GC Content Heterogeneity

  • Satoshi Oota
Part of the Evolutionary Studies book series (EVOLUS)


Conventional evolutionary theories have been mainly constructed based on coding and its surrounding regions. The genome evolution with its genomic context is scarcely covered by sophisticated evolutionary models. GC content studies have been elaborated long before the “genome sequencing era,” mainly with bacterial genomes. After the intrachromosomal guanine+cytosine (GC) content heterogeneity (isochore) was found as a universal genomic context, various models were proposed to explain the complex and enigmatic isochore evolution. So far, however, no single model can explain the existing data without flaws. I introduced a totally new framework to elucidate evolution of the genomic context: the nonlinear dynamic model or f(x) framework, which potentially expands power of existing evolutionary models.


Isochore Direction of mutations GC-biased gene conversion 


  1. Achaz G, Rodriguez-Verdugo A, Gaut BS, Tenaillon O (2014) The reproducibility of adaptation in the light of experimental evolution with whole genome sequencing. Adv Exp Med Biol 781:211–231PubMedCrossRefGoogle Scholar
  2. Almasy L (2012) The role of phenotype in gene discovery in the whole genome sequencing era. Hum Genet 131:1533–1540PubMedPubMedCentralCrossRefGoogle Scholar
  3. Andolfatto P (2005) Adaptive evolution of non-coding DNA in Drosophila. Nature 437:1149–1152PubMedCrossRefGoogle Scholar
  4. Andujar C, Serrano J, Gomez-Zurita J (2012) Winding up the molecular clock in the genus Carabus (Coleoptera: Carabidae): assessment of methodological decisions on rate and node age estimation. BMC Evol Biol 12:40PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ayala FJ (1999) Molecular clock mirages. BioEssays 21:71–75PubMedCrossRefGoogle Scholar
  6. Baier C, Katoen J-P, Hermanns H (1999) Approximative symbolic model checking of continuous-time Markov chains. In: Baeten JM, Mauw S (eds) CONCUR’99 concurrency theory. Springer, Berlin/Heidelberg, pp 146–161CrossRefGoogle Scholar
  7. Barton NH (1995) Linkage and the limits to natural selection. Genetics 140:821–841PubMedPubMedCentralGoogle Scholar
  8. Baumann K, Stohl A (1997) Validation of a long-range trajectory model using gas balloon tracks from the Gordon Bennett Cup 95. J Appl Meteorol 36:711–720CrossRefGoogle Scholar
  9. Belozersky AN, Spirin AS (1958) A correlation between the compositions of deoxyribonucleic and ribonucleic acids. Nature 182:111–112PubMedCrossRefGoogle Scholar
  10. Berlin S, Brandstrom M, Backstrom N, Axelsson E, Smith NG, Ellegren H (2006) Substitution rate heterogeneity and the male mutation bias. J Mol Evol 62:226–233PubMedCrossRefGoogle Scholar
  11. Bernardi G, Bernardi G (1986) Compositional constraints and genome evolution. J Mol Evol 24:1–11PubMedCrossRefGoogle Scholar
  12. Bernardi G, Ehrlich SD, Thiery JP (1973) The specificity of deoxyribonucleases and their use in nucleotide sequence studies. Nat New Biol 246:36–40PubMedCrossRefGoogle Scholar
  13. Bernardi G, Olofsson B, Filipski J, Zerial M, Salinas J, Cuny G, Meunier-Rotival M, Rodier F (1985) The mosaic genome of warm-blooded vertebrates. Science 228:953–958PubMedCrossRefGoogle Scholar
  14. Bernardi G, Mouchiroud D, Gautier C, Bernardi G (1988) Compositional patterns in vertebrate genomes: conservation and change in evolution. J Mol Evol 28:7–18PubMedCrossRefGoogle Scholar
  15. Bishop RC (2012) Fluid convection, constraint and causation. Interface Focus 2:4–12PubMedCrossRefGoogle Scholar
  16. Bromham L, Penny D (2003) The modern molecular clock. Nat Rev Genet 4:216–224PubMedCrossRefGoogle Scholar
  17. Brown TC, Jiricny J (1988) Different base/base mispairs are corrected with different efficiencies and specificities in monkey kidney cells. Cell 54:705–711PubMedCrossRefGoogle Scholar
  18. Brown CJ, Johnson AK, Daughdrill GW (2010) Comparing models of evolution for ordered and disordered proteins. Mol Biol Evol 27:609–621PubMedCrossRefGoogle Scholar
  19. Charlesworth J, Eyre-Walker A (2007) The other side of the nearly neutral theory, evidence of slightly advantageous back-mutations. Proc Natl Acad Sci U S A 104:16992–16997PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chen J-M, Cooper DN, Chuzhanova N, Ferec C, Patrinos GP (2007) Gene conversion: mechanisms, evolution and human disease. Nat Rev Genet 8:762–775PubMedCrossRefGoogle Scholar
  21. Clay O, Douady CJ, Carels N, Hughes S, Bucciarelli G, Bernardi G (2003) Using analytical ultracentrifugation to study compositional variation in vertebrate genomes. Eur Biophys J 32:418–426PubMedCrossRefGoogle Scholar
  22. Cortadas J, Macaya G, Bernardi G (1977) An analysis of the bovine genome by density gradient centrifugation: fractionation in Cs2SO4/3,6-bis(acetatomercurimethyl)dioxane density gradient. Eur J Biochem 76:13–19PubMedCrossRefGoogle Scholar
  23. Costantini M, Auletta F, Bernardi G (2007) Isochore patterns and gene distributions in fish genomes. Genomics 90:364–371PubMedCrossRefGoogle Scholar
  24. Costantini M, Cammarano R, Bernardi G (2009) The evolution of isochore patterns in vertebrate genomes. BMC Genomics 10:146PubMedPubMedCentralCrossRefGoogle Scholar
  25. Cuny G, Soriano P, Macaya G, Bernardi G (1981) The major components of the mouse and human genomes. 1. Preparation, basic properties and compositional heterogeneity. Eur J Biochem 115:227–233PubMedCrossRefGoogle Scholar
  26. Davis BK (1998) The forces driving molecular evolution. Prog Biophys Mol Biol 69:83–150PubMedCrossRefGoogle Scholar
  27. Dean AM (2010) The future of molecular evolution. EMBO Rep 11:409PubMedPubMedCentralCrossRefGoogle Scholar
  28. Dietrich MR (1994) The origins of the neutral theory of molecular evolution. J Hist Biol 27:21–59PubMedCrossRefGoogle Scholar
  29. Dokoumetzidis A, Iliadis A, Macheras P (2001) Nonlinear dynamics and chaos theory: concepts and applications relevant to pharmacodynamics. Pharm Res 18:415–426PubMedCrossRefGoogle Scholar
  30. Donatsch P, Gurtler J, Matter BE (1982) Critical appraisal of the ‘mouse testicular DNA-synthesis inhibition test’ for the detection of mutagens and carcinogens. Mutat Res 92:265–273PubMedCrossRefGoogle Scholar
  31. Duret L, Arndt PF (2008) The impact of recombination on nucleotide substitutions in the human genome. PLoS Genet 4:e1000071PubMedPubMedCentralCrossRefGoogle Scholar
  32. Duret L, Mouchiroud D, Gautier C (1995) Statistical analysis of vertebrate sequences reveals that long genes are scarce in GC-rich isochores. J Mol Evol 40:308–317PubMedCrossRefGoogle Scholar
  33. Duret L, Semon M, Piganeau G, Mouchiroud D, Galtier N (2002) Vanishing GC-rich isochores in mammalian genomes. Genetics 162:1837–1847PubMedPubMedCentralGoogle Scholar
  34. Elena SF, Lenski RE (2003) Evolution experiments with microorganisms: the dynamics and genetic bases of adaptation. Nat Rev Genet 4:457–469PubMedCrossRefGoogle Scholar
  35. Engelhardt BE, Jordan MI, Srouji JR, Brenner SE (2011) Genome-scale phylogenetic function annotation of large and diverse protein families. Genome Res 21:1969–1980PubMedPubMedCentralCrossRefGoogle Scholar
  36. Eyre-Walker A (1993) Recombination and mammalian genome evolution. Proc Biol Sci 252:237–243PubMedCrossRefGoogle Scholar
  37. Eyre-Walker A, Hurst LD (2001) The evolution of isochores. Nat Rev Genet 2:549–555PubMedCrossRefGoogle Scholar
  38. Felsenstein J (1981) Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol 17:368–376PubMedCrossRefGoogle Scholar
  39. Fryxell KJ, Moon WJ (2005) CpG mutation rates in the human genome are highly dependent on local GC content. Mol Biol Evol 22:650–658PubMedCrossRefGoogle Scholar
  40. Fryxell KJ, Zuckerkandl E (2000) Cytosine deamination plays a primary role in the evolution of mammalian isochores. Mol Biol Evol 17:1371–1383PubMedCrossRefGoogle Scholar
  41. Fudenberg D, Levine DK (1988) Open-loop and closed-loop equilibria in dynamic games with many players. J Econ Theory 44:1–18CrossRefGoogle Scholar
  42. Fujita MK, Edwards SV, Ponting CP (2011) The Anolis lizard genome: an amniote genome without isochores. Genome Biol Evol 3:974–984PubMedPubMedCentralCrossRefGoogle Scholar
  43. Galtier N, Piganeau G, Mouchiroud D, Duret L (2001) GC-content evolution in mammalian genomes: the biased gene conversion hypothesis. Genetics 159:907–911PubMedPubMedCentralGoogle Scholar
  44. Garcia P, Velasco M (2013) Exploratory strategies: experiments and simulations. In: Duran JM, Eckhart A (eds) Computer simulations and the changing face of scientific experimentation. Cambridge Scholars Publishing, CambridgeGoogle Scholar
  45. Gascuel O, Bryant D, Denis F (2001) Strengths and limitations of the minimum evolution principle. Syst Biol 50:621–627PubMedCrossRefGoogle Scholar
  46. Gilbert W, Maxam A (1973) The nucleotide sequence of the lac operator. Proc Natl Acad Sci U S A 70:3581–3584PubMedPubMedCentralCrossRefGoogle Scholar
  47. Gingerich PD (1986) Temporal scaling of molecular evolution in primates and other mammals. Mol Biol Evol 3:205–221PubMedGoogle Scholar
  48. Giribet G (2003) Molecules, development and fossils in the study of metazoan evolution; Articulata versus Ecdysozoa revisited. Zoology (Jena) 106:303–326Google Scholar
  49. Green RE, Krause J, Ptak SE, Briggs AW, Ronan MT, Simons JF, Du L, Egholm M, Rothberg JM, Paunovic M et al (2006) Analysis of one million base pairs of Neanderthal DNA. Nature 444:330–336PubMedCrossRefGoogle Scholar
  50. Greene CS, Tan J, Ung M, Moore JH, Cheng C (2014) Big data bioinformatics. J Cell Physiol 229:1896–1900PubMedPubMedCentralCrossRefGoogle Scholar
  51. Gu X, Li WH (1998) Estimation of evolutionary distances under stationary and nonstationary models of nucleotide substitution. Proc Natl Acad Sci U S A 95:5899–5905PubMedPubMedCentralCrossRefGoogle Scholar
  52. Gu J, Li WH (2006) Are GC-rich isochores vanishing in mammals? Gene 385:50–56PubMedCrossRefGoogle Scholar
  53. Guagliardi A, Napoli A, Rossi M, Ciaramella M (1997) Annealing of complementary DNA strands above the melting point of the duplex promoted by an archaeal protein. J Mol Biol 267:841–848PubMedCrossRefGoogle Scholar
  54. Haiminen N, Mannila H (2007) Discovering isochores by least-squares optimal segmentation. Gene 394:53–60PubMedCrossRefGoogle Scholar
  55. Hamada K, Horiike T, Ota H, Mizuno K, Shinozawa T (2003) Presence of isochore structures in reptile genomes suggested by the relationship between GC contents of intron regions and those of coding regions. Genes Genet Syst 78:195–198PubMedCrossRefGoogle Scholar
  56. Hedges SB, Dudley J, Kumar S (2006) TimeTree: a public knowledge-base of divergence times among organisms. Bioinformatics 22:2971–2972PubMedCrossRefGoogle Scholar
  57. Hipsley CA, Muller J (2014) Beyond fossil calibrations: realities of molecular clock practices in evolutionary biology. Front Genet 5:138PubMedPubMedCentralCrossRefGoogle Scholar
  58. Holmquist GP (1989) Evolution of chromosome bands: molecular ecology of noncoding DNA. J Mol Evol 28:469–486PubMedCrossRefGoogle Scholar
  59. Huang W, Nevins JR, Ohler U (2007) Phylogenetic simulation of promoter evolution: estimation and modeling of binding site turnover events and assessment of their impact on alignment tools. Genome Biol 8:R225PubMedPubMedCentralCrossRefGoogle Scholar
  60. Kaehler BD, Yap VB, Zhang R, Huttley GA (2014) Genetic distance for a general non-stationary Markov substitution process. Syst Biol 64:281–293Google Scholar
  61. Karolchik D, Baertsch R, Diekhans M, Furey TS, Hinrichs A, Lu YT, Roskin KM, Schwartz M, Sugnet CW, Thomas DJ et al (2003) The UCSC genome browser database. Nucleic Acids Res 31:51–54PubMedPubMedCentralCrossRefGoogle Scholar
  62. Karro JE, Peifer M, Hardison RC, Kollmann M, von Grünberg HH (2008) Exponential decay of GC content detected by strand-symmetric substitution rates influences the evolution of isochore structure. Mol Biol Evol 25:362–374PubMedCrossRefGoogle Scholar
  63. Kell DB, Lurie-Luke E (2015) The virtue of innovation: innovation through the lenses of biological evolution. J R Soc Interface 12Google Scholar
  64. Kimura M (1968) Evolutionary rate at the molecular level. Nature 217:624–626PubMedCrossRefGoogle Scholar
  65. Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, CambridgeGoogle Scholar
  66. King MT, Wild D (1983) The mutagenic potential of hyperthermia and fever in mice. Mutat Res 111:219–226PubMedCrossRefGoogle Scholar
  67. Kirchner JW, Weil A (2000) Correlations in fossil extinction and origination rates through geological time. Proc Biol Sci 267:1301–1309PubMedPubMedCentralCrossRefGoogle Scholar
  68. Komiya K, Kondoh T, Aotsuka T (1995) Evolution of the noncoding regions in Drosophila mitochondrial DNA: two intergenic regions. Biochem Genet 33:73–82PubMedCrossRefGoogle Scholar
  69. Koonin EV (2007) The cosmological model of eternal inflation and the transition from chance to biological evolution in the history of life. Biol Direct 2:15PubMedPubMedCentralCrossRefGoogle Scholar
  70. Koonin EV (2009) Darwinian evolution in the light of genomics. Nucleic Acids Res 37:1011–1034PubMedPubMedCentralCrossRefGoogle Scholar
  71. Kopp M, Matuszewski S (2014) Rapid evolution of quantitative traits: theoretical perspectives. Evol Appl 7:169–191PubMedCrossRefGoogle Scholar
  72. Kosiol C, Goldman N (2011) Markovian and non-Markovian protein sequence evolution: aggregated Markov process models. J Mol Biol 411:910–923PubMedPubMedCentralCrossRefGoogle Scholar
  73. Kvikstad EM, Duret L (2014) Strong heterogeneity in mutation rate causes misleading hallmarks of natural selection on indel mutations in the human genome. Mol Biol Evol 31:23–36PubMedCrossRefGoogle Scholar
  74. Lesecque Y, Mouchiroud D, Duret L (2013) GC-biased gene conversion in yeast is specifically associated with crossovers: molecular mechanisms and evolutionary significance. Mol Biol Evol 30:1409–1419PubMedPubMedCentralCrossRefGoogle Scholar
  75. Li W (2002) Are isochore sequences homogeneous? Gene 300:129–139PubMedCrossRefGoogle Scholar
  76. Liberles DA (2001) Evolution enters the genomic era. Genome Biol 2:REPORTS4026Google Scholar
  77. Lio P, Goldman N (1998) Models of molecular evolution and phylogeny. Genome Res 8:1233–1244PubMedCrossRefGoogle Scholar
  78. Macaya G, Cortadas J, Bernardi G (1978) An analysis of the bovine genome by density-gradient centrifugation. Preparation of the dG+dC-rich DNA components. Eur J Biochem 84:179–188PubMedCrossRefGoogle Scholar
  79. Majoros WH, Ohler U (2010) Modeling the evolution of regulatory elements by simultaneous detection and alignment with phylogenetic pair HMMs. PLoS Comput Biol 6:e1001037PubMedPubMedCentralCrossRefGoogle Scholar
  80. Mandel M, Marmur J, Lawrence Grossman KM (1968) [109] Use of ultraviolet absorbance-temperature profile for determining the guanine plus cytosine content of DNA. In: Nucleic acids, Part B. Academic, New York, pp 195–206Google Scholar
  81. Maxam AM, Gilbert W (1977) A new method for sequencing DNA. Proc Natl Acad Sci U S A 74:560–564PubMedPubMedCentralCrossRefGoogle Scholar
  82. Mayr E (2004) What makes biology unique?: Considerations on the autonomy of a scientific discipline. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  83. Mazzocchi F (2008) Complexity in biology. Exceeding the limits of reductionism and determinism using complexity theory. EMBO Rep 9:10–14PubMedPubMedCentralCrossRefGoogle Scholar
  84. McDonald JH (2001) Patterns of temperature adaptation in proteins from the bacteria Deinococcus radiodurans and Thermus thermophilus. Mol Biol Evol 18:741–749PubMedCrossRefGoogle Scholar
  85. Melodelima C, Gautier C (2008) The GC-heterogeneity of teleost fishes. BMC Genomics 9:632PubMedPubMedCentralCrossRefGoogle Scholar
  86. Mikkelsen TS, Wakefield MJ, Aken B, Amemiya CT, Chang JL, Duke S, Garber M, Gentles AJ, Goodstadt L, Heger A et al (2007) Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. Nature 447:167–177PubMedCrossRefGoogle Scholar
  87. Mir K, Schober S (2014) Selection pressure in alternative reading frames. PLoS One 9:e108768PubMedPubMedCentralCrossRefGoogle Scholar
  88. Montoya-Burgos JI, Boursot P, Galtier N (2003) Recombination explains isochores in mammalian genomes. Trends Genet 19:128–130PubMedCrossRefGoogle Scholar
  89. Moses A, Chiang D, Kellis M, Lander E, Eisen M (2003) Position specific variation in the rate of evolution in transcription factor binding sites. BMC Evol Biol 3:19PubMedPubMedCentralCrossRefGoogle Scholar
  90. Nachman MW, Crowell SL (2000) Estimate of the mutation rate per nucleotide in humans. Genetics 156:297–304PubMedPubMedCentralGoogle Scholar
  91. Nei M (2005) Selectionism and neutralism in molecular evolution. Mol Biol Evol 22:2318–2342PubMedPubMedCentralCrossRefGoogle Scholar
  92. Nei M (2013) Mutation-driven evolution. Oxford University Press, OxfordGoogle Scholar
  93. Nekrutenko A, Li WH (2000) Assessment of compositional heterogeneity within and between eukaryotic genomes. Genome Res 10:1986–1995PubMedPubMedCentralCrossRefGoogle Scholar
  94. Norell MA, Novacek MJ (1992) The fossil record and evolution: comparing cladistic and paleontologic evidence for vertebrate history. Science 255:1690–1693PubMedCrossRefGoogle Scholar
  95. Oestreicher C (2007) A history of chaos theory. Dialogues Clin Neurosci 9:279–289PubMedPubMedCentralGoogle Scholar
  96. O’Higgins P (2000) The study of morphological variation in the hominid fossil record: biology, landmarks and geometry. J Anat 197(1):103–120Google Scholar
  97. Ohno S (1972) So much “junk” DNA in our genome. Brookhaven Symp Biol 23:366–370PubMedGoogle Scholar
  98. Ohno S, Yomo T (1991) The grammatical rule for all DNA: junk and coding sequences. Electrophoresis 12:103–108PubMedCrossRefGoogle Scholar
  99. Oota S, Kawamura K, Kawai Y, Saitou N (2010) A new framework for studying the isochore evolution: estimation of the equilibrium GC content based on the temporal mutation rate model. Genome Biol Evol 2:558–571PubMedPubMedCentralCrossRefGoogle Scholar
  100. Oreskes N, Shrader-Frechette K, Belitz K (1994) Verification, validation, and confirmation of numerical models in the earth sciences. Science 263:641–646PubMedCrossRefGoogle Scholar
  101. Orzack SH (2012) The philosophy of modelling or does the philosophy of biology have any use? Philos Trans R Soc Lond Ser B Biol Sci 367:170–180CrossRefGoogle Scholar
  102. Papp B, Notebaart RA, Pal C (2011) Systems-biology approaches for predicting genomic evolution. Nat Rev Genet 12:591–602PubMedCrossRefGoogle Scholar
  103. Pavlicek A, Clay O, Jabbari K, Paces J, Bernardi G (2002) Isochore conservation between MHC regions on human chromosome 6 and mouse chromosome 17. FEBS Lett 511:175–177PubMedCrossRefGoogle Scholar
  104. Pessia E, Popa A, Mousset S, Rezvoy C, Duret L, Marais GA (2012) Evidence for widespread GC-biased gene conversion in eukaryotes. Genome Biol Evol 4:675–682PubMedPubMedCentralCrossRefGoogle Scholar
  105. Phear G, Meuth M (1989) The genetic consequences of DNA precursor pool imbalance: sequence analysis of mutations induced by excess thymidine at the hamster aprt locus. Mutat Res 214:201–206PubMedCrossRefGoogle Scholar
  106. Popper KR, Eccles JC (1984) The self and its brain, Reprint edition. RoutledgeGoogle Scholar
  107. Rabinovich MI, Abarbanel HD (1998) The role of chaos in neural systems. Neuroscience 87:5–14PubMedCrossRefGoogle Scholar
  108. Rodriguez-Trelles F, Tarrio R, Ayala FJ (2002) A methodological bias toward overestimation of molecular evolutionary time scales. Proc Natl Acad Sci U S A 99:8112–8115PubMedPubMedCentralCrossRefGoogle Scholar
  109. Rzhetsky A, Nei M (1993) Theoretical foundation of the minimum-evolution method of phylogenetic inference. Mol Biol Evol 10:1073–1095PubMedGoogle Scholar
  110. Sanger F, Coulson AR (1975) A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol 94:441–448PubMedCrossRefGoogle Scholar
  111. Sanger F, Donelson JE, Coulson AR, Kossel H, Fischer D (1973) Use of DNA polymerase I primed by a synthetic oligonucleotide to determine a nucleotide sequence in phage fl DNA. Proc Natl Acad Sci U S A 70:1209–1213PubMedPubMedCentralCrossRefGoogle Scholar
  112. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 74:5463–5467PubMedPubMedCentralCrossRefGoogle Scholar
  113. Sawyer SA, Hartl DL (1992) Population genetics of polymorphism and divergence. Genetics 132:1161–1176PubMedPubMedCentralGoogle Scholar
  114. Schneider D, Duperchy E, Coursange E, Lenski RE, Blot M (2000) Long-term experimental evolution in Escherichia coli. IX Characterization of insertion sequence-mediated mutations and rearrangements. Genetics 156:477–488PubMedPubMedCentralGoogle Scholar
  115. Scientists GKCo (2009) Genome 10K: a proposal to obtain whole-genome sequence for 10 000 vertebrate species. J Hered 100:659–674CrossRefGoogle Scholar
  116. Siegel MJ (1976) The asymptotic behavior of a divergent linear birth and death process. Adv Appl Probab 8:315–338CrossRefGoogle Scholar
  117. Smith TF (1980) Occam’s razor. Nature 285:620PubMedCrossRefGoogle Scholar
  118. Smith NG, Webster MT, Ellegren H (2002) Deterministic mutation rate variation in the human genome. Genome Res 12:1350–1356PubMedPubMedCentralCrossRefGoogle Scholar
  119. Smyrlis YS, Papageorgiou DT (1991) Predicting chaos for infinite dimensional dynamical systems: the Kuramoto-Sivashinsky equation, a case study. Proc Natl Acad Sci U S A 88:11129–11132PubMedPubMedCentralCrossRefGoogle Scholar
  120. Song S, Jarvie T, Hattori M (2013) Our second genome-human metagenome: how next-generation sequencer changes our life through microbiology. Adv Microb Physiol 62:119–144PubMedCrossRefGoogle Scholar
  121. Stamatoyannopoulos JA, Adzhubei I, Thurman RE, Kryukov GV, Mirkin SM, Sunyaev SR (2009) Human mutation rate associated with DNA replication timing. Nat Genet 41:393–395PubMedPubMedCentralCrossRefGoogle Scholar
  122. Stephens R, Horton R, Humphray S, Rowen L, Trowsdale J, Beck S (1999) Gene organisation, sequence variation and isochore structure at the centromeric boundary of the human MHC. J Mol Biol 291:789–799PubMedCrossRefGoogle Scholar
  123. Strizhak PE, Pojman JA (1996) Infinite period and Hopf bifurcations for the pH-regulated oscillations in a semibatch reactor (H(2)O(2)-Cu(2+)-S(2)O(2-) (3)-NaOH system). Chaos 6:461–465PubMedCrossRefGoogle Scholar
  124. Subramanian S, Lambert DM (2011) Time dependency of molecular evolutionary rates? Yes and no. Genome Biol Evol 3:1324–1328PubMedPubMedCentralCrossRefGoogle Scholar
  125. Sueoka N (1961) Correlation between base composition of deoxyribonucleic acid and amino acid composition of protein. Proc Natl Acad Sci U S A 47:1141–1149PubMedPubMedCentralCrossRefGoogle Scholar
  126. Sueoka N (1962) On the genetic basis of variation and heterogeneity of DNA base composition. Proc Natl Acad Sci U S A 48:582–592PubMedPubMedCentralCrossRefGoogle Scholar
  127. Sueoka N (1988) Directional mutation pressure and neutral molecular evolution. Proc Natl Acad Sci 85:2653–2657PubMedPubMedCentralCrossRefGoogle Scholar
  128. Sueoka N, Marmur J, Doty P (1959) Heterogeneity in deoxyribonucleic acids: II. Dependence of the density of deoxyribonucleic acids on guanine-cytosine content. Nature 183:1429–1431PubMedCrossRefGoogle Scholar
  129. Takahata N (2007) Molecular clock: an anti-neo-Darwinian legacy. Genetics 176:1–6PubMedPubMedCentralCrossRefGoogle Scholar
  130. Tikchonenko TI, Dubichev AG, Lyubchenko Yu L, Kvitko NP, Chaplygina NM, Kalinina TI, Dreizin RS, Naroditsky BS (1981) The distribution of guanine-cytosine pairs in adenovirus DNAs. J Gen Virol 54:425–429PubMedCrossRefGoogle Scholar
  131. Van Regenmortel MH (2004) Reductionism and complexity in molecular biology. Scientists now have the tools to unravel biological and overcome the limitations of reductionism. EMBO Rep 5:1016–1020PubMedPubMedCentralCrossRefGoogle Scholar
  132. Verbyla KL, Yap VB, Pahwa A, Shao Y, Huttley GA (2013) The embedding problem for markov models of nucleotide substitution. PLoS One 8:e69187PubMedPubMedCentralCrossRefGoogle Scholar
  133. Vinogradov AE (2003a) DNA helix: the importance of being GC-rich. Nucleic Acids Res 31:1838–1844PubMedPubMedCentralCrossRefGoogle Scholar
  134. Vinogradov AE (2003b) Isochores and tissue-specificity. Nucleic Acids Res 31:5212–5220PubMedPubMedCentralCrossRefGoogle Scholar
  135. Walser JC, Ponger L, Furano AV (2008) CpG dinucleotides and the mutation rate of non-CpG DNA. Genome Res 18:1403–1414PubMedPubMedCentralCrossRefGoogle Scholar
  136. Warren WC, Hillier LW, Marshall Graves JA, Birney E, Ponting CP, Grutzner F, Belov K, Miller W, Clarke L, Chinwalla AT et al (2008) Genome analysis of the platypus reveals unique signatures of evolution. Nature 453:175–183PubMedPubMedCentralCrossRefGoogle Scholar
  137. Webster MT, Smith NG, Ellegren H (2003) Compositional evolution of noncoding DNA in the human and chimpanzee genomes. Mol Biol Evol 20:278–286PubMedCrossRefGoogle Scholar
  138. Wolfe KH, Sharp PM, Li WH (1989) Mutation rates differ among regions of the mammalian genome. Nature 337:283–285PubMedCrossRefGoogle Scholar
  139. Wood RE, Barroso-Ruiz C, Caparros M, Jorda Pardo JF, Galvan Santos B, Higham TF (2013) Radiocarbon dating casts doubt on the late chronology of the Middle to Upper Palaeolithic transition in southern Iberia. Proc Natl Acad Sci U S A 110:2781–2786PubMedPubMedCentralCrossRefGoogle Scholar
  140. Wu H, Zhang Z, Hu S, Yu J (2012) On the molecular mechanism of GC content variation among eubacterial genomes. Biol Direct 7:2PubMedPubMedCentralCrossRefGoogle Scholar
  141. Yakovchuk P, Protozanova E, Frank-Kamenetskii MD (2006) Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Res 34:564–574PubMedPubMedCentralCrossRefGoogle Scholar
  142. Zhaxybayeva O, Nesbo CL, Doolittle WF (2007) Systematic overestimation of gene gain through false diagnosis of gene absence. Genome Biol 8:402PubMedPubMedCentralCrossRefGoogle Scholar
  143. Zuckerkandl E (1987) On the molecular evolutionary clock. J Mol Evol 26:34–46PubMedCrossRefGoogle Scholar
  144. Zuckerkandl E (2012) Fifty-year old and still ticking.... an interview with Emile Zuckerkandl on the 50th anniversary of the molecular clock. Interview by Giacomo Bernardi. J Mol Evol 74:233–236PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan KK 2017

Authors and Affiliations

  1. 1.RIKEN Bioresource CenterTsukubaJapan

Personalised recommendations