ; Kondo, Naoto ; Koseki, Haruhiko ; Koyasu, Shigeo ; Krampitz, Sarah ; Kubosaki, Atsutaka ; Kwon, Andrew T. ; Laros, Jeroen F J ; Lee, Weonju ; Lennartsson, Andreas ; Li, Kang ; Lilje, Berit ; Lipovich, Leonard ; Mackay, Alan sim ; Manabe, Riichiroh ; Mar, Jessica C. ; Marchand, Benoit ; Mathelier, Anthony ; Mejhert, Niklas ; Meynert, Alison ; Mizuno, Yosuke ; de Lima Morais, David A. ; Morikawa, Hiromasa ; Morimoto, Mitsuru ; Moro, Kazuyo ; Motakis, Efthymios ; Motohashi, Hozumi ; Mummery, Christine L. ; Murata, Mitsuyoshi ; Nagao, Sayaka Sato ; Nakachi, Yutaka ; Nakahara, Fumio ; Nakamura, Toshiyuki ; Nakamura, Yukio ; Nakazato, Kenichi ; van Nimwegen, Erik ; Ninomiya, Noriko ; Nishiyori, Hiromi ; Noma, Shohei ; Nozaki, Tadasuke ; Ogishima, Soichi ; Ohkura, Naganari ; Ohmiya, Hiroko ; Ohno, Hiroshi ; Ohshima, Mitsuhiro ; Okada, Mariko Hatakeyama ; Okazaki, Yasushi ; Orlando, Valerio ; Ovchinnikov, Dmitry A. ; Pain, Arnab ; Passier, Robert ; Patrikakis, Margaret ; Persson, Helena ; Piazza, Silvano ; Prendergast, James G D ; Rackham, Owen J L ; Ramilowski, Jordan A. ; Rashid, Mamoon ; Ravasi, Timothy ; Rizzu, Patrizia ; Roncador, Marco ; Roy, Sugata ; Rye, Morten B. ; Saijyo, Eri ; Sajantila, Antti ; Saka, Akiko ; Sakaguchi, Shimon ; Sakai, Mizuho ; Sato, Hiroki ; Satoh, Hironori ; Savvi, Suzana ; Saxena, Alka ; Schneider, Claudio ; Schultes, Erik A. ; Schulze-Tanzil, Gundula G. ; Schwegmann, Anita ; Sengstag, Thierry ; Sheng, Guojun ; Shimoji, Hisashi ; Shimoni, Yishai ; Shin, Jay W. ; Simon, Christophe ; Sugiyama, Daisuke ; Sugiyama, Takaaki ; Suzuki, Masanori ; Suzuki, Naoko ; Swoboda, Rolf K. ; 't Hoen, Peter A C ; Tagami, Michihira ; Takahashi, Naoko ; Takai, Jun ; Tanaka, Hiroshi ; Tatsukawa, Hideki ; Tatum, Zuotian ; Thompson, Mark ; Toyoda, Hiroo ; Toyoda, Tetsuro ; Valen, Eivind ; van de Wetering, Marc ; van den Berg, Linda M. ; Verardo, Roberto ; Vijayan, Dipti ; Vorontsov, Ilya E. ; Wasserman, Wyeth W. ; Watanabe, Shoko ; Wells, Christine A. ; Winteringham, Louise N. ; Wolvetang, Ernst ; Wood, Emily J. ; Yamaguchi, Yoko ; Yamamoto, Masayuki ; Yoneda, Misako ; Yonekura, Yohei ; Yoshida, Shigehiro ; Zabierowski, Suzan E. ; Zhang, Peter G. ; Zhao, Xiaobei ; Zucchelli, Silvia ; Summers, Kim M. ; Suzuki, Harukazu ; Daub, Carsten O. ; Kawai, Jun ; Heutink, Peter ; Hide, Winston ; Freeman, Tom C. ; Lenhard, Boris ; Bajic, Vladimir B. ; Taylor, Martin S. ; Makeev, Vsevolod J. ; Sandelin, Albin ; Hume, David A. ; Carninci, Piero ; Hayashizaki, Yoshihide. / The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome. In: PLoS Biology. 2015 ; Vol. 13, No. 12.
@article{f9d4d786ceb44eabbc45a382411f853e,
title = "The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome",
abstract = "X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X’s gene content, gene expression, and evolution.",
author = "Hurst, {Laurence D.} and Ghanbarian, {Avazeh T.} and Forrest, {Alistair R R} and Lukasz Huminiecki and Michael Rehli and {Kenneth Baillie}, J. and {de Hoon}, {Michiel J L} and Vanja Haberle and Timo Lassmann and Kulakovskiy, {Ivan V.} and Marina Lizio and Masayoshi Itoh and Robin Andersson and Mungall, {Christopher J.} and Meehan, {Terrence F.} and Sebastian Schmeier and Nicolas Bertin and Mette J{\o}rgensen and Emmanuel Dimont and Erik Arner and Christian Schmidl and Ulf Schaefer and Medvedeva, {Yulia A.} and Charles Plessy and Morana Vitezic and Jessica Severin and Semple, {Colin A.} and Yuri Ishizu and Young, {Robert S.} and Margherita Francescatto and Intikhab Alam and Davide Albanese and Altschuler, {Gabriel M.} and Takahiro Arakawa and Archer, {John A C} and Peter Arner and Magda Babina and Sarah Baker and Balwierz, {Piotr J.} and Beckhouse, {Anthony G.} and Pradhan, {Swati Bhatt} and Blake, {Judith A.} and Antje Blumenthal and Beatrice Bodega and Alessandro Bonetti and James Briggs and Frank Brombacher and {Maxwell Burroughs}, A. and Andrea Califano and Cannistraci, {Carlo V.} and Daniel Carbajo and Yun Chen and Marco Chierici and Yari Ciani and Clevers, {Hans C.} and Emiliano Dalla and Davis, {Carrie A.} and Michael Detmar and Diehl, {Alexander D.} and Taeko Dohi and Finn Drabl{\o}s and Edge, {Albert S B} and Matthias Edinger and Karl Ekwall and Mitsuhiro Endoh and Hideki Enomoto and Michela Fagiolini and Lynsey Fairbairn and Hai Fang and Farach-Carson, {Mary C.} and Faulkner, {Geoffrey J.} and Favorov, {Alexander V.} and Fisher, {Malcolm E.} and Frith, {Martin C.} and Rie Fujita and Shiro Fukuda and Cesare Furlanello and Masaaki Furuno and Furusawa, {Jun ichi} and Geijtenbeek, {Teunis B.} and Andrew Gibson and Thomas Gingeras and Daniel Goldowitz and Julian Gough and Sven Guhl and Reto Guler and Stefano Gustincich and Ha, {Thomas J.} and Masahide Hamaguchi and Mitsuko Hara and Matthias Harbers and Jayson Harshbarger and Akira Hasegawa and Yuki Hasegawa and Takehiro Hashimoto and Meenhard Herlyn and Hitchens, {Kelly J.} and {Ho Sui}, {Shannan J.} and Hofmann, {Oliver M.} and Ilka Hoof and Fumi Hori and Lukasz Huminiecki and Kei Iida and Tomokatsu Ikawa and Jankovic, {Boris R.} and Hui Jia and Anagha Joshi and Giuseppe Jurman and Bogumil Kaczkowski and Chieko Kai and Kaoru Kaida and Ai Kaiho and Kazuhiro Kajiyama and Kanamori, {Mutsumi Katayama} and Kasianov, {Artem S.} and Takeya Kasukawa and Shintaro Katayama and Sachi Kato and Shuji Kawaguchi and Hiroshi Kawamoto and Kawamura, {Yuki I.} and Tsugumi Kawashima and Kempfle, {Judith S.} and Kenna, {Tony J.} and Juha Kere and Khachigian, {Levon M.} and Toshio Kitamura and {Peter Klinken}, S. and Knox, {Alan J.} and Miki Kojima and Soichi Kojima and Naoto Kondo and Haruhiko Koseki and Shigeo Koyasu and Sarah Krampitz and Atsutaka Kubosaki and Kwon, {Andrew T.} and Laros, {Jeroen F J} and Weonju Lee and Andreas Lennartsson and Kang Li and Berit Lilje and Leonard Lipovich and Mackay, {Alan sim} and Riichiroh Manabe and Mar, {Jessica C.} and Benoit Marchand and Anthony Mathelier and Niklas Mejhert and Alison Meynert and Yosuke Mizuno and {de Lima Morais}, {David A.} and Hiromasa Morikawa and Mitsuru Morimoto and Kazuyo Moro and Efthymios Motakis and Hozumi Motohashi and Mummery, {Christine L.} and Mitsuyoshi Murata and Nagao, {Sayaka Sato} and Yutaka Nakachi and Fumio Nakahara and Toshiyuki Nakamura and Yukio Nakamura and Kenichi Nakazato and {van Nimwegen}, Erik and Noriko Ninomiya and Hiromi Nishiyori and Shohei Noma and Tadasuke Nozaki and Soichi Ogishima and Naganari Ohkura and Hiroko Ohmiya and Hiroshi Ohno and Mitsuhiro Ohshima and Okada, {Mariko Hatakeyama} and Yasushi Okazaki and Valerio Orlando and Ovchinnikov, {Dmitry A.} and Arnab Pain and Robert Passier and Margaret Patrikakis and Helena Persson and Silvano Piazza and Prendergast, {James G D} and Rackham, {Owen J L} and Ramilowski, {Jordan A.} and Mamoon Rashid and Timothy Ravasi and Patrizia Rizzu and Marco Roncador and Sugata Roy and Rye, {Morten B.} and Eri Saijyo and Antti Sajantila and Akiko Saka and Shimon Sakaguchi and Mizuho Sakai and Hiroki Sato and Hironori Satoh and Suzana Savvi and Alka Saxena and Claudio Schneider and Schultes, {Erik A.} and Schulze-Tanzil, {Gundula G.} and Anita Schwegmann and Thierry Sengstag and Guojun Sheng and Hisashi Shimoji and Yishai Shimoni and Shin, {Jay W.} and Christophe Simon and Daisuke Sugiyama and Takaaki Sugiyama and Masanori Suzuki and Naoko Suzuki and Swoboda, {Rolf K.} and {'t Hoen}, {Peter A C} and Michihira Tagami and Naoko Takahashi and Jun Takai and Hiroshi Tanaka and Hideki Tatsukawa and Zuotian Tatum and Mark Thompson and Hiroo Toyoda and Tetsuro Toyoda and Eivind Valen and {van de Wetering}, Marc and {van den Berg}, {Linda M.} and Roberto Verardo and Dipti Vijayan and Vorontsov, {Ilya E.} and Wasserman, {Wyeth W.} and Shoko Watanabe and Wells, {Christine A.} and Winteringham, {Louise N.} and Ernst Wolvetang and Wood, {Emily J.} and Yoko Yamaguchi and Masayuki Yamamoto and Misako Yoneda and Yohei Yonekura and Shigehiro Yoshida and Zabierowski, {Suzan E.} and Zhang, {Peter G.} and Xiaobei Zhao and Silvia Zucchelli and Summers, {Kim M.} and Harukazu Suzuki and Daub, {Carsten O.} and Jun Kawai and Peter Heutink and Winston Hide and Freeman, {Tom C.} and Boris Lenhard and Bajic, {Vladimir B.} and Taylor, {Martin S.} and Makeev, {Vsevolod J.} and Albin Sandelin and Hume, {David A.} and Piero Carninci and Yoshihide Hayashizaki",
year = "2015",
month = "12",
day = "18",
doi = "10.1371/journal.pbio.1002315",
language = "English (US)",
volume = "13",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome

AU - Hurst, Laurence D.

AU - Ghanbarian, Avazeh T.

AU - Forrest, Alistair R R

AU - Huminiecki, Lukasz

AU - Rehli, Michael

AU - Kenneth Baillie, J.

AU - de Hoon, Michiel J L

AU - Haberle, Vanja

AU - Lassmann, Timo

AU - Kulakovskiy, Ivan V.

AU - Lizio, Marina

AU - Itoh, Masayoshi

AU - Andersson, Robin

AU - Mungall, Christopher J.

AU - Meehan, Terrence F.

AU - Schmeier, Sebastian

AU - Bertin, Nicolas

AU - Jørgensen, Mette

AU - Dimont, Emmanuel

AU - Arner, Erik

AU - Schmidl, Christian

AU - Schaefer, Ulf

AU - Medvedeva, Yulia A.

AU - Plessy, Charles

AU - Vitezic, Morana

AU - Severin, Jessica

AU - Semple, Colin A.

AU - Ishizu, Yuri

AU - Young, Robert S.

AU - Francescatto, Margherita

AU - Alam, Intikhab

AU - Albanese, Davide

AU - Altschuler, Gabriel M.

AU - Arakawa, Takahiro

AU - Archer, John A C

AU - Arner, Peter

AU - Babina, Magda

AU - Baker, Sarah

AU - Balwierz, Piotr J.

AU - Beckhouse, Anthony G.

AU - Pradhan, Swati Bhatt

AU - Blake, Judith A.

AU - Blumenthal, Antje

AU - Bodega, Beatrice

AU - Bonetti, Alessandro

AU - Briggs, James

AU - Brombacher, Frank

AU - Maxwell Burroughs, A.

AU - Califano, Andrea

AU - Cannistraci, Carlo V.

AU - Carbajo, Daniel

AU - Chen, Yun

AU - Chierici, Marco

AU - Ciani, Yari

AU - Clevers, Hans C.

AU - Dalla, Emiliano

AU - Davis, Carrie A.

AU - Detmar, Michael

AU - Diehl, Alexander D.

AU - Dohi, Taeko

AU - Drabløs, Finn

AU - Edge, Albert S B

AU - Edinger, Matthias

AU - Ekwall, Karl

AU - Endoh, Mitsuhiro

AU - Enomoto, Hideki

AU - Fagiolini, Michela

AU - Fairbairn, Lynsey

AU - Fang, Hai

AU - Farach-Carson, Mary C.

AU - Faulkner, Geoffrey J.

AU - Favorov, Alexander V.

AU - Fisher, Malcolm E.

AU - Frith, Martin C.

AU - Fujita, Rie

AU - Fukuda, Shiro

AU - Furlanello, Cesare

AU - Furuno, Masaaki

AU - Furusawa, Jun ichi

AU - Geijtenbeek, Teunis B.

AU - Gibson, Andrew

AU - Gingeras, Thomas

AU - Goldowitz, Daniel

AU - Gough, Julian

AU - Guhl, Sven

AU - Guler, Reto

AU - Gustincich, Stefano

AU - Ha, Thomas J.

AU - Hamaguchi, Masahide

AU - Hara, Mitsuko

AU - Harbers, Matthias

AU - Harshbarger, Jayson

AU - Hasegawa, Akira

AU - Hasegawa, Yuki

AU - Hashimoto, Takehiro

AU - Herlyn, Meenhard

AU - Hitchens, Kelly J.

AU - Ho Sui, Shannan J.

AU - Hofmann, Oliver M.

AU - Hoof, Ilka

AU - Hori, Fumi

AU - Huminiecki, Lukasz

AU - Iida, Kei

AU - Ikawa, Tomokatsu

AU - Jankovic, Boris R.

AU - Jia, Hui

AU - Joshi, Anagha

AU - Jurman, Giuseppe

AU - Kaczkowski, Bogumil

AU - Kai, Chieko

AU - Kaida, Kaoru

AU - Kaiho, Ai

AU - Kajiyama, Kazuhiro

AU - Kanamori, Mutsumi Katayama

AU - Kasianov, Artem S.

AU - Kasukawa, Takeya

AU - Katayama, Shintaro

AU - Kato, Sachi

AU - Kawaguchi, Shuji

AU - Kawamoto, Hiroshi

AU - Kawamura, Yuki I.

AU - Kawashima, Tsugumi

AU - Kempfle, Judith S.

AU - Kenna, Tony J.

AU - Kere, Juha

AU - Khachigian, Levon M.

AU - Kitamura, Toshio

AU - Peter Klinken, S.

AU - Knox, Alan J.

AU - Kojima, Miki

AU - Kojima, Soichi

AU - Kondo, Naoto

AU - Koseki, Haruhiko

AU - Koyasu, Shigeo

AU - Krampitz, Sarah

AU - Kubosaki, Atsutaka

AU - Kwon, Andrew T.

AU - Laros, Jeroen F J

AU - Lee, Weonju

AU - Lennartsson, Andreas

AU - Li, Kang

AU - Lilje, Berit

AU - Lipovich, Leonard

AU - Mackay, Alan sim

AU - Manabe, Riichiroh

AU - Mar, Jessica C.

AU - Marchand, Benoit

AU - Mathelier, Anthony

AU - Mejhert, Niklas

AU - Meynert, Alison

AU - Mizuno, Yosuke

AU - de Lima Morais, David A.

AU - Morikawa, Hiromasa

AU - Morimoto, Mitsuru

AU - Moro, Kazuyo

AU - Motakis, Efthymios

AU - Motohashi, Hozumi

AU - Mummery, Christine L.

AU - Murata, Mitsuyoshi

AU - Nagao, Sayaka Sato

AU - Nakachi, Yutaka

AU - Nakahara, Fumio

AU - Nakamura, Toshiyuki

AU - Nakamura, Yukio

AU - Nakazato, Kenichi

AU - van Nimwegen, Erik

AU - Ninomiya, Noriko

AU - Nishiyori, Hiromi

AU - Noma, Shohei

AU - Nozaki, Tadasuke

AU - Ogishima, Soichi

AU - Ohkura, Naganari

AU - Ohmiya, Hiroko

AU - Ohno, Hiroshi

AU - Ohshima, Mitsuhiro

AU - Okada, Mariko Hatakeyama

AU - Okazaki, Yasushi

AU - Orlando, Valerio

AU - Ovchinnikov, Dmitry A.

AU - Pain, Arnab

AU - Passier, Robert

AU - Patrikakis, Margaret

AU - Persson, Helena

AU - Piazza, Silvano

AU - Prendergast, James G D

AU - Rackham, Owen J L

AU - Ramilowski, Jordan A.

AU - Rashid, Mamoon

AU - Ravasi, Timothy

AU - Rizzu, Patrizia

AU - Roncador, Marco

AU - Roy, Sugata

AU - Rye, Morten B.

AU - Saijyo, Eri

AU - Sajantila, Antti

AU - Saka, Akiko

AU - Sakaguchi, Shimon

AU - Sakai, Mizuho

AU - Sato, Hiroki

AU - Satoh, Hironori

AU - Savvi, Suzana

AU - Saxena, Alka

AU - Schneider, Claudio

AU - Schultes, Erik A.

AU - Schulze-Tanzil, Gundula G.

AU - Schwegmann, Anita

AU - Sengstag, Thierry

AU - Sheng, Guojun

AU - Shimoji, Hisashi

AU - Shimoni, Yishai

AU - Shin, Jay W.

AU - Simon, Christophe

AU - Sugiyama, Daisuke

AU - Sugiyama, Takaaki

AU - Suzuki, Masanori

AU - Suzuki, Naoko

AU - Swoboda, Rolf K.

AU - 't Hoen, Peter A C

AU - Tagami, Michihira

AU - Takahashi, Naoko

AU - Takai, Jun

AU - Tanaka, Hiroshi

AU - Tatsukawa, Hideki

AU - Tatum, Zuotian

AU - Thompson, Mark

AU - Toyoda, Hiroo

AU - Toyoda, Tetsuro

AU - Valen, Eivind

AU - van de Wetering, Marc

AU - van den Berg, Linda M.

AU - Verardo, Roberto

AU - Vijayan, Dipti

AU - Vorontsov, Ilya E.

AU - Wasserman, Wyeth W.

AU - Watanabe, Shoko

AU - Wells, Christine A.

AU - Winteringham, Louise N.

AU - Wolvetang, Ernst

AU - Wood, Emily J.

AU - Yamaguchi, Yoko

AU - Yamamoto, Masayuki

AU - Yoneda, Misako

AU - Yonekura, Yohei

AU - Yoshida, Shigehiro

AU - Zabierowski, Suzan E.

AU - Zhang, Peter G.

AU - Zhao, Xiaobei

AU - Zucchelli, Silvia

AU - Summers, Kim M.

AU - Suzuki, Harukazu

AU - Daub, Carsten O.

AU - Kawai, Jun

AU - Heutink, Peter

AU - Hide, Winston

AU - Freeman, Tom C.

AU - Lenhard, Boris

AU - Bajic, Vladimir B.

AU - Taylor, Martin S.

AU - Makeev, Vsevolod J.

AU - Sandelin, Albin

AU - Hume, David A.

AU - Carninci, Piero

AU - Hayashizaki, Yoshihide

PY - 2015/12/18

Y1 - 2015/12/18

N2 - X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X’s gene content, gene expression, and evolution.

AB - X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X’s gene content, gene expression, and evolution.

UR - http://www.scopus.com/inward/record.url?scp=84969295765&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84969295765&partnerID=8YFLogxK

U2 - 10.1371/journal.pbio.1002315

DO - 10.1371/journal.pbio.1002315

M3 - Article

VL - 13

JO - PLoS Biology

JF - PLoS Biology

SN - 1544-9173

IS - 12

M1 - e1002315

ER -