Origins of Life and Evolution of Biospheres

, Volume 41, Issue 6, pp 587–607 | Cite as

“Hypothesis for the Modern RNA World”: A pervasive Non-coding RNA-Based Genetic Regulation is a Prerequisite for the Emergence of Multicellular Complexity

  • Irma Lozada-Chávez
  • Peter F. Stadler
  • Sonja J. Prohaska


The transitions to multicellularity mark the most pivotal and distinctive events in life’s history on Earth. Although several transitions to “simple” multicellularity (SM) have been recorded in both bacterial and eukaryotic clades, transitions to complex multicellularity (CM) have only happened a few times in eukaryotes. A large number of cell types (associated with large body size), increased energy consumption per gene expressed, and an increment of non-protein-coding DNA positively correlate with CM. These three factors can indeed be understood as the causes and consequences of the regulation of gene expression. Here, we discuss how a vast expansion of non-protein-coding RNA (ncRNAs) regulators rather than large numbers of novel protein regulators can easily contribute to the emergence of CM. We also propose that the evolutionary advantage of RNA-based gene regulation derives from the robustness of the RNA structure that makes it easy to combine genetic drift with functional exploration. We describe a model which aims to explain how the evolutionary dynamic of ncRNAs becomes dominated by the accessibility of advantageous mutations to innovate regulation in complex multicellular organisms. The information and models discussed here outline the hypothesis that pervasive ncRNA-based regulatory systems, only capable of being expanded and explored in higher eukaryotes, are prerequisite to complex multicellularity. Thereby, regulatory RNA molecules in Eukarya have allowed intensification of morphological complexity by stabilizing critical phenotypes and controlling developmental precision. Although the origin of RNA on early Earth is still controversial, it is becoming clear that once RNA emerged into a protocellular system, its relevance within the evolution of biological systems has been greater than we previously thought.


Modern RNA world Multicellular complexity Eukaryote evolution Genome complexity Non-coding RNA Gene regulation 



IL-C is funded by the fellowship 185993 from the National Council of Science and Technology of Mexico. We thank Christian Arnold and an anonymous referee for valuable comments and suggestions. We dedicate this article to the memory of Lynn Margulis, whose work has allowed us to go forward on the understanding of the origin and evolution of complex life on Earth.


  1. Aguirre J, Rios-Momberg M, Hewitt D et al (2005) Reactive oxygen species and development in microbial eukaryotes. Trends Microbiol 13:111–118PubMedGoogle Scholar
  2. Amar L, Chen CL, Zhou H et al (2009) Genome-wide evolutionary analysis of the noncoding RNA genes and noncoding DNA of Paramecium tetraurelia. RNA 15:503–514PubMedGoogle Scholar
  3. Arendt D, Christodoulou F, Raible F et al (2010) Ancient animal microRNAs and the evolution of tissue identity. Nature 463:1084–U1105PubMedGoogle Scholar
  4. Babu MM, Teichmann SA, Aravind L (2006) Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J Mol Biol 358:614–633Google Scholar
  5. Banfield W, Woke PA, MacKay CM, Cooper HL (1965) Mosquito transmission of a reticulum cell sarcoma of hamsters. Science 148:1239–1240PubMedGoogle Scholar
  6. Bartel DP, Nodine MD (2010) MicroRNAs prevent precocious gene expression and enable pattern formation during plant embryogenesis. Genes Dev 24:2678–2692PubMedGoogle Scholar
  7. Bell G, Mooers AO (1997) Size and complexity among multicellular organisms. Biol J Linn Soc 60:345–363Google Scholar
  8. Benton MJ, Ayala FJ (2003) Dating the tree of life. Science 300:1698–1700PubMedGoogle Scholar
  9. Bernstein E, Kim SY, Carmell MA et al (2003) Dicer is essential for mouse development. Nat Genet 35:215–217PubMedGoogle Scholar
  10. Berretta J, Morillon A (2009) Pervasive transcription constitutes a new level of eukaryotic genome regulation. Embo Reports 10:973–982PubMedGoogle Scholar
  11. Bistis GN, Perkins David D, Read Nick D (2003) Different cell types in Neurospora crassa. Fungal Genetics Newsletter 50:17–19Google Scholar
  12. Blackstone NW (2000) Redox control and the evolution of multicellularity. Bioessays 22:947–953PubMedGoogle Scholar
  13. Bocobza SE, Aharoni A (2008) Switching the light on plant riboswitches. Trends Plant Sci 13:526–533PubMedGoogle Scholar
  14. Bonner JT (1998) The origins of multicellularity. Integr Biol 1:28–36Google Scholar
  15. Bonner JT (2004) Perspective: the size-complexity rule. Evolution 58:1883–1890PubMedGoogle Scholar
  16. Bowman JL, Floyd SK (2007) The ancestral developmental tool kit of land plants. Int J Plant Sci 168:1–35Google Scholar
  17. Cabili MN, Trapnell C, Goff L et al (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25:1915–1927PubMedGoogle Scholar
  18. Carrington JC, Allen E, Xie ZX et al (2004) Evolution of microRNA genes by inverted duplication of target gene sequences in Arabidopsis thaliana. Nat Genet 36:1282–1290PubMedGoogle Scholar
  19. Carrington JC, Fahlgren N, Howell MD et al (2007) High-throughput sequencing of Arabidopsis microRNAs: evidence for frequent birth and death of MIRNA genes. PLoS One 2:e219PubMedGoogle Scholar
  20. Carrington JC, Cuperus JT, Fahlgren N (2011) Evolution and functional diversification of MIRNA genes. Plant Cell 23:431–442PubMedGoogle Scholar
  21. Carroll SB (2001) Chance and necessity: the evolution of morphological complexity and diversity. Nature 409:1102–1109PubMedGoogle Scholar
  22. Cases I, de Lorenzo V, Ouzounis CA (2003) Transcription regulation and environmental adaptation in bacteria. Trends Microbiol 11:248–253PubMedGoogle Scholar
  23. Cheah MT, Wachter A, Sudarsan N et al (2007) Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature 447:497–500PubMedGoogle Scholar
  24. Chu C, Qu K, Zhong FL et al (2011) Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Molecular Cell 44:667–678PubMedGoogle Scholar
  25. Clark MB, Amaral PP, Schlesinger FJ et al (2011) The reality of pervasive transcription. Plos Biology 9:e1000625PubMedGoogle Scholar
  26. Cobb BS, Nesterova TB, Thompson E et al (2005) T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med 201:1367–1373PubMedGoogle Scholar
  27. Cock JM, Sterck L, Rouze P et al (2010) The Ectocarpus genome and the independent evolution of multicellularity in brown algae. Nature 465:617–621PubMedGoogle Scholar
  28. Condorelli G, Dimmeler S (2008) MicroRNAs: components of an integrated system controlling cardiac development, physiology, and disease pathogenesis. Cardiovasc Res 79:551–552PubMedGoogle Scholar
  29. Costa FF (2005) Non-coding RNAs: new players in eukaryotic biology. Gene 357:83–94PubMedGoogle Scholar
  30. de Meaux J, Hu JY, Tartler U et al (2008) Structurally different alleles of the ath-MIR824 microRNA precursor are maintained at high frequency in Arabidopsis thaliana. Proc Natl Acad Sci U S A 105:8994–8999PubMedGoogle Scholar
  31. DeLong JP, Okie JG, Moses ME et al (2010) Shifts in metabolic scaling, production, and efficiency across major evolutionary transitions of life. Proc Natl Acad Sci U S A 107:12941–12945PubMedGoogle Scholar
  32. Deng XW, Li L, Wang XF et al (2006) Genome-wide transcription analyses in rice using tiling microarrays. Nat Genet 38:124–129PubMedGoogle Scholar
  33. Donoghue PCJ, Heimberg AM, Sempere LF et al (2008) MicroRNAs and the advent of vertebrate morphological complexity. Proc Natl Acad Sci U S A 105:2946–2950PubMedGoogle Scholar
  34. Duret L, Chureau C, Samain S et al (2006) The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science 312:1653–1655PubMedGoogle Scholar
  35. Erwin DH (2009) Early origin of the bilaterian developmental toolkit. Phil Trans Roy Soc B Biol Sci 364:2253–2261Google Scholar
  36. Fontana W, Schuster P (1998) Continuity in evolution: on the nature of transitions. Science 280:1451–1455PubMedGoogle Scholar
  37. Gerstein MB, Mu XJ, Lu ZJ et al (2011) Analysis of genomic variation in non-coding elements using population-scale sequencing data from the 1000 Genomes Project. Nucleic Acids Res 39:7058–7076PubMedGoogle Scholar
  38. Gingeras TR, Kapranov P, Cheng J et al (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484–1488PubMedGoogle Scholar
  39. Giraldez AJ, Cinalli RM, Glasner ME et al (2005) MicroRNAs regulate brain morphogenesis in zebrafish. Science 308:833–838PubMedGoogle Scholar
  40. Gregory TR (2005) Synergy between sequence and size in large-scale genomics. Nat Rev Genet 6:699–708PubMedGoogle Scholar
  41. Grosberg RK, Strathmann RR (2007) The evolution of multicellularity: a minor major transition? Annu Rev Ecol Evol Syst 38:621–654Google Scholar
  42. Gruber AR, Kilgus C, Mosig A et al (2008) Arthropod 7SK RNA. Mol Biol Evol 25:1923–1930PubMedGoogle Scholar
  43. Guo XY, Zhang ZL, Gerstein MB et al (2009) Small RNAs originated from pseudogenes: cis- or trans-Acting? Plos Comput Biol 5:e1000449PubMedGoogle Scholar
  44. Hampl V, Hug L, Leigh JW et al (2009) Phylogenomic analyses support the monophyly of Excavata and resolve relationships among eukaryotic "supergroups". Proc Natl Acad Sci U S A 106:3859–3864PubMedGoogle Scholar
  45. Harfe BD, McManus MT, Mansfield JH et al (2005) The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A 102:10898–10903PubMedGoogle Scholar
  46. Hedges SB (2002) The origin and evolution of model organisms. Nat Rev Genet 3:838–849PubMedGoogle Scholar
  47. Hedges SB, Blair JE, Venturi ML et al (2004) A molecular timescale of eukaryote evolution and the rise of complex multicellular life. BMC Evol Biol 4:2PubMedGoogle Scholar
  48. Hiller M, Findeiss S, Lein S et al (2009) Conserved introns reveal novel transcripts in Drosophila melanogaster. Genome Res 19:1289–1300PubMedGoogle Scholar
  49. Holland HD (2006) The oxygenation of the atmosphere and oceans. Phil Trans Roy Soc B Biol Sci 361:903–915Google Scholar
  50. Hornstein E, Shomron N (2006) Canalization of development by microRNAs. Nat Genet 38:S20–S24PubMedGoogle Scholar
  51. Huynen MA (1996) Exploring phenotype space through neutral evolution. J Mol Evol 43:165–169PubMedGoogle Scholar
  52. Huynen MA, Stadler PF, Fontana W (1996) Smoothness within ruggedness: the role of neutrality in adaptation. Proc Natl Acad Sci U S A 93:397–401PubMedGoogle Scholar
  53. Jacquier A (2009) The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat Rev Genet 10:833–844PubMedGoogle Scholar
  54. Joyce GF (2002) The antiquity of RNA-based evolution. Nature 418:214–221PubMedGoogle Scholar
  55. Kaiser D (2001) Building a multicellular organism. Annu Rev Genet 35:103–123PubMedGoogle Scholar
  56. Kapranov P, St Laurent G, Raz T et al (2010) The majority of total nuclear-encoded non-ribosomal RNA in a human cell is 'dark matter' un-annotated RNA. BMC Biol 8:149PubMedGoogle Scholar
  57. Kazazian HH (2004) Mobile elements: drivers of genome evolution. Science 303:1626–1632PubMedGoogle Scholar
  58. Kim, ED and Sung, S (2011) Long noncoding RNA: unveiling hidden layer of gene regulatory networks. Trends Plant Sci (in press)Google Scholar
  59. Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10:126–139PubMedGoogle Scholar
  60. King N (2004) The unicellular ancestry of animal development. Dev Cell 7:313–325PubMedGoogle Scholar
  61. King N, Westbrook MJ, Young SL et al (2008) The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 451:783–788PubMedGoogle Scholar
  62. Kishore S, Stamm S (2006) Regulation of alternative splicing by snoRNAs. Cold Spring Harb Symp Quant Biol 71:329–334PubMedGoogle Scholar
  63. Knoll AH (2011) The multiple origins of complex multicellularity. Annu Rev Earth Planet Sci 39:217–239Google Scholar
  64. Kolter R, Branda SS, Gonzalez-Pastor JE et al (2001) Fruiting body formation by Bacillus subtilis. Proc Natl Acad Sci U S A 98:11621–11626PubMedGoogle Scholar
  65. Kong FX, Yang Z, Yang Z et al (2009) Benefits and costs of the grazer-induced colony formation in Microcystis aeruginosa. Ann Limnol-Int J Lim 45:203–208Google Scholar
  66. Konstantinidis KT, Tiedje JM (2004) Trends between gene content and genome size in prokaryotic species with larger genomes. Proc Natl Acad Sci U S A 101:3160–3165PubMedGoogle Scholar
  67. Koonin EV, Fedorova ND, Jackson JD et al (2004) A comprehensive evolutionary classification of proteins encoded in complete eukaryotic genomes. Genome Biol 5:R7PubMedGoogle Scholar
  68. Lai EC, Liu N, Okamura K et al (2008) The evolution and functional diversification of animal microRNA genes. Cell Res 18:985–996PubMedGoogle Scholar
  69. Lane N, Martin W (2010) The energetics of genome complexity. Nature 467:929–934PubMedGoogle Scholar
  70. Lesser MP (2006) Oxidative stress in marine environments: biochemistry and physiological ecology. Annu Rev Physiol 68:253–278PubMedGoogle Scholar
  71. Lin HF, Gangaraju VK (2009) MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol 10:116–125PubMedGoogle Scholar
  72. Liu Y, Lee HC, Li LD et al (2010) Diverse pathways generate microRNA-like RNAs and dicer-independent small interfering RNAs in fungi. Molecular Cell 38:803–814PubMedGoogle Scholar
  73. Lozada-Chavez I, Janga SC, Collado-Vides J (2006) Bacterial regulatory networks are extremely flexible in evolution. Nucleic Acids Res 34:3434–3445PubMedGoogle Scholar
  74. Lozada-Chavez I, Angarica VE, Collado-Vides J et al (2008) The role of DNA-binding specificity in the evolution of bacterial regulatory networks. J Mol Biol 379:627–643PubMedGoogle Scholar
  75. Lu J, Fu YG, Kumar S et al (2008) Adaptive evolution of newly emerged micro-RNA genes in Drosophila. Mol Biol Evol 25:929–938PubMedGoogle Scholar
  76. Lurling M, Van Donk E (1999) Grazer-induced colony formation in Scenedesmus acutus (Chlorophyceae): ecomorph expression at different temperatures. J Phycol 35:1120–1126Google Scholar
  77. Lynch M (2006) The origins of eukaryotic gene structure. Mol Biol Evol 23:450–468PubMedGoogle Scholar
  78. Lynch M, Conery JS (2003) The origins of genome complexity. Science 302:1401–1404PubMedGoogle Scholar
  79. Lynch M, Bobay LM, Catania F et al (2011) The repatterning of eukaryotic genomes by random genetic drift. Annu Rev Genomics Hum Genet 12:347–366PubMedGoogle Scholar
  80. Marques AC, Ponting CP (2009) Catalogues of mammalian long noncoding RNAs: modest conservation and incompleteness. Genome Biol 10:R124PubMedGoogle Scholar
  81. Martinez-Antonio A, Collado-Vides J (2003) Identifying global regulators in transcriptional regulatory networks in bacteria. Curr Opin Microbiol 6:482–489PubMedGoogle Scholar
  82. Mattick JS, Taft RJ, Pheasant M (2007) The relationship between non-protein-coding DNA and eukaryotic complexity. Bioessays 29:288–299PubMedGoogle Scholar
  83. Mattick JS, Amaral PP, Dinger ME et al (2008) The eukaryotic genome as an RNA machine. Science 319:1787–1789PubMedGoogle Scholar
  84. Mattick JS, Mercer TR, Dinger ME (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159PubMedGoogle Scholar
  85. McCarthy MC, Enquist BJ (2005) Organismal size, metabolism and the evolution of complexity in metazoans. Evol Ecol Res 7:681–696Google Scholar
  86. Medina M, Collins AG, Taylor JW, Valentine JW, Lipps JH, Amaral-Zettler L, Sogin ML (2003) Phylogeny of Opisthokonta and the evolution of multicellularity and complexity in Fungi and Metazoa. Int J Astrobiol 2:203–211Google Scholar
  87. Millar AA, Waterhouse PM (2005) Plant and animal microRNAs: similarities and differences. Funct Integr Genomics 5:129–135PubMedGoogle Scholar
  88. Mosig A, Zhu L, Stadler PF (2009) Customized strategies for discovering distant ncRNA homologs. Brief Funct Genomic Proteomic 8:451–460PubMedGoogle Scholar
  89. Niklas KJ (2000) The evolution of plant body plans - A biomechanical perspective. Ann Bot 85:411–438Google Scholar
  90. Nilsen TW, Graveley BR (2010) Expansion of the eukaryotic proteome by alternative splicing. Nature 463:457–463PubMedGoogle Scholar
  91. Ochman H, Davalos LM (2006) The nature and dynamics of bacterial genomes. Science 311:1730–1733PubMedGoogle Scholar
  92. Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246:96–98PubMedGoogle Scholar
  93. Ohta T (1992) The nearly neutral theory of molecular evolution. Annu Rev Ecol Syst 23:263–286Google Scholar
  94. Pain A, Mourier T, Carret C et al (2008) Genome-wide discovery and verification of novel structured RNAs in Plasmodium falciparum. Genome Res 18:281–292PubMedGoogle Scholar
  95. Pauli A, Rinn JL, Schier AF (2011) Non-coding RNAs as regulators of embryogenesis. Nat Rev Genet 12:136–149PubMedGoogle Scholar
  96. Pearse AM, Swift K (2006) Transmission of devil facial-tumour disease - An uncanny similarity in the karyotype of these malignant tumours means that they could be infective. Nature 439:549–549PubMedGoogle Scholar
  97. Peterlin BM, Brogie JE, Price DH (2012) 7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription. Wiley Interdiscip Rev RNA 3:92–103PubMedGoogle Scholar
  98. Peterson KJ, Dietrich MR, McPeek MA (2009) MicroRNAs and metazoan macroevolution: insights into canalization, complexity, and the Cambrian explosion. Bioessays 31:736–747PubMedGoogle Scholar
  99. Ponting CP, Ponjavic J, Lunter G (2007) Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Res 17:556–565PubMedGoogle Scholar
  100. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641PubMedGoogle Scholar
  101. Rajewsky N, Chen K (2007) The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 8:93–103PubMedGoogle Scholar
  102. Ren B (2010) Enhancers make non-coding RNA. Nature 465:173–174PubMedGoogle Scholar
  103. Repoila F, Darfeuille F (2009) Small regulatory non-coding RNAs in bacteria: physiology and mechanistic aspects. Biology of the Cell 101:117–131PubMedGoogle Scholar
  104. Robertson MP, Joyce GF (2010) The origins of the RNA world. Cold Spring Harb Perspect Biol. doi: 10.1101/cshperspect.a003608
  105. Rokas A (2008) The origins of multicellularity and the early history of the genetic toolkit for animal development. Annu Rev Genet 42:235–251PubMedGoogle Scholar
  106. Rose D, Hiller M, Schutt K et al (2011) Computational discovery of human coding and non-coding transcripts with conserved splice sites. Bioinformatics 27:1894–1900PubMedGoogle Scholar
  107. Roush S, Slack FJ (2008) The let-7 family of microRNAs. Trends Cell Biol 18:505–516PubMedGoogle Scholar
  108. Schuster P, Fontana W, Stadler PF et al (1994) From sequences to shapes and back: a case study in RNA secondary structures. Proc Biol Sci 255:279–284PubMedGoogle Scholar
  109. Scott MS, Ono M (2011) From snoRNA to miRNA: dual function regulatory non-coding RNAs. Biochimie 93:1987–1992PubMedGoogle Scholar
  110. Sharma CM, Hoffmann S, Darfeuille F et al (2010) The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464:250–255PubMedGoogle Scholar
  111. Specht CD, Bartlett ME (2009) Flower evolution: the origin and subsequent diversification of the angiosperm flower. Annu Rev Ecol Evol Syst 40:217–243Google Scholar
  112. Spector DL, Prasanth KV (2007) Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum. Genes Dev 21:11–42PubMedGoogle Scholar
  113. Spector DL, Wilusz JE, Sunwoo H (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23:1494–1504PubMedGoogle Scholar
  114. Srivastava M, Simakov O, Chapman J et al (2010) The Amphimedon queenslandica genome and the evolution of animal complexity. Nature 466:720–U723PubMedGoogle Scholar
  115. Storz G, Waters LS (2009) Regulatory RNAs in Bacteria. Cell 136:615–628PubMedGoogle Scholar
  116. Strathmann R (1991) From metazoan to protist via competition among cell lineages. Evol Theor 10:67–70Google Scholar
  117. Sudarsan N, Barrick JE, Breaker RR (2003) Metabolite-binding RNA domains are present in the genes of eukaryotes. RNA 9:644–647PubMedGoogle Scholar
  118. Tisseur M, Kwapisz M, Morillon A (2011) Pervasive transcription - Lessons from yeast. Biochimie 93:1889–1896PubMedGoogle Scholar
  119. Tomitani A, Knoll AH, Cavanaugh CM et al (2006) The evolutionary diversification of cyanobacteria: molecular-phylogenetic and paleontological perspectives. Proc Natl Acad Sci U S A 103:5442–5447PubMedGoogle Scholar
  120. Valentine JW, Collins AG, Meyer CP (1994) Morphological complexity increase in metazoans. Paleobiology 20:131–142Google Scholar
  121. van Bakel H, Nislow C, Blencowe BJ et al (2010) Most "Dark Matter'' transcripts are associated with known genes. Plos Biology 8:e1000371PubMedGoogle Scholar
  122. van Bakel H, Nislow C, Blencowe BJ et al (2011) Response to "The reality of pervasive transcription". Plos Biology 9:e1001102Google Scholar
  123. Velicer GJ, Kroos L, Lenski RE (1998) Loss of social behaviors by Myxococcus xanthus during evolution in an unstructured habitat. Proc Natl Acad Sci U S A 95:12376–12380PubMedGoogle Scholar
  124. Voinnet O (2009) Origin, biogenesis, and activity of plant MicroRNAs. Cell 136:669–687PubMedGoogle Scholar
  125. Wagner A (2005) Energy constraints on the evolution of gene expression. Mol Biol Evol 22:1365–1374PubMedGoogle Scholar
  126. Wang SM, Lu J, Shen Y et al (2008) The birth and death of microRNA genes in Drosophila. Nat Genet 40:351–355PubMedGoogle Scholar
  127. Weiss RA, Murgia C, Pritchard JK et al (2006) Clonal origin and evolution of a transmissible cancer. Cell 126:477–487PubMedGoogle Scholar
  128. Wolpert L, Szathmary E (2002) Multicellularity: evolution and the egg. Nature 420:745–745PubMedGoogle Scholar
  129. Yano Y, Saito R, Yoshida N et al (2004) A new role for expressed pseudogenes as ncRNA: regulation of mRNA stability of its homologous coding gene. J Mol Med-Jmm 82:414–422Google Scholar
  130. Zhao Y, Ransom JF, Li A et al (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129:303–317PubMedGoogle Scholar
  131. Zheng DY, Frankish A, Baertsch R et al (2007) Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and evolution. Genome Res 17:839–851PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Irma Lozada-Chávez
    • 1
    • 2
    • 3
  • Peter F. Stadler
    • 2
    • 3
    • 4
    • 5
    • 6
    • 7
    • 8
  • Sonja J. Prohaska
    • 1
    • 3
  1. 1.Computational EvoDevo GroupUniversity of LeipzigLeipzigGermany
  2. 2.Bioinformatics Group, Department of Computer ScienceUniversity of LeipzigLeipzigGermany
  3. 3.Interdisciplinary Center for BioinformaticsUniversity of LeipzigLeipzigGermany
  4. 4.Max Planck Institute for Mathematics in the SciencesLeipzigGermany
  5. 5.Fraunhofer Institut für Zelltherapie und Immunologie (IZI)LeipzigGermany
  6. 6.Department of Theoretical ChemistryUniversity of ViennaWienAustria
  7. 7.Center For Non-Coding RNA in Technology and HealthUniversity of CopenhagenFrederiksberg CDenmark
  8. 8.Santa Fe InstituteSanta FeUSA

Personalised recommendations