ORIGIN OF GENOMIC DNA: DISCUSSION FROM REVERSE-TRANSCRIPTION AND EXPANSION OF
REPETITIVE OLIGONUCLEOTIDES
Takanori Miura
Taiko Pharmaceutical Co., Ltd., Uchihonmachi 3-34-14 Suita Osaka 564-0032 JAPANTEL +81-6-6382-1023, FAX +81-6-6382-3084
E-mail: takanori@myrealbox.com(Received 25 October, 2002

Accepted 3 February 2003)(Abstract)

Genetic information of organisms is preserved within sequences of nucleotides in genomic DNAs, which are possible
to be replicated by DNA polymerase semiconservatively. The sequences of the DNA molecules in organisms arevariant, but long. Even the DNA of Mycoplasma genitalium, which has a smallest DNA among all types of organisms,
is of 580-kilobase pairs in length. However, the long DNA can be synthesized with neither some prebiotic experiments
nor the present DNA synthesizing techniques. Only oligoribonucleotides 55mer are possible to be synthesized in thepresence of a montmollironite clay under prebiotic conditions. How is the long DNA synthesized in the primordial
environment? Ohno proposed the model that genes of the present organisms emerged from short repetitive
oligoribonucleotides. Several types of DNA polymerase are capable to synthesize long repetitive DNAs with more than
50-kilobase pairs in length from short oligonucleotides such as (TA)n, (TG)n, (CAG)n, (TAGG) n, (TTAGGG)n,(TACATGTA)n, and (AGATATCT)n by conventional enzymatic reactions. Furthermore, telomerase, which catalyzes
the synthesis of the telomere of eucaryotic genome ends, can synthesize the complementary repetitive DNA(TTGGGG)n in the presence of a RNA template by the reverse-transcriptional activity. There are various repetitive
sequences such as (GT)n, (CAG)n, (GGAAT)n, and (TTAGGC)n in the genomic DNA of different organisms containing
Bacteria and Eucarya. Based on these examples, it is deduced that short repetitive DNA should have been synthesizedfrom short RNA in the presence of oligopeptides catalysts or ribozymes, which have primordial reverse transcriptaselike activity; genomic DNA should have emerged from long repetitive DNAs elongated from the short repetitive DNA
in the presence of primordial DNA polymerase-like oligopeptides or ribozymes. I discuss the plausibility of these ideas,
proposing a model for the origin of genomic DNA from the reverse-transcription and expansion of repetitive
oligonucleotides.

(Keyword)
repetitive oligonucleotide, tandem repeat, DNA polymerase, telomerase, genomic DNA, DNA elongation
chemical evolution of DNA

Viva Origino 31 (2003) 46-61©2003 by SSOEL Japan46

Viva Origino 31 (2003) 46- 61

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Viva Origino 31 (2003) 46- 61
Table 1. Typical genome sizes and gene amounts of some organisms
Spiecesgenome size

gene number

Bacteria
Mycoplasma genitalium
Buchnera sp.
Escherichia coli K12
Bacillus sabtilis
Pseudomonas aeruginosa
Synecocystis sp. PCC6803

580 kb640 kb
4.64 Mb
4.21 Mb
6.3 Mb
3.57 Mb

484
564
4289
4100
5565
3169

Archaea
Methanococcus jannaschii
Pyrococcus harikoshii
Aeropyrum pernix
Halobacterium sp.

1.66 Mb
1.74 Mb
1.67 Mb
2 Mb

1715
1979
2694
2058

Eucarya
Saccharomyces cerevisiae
Caenorhabditis elegans
Drosophila melanogasterArabidopsis thaliana
Homo sapiens

12 Mb
97 Mb
120 Mb125 Mb
3 Gb

6286
18000
13000
25498
30000

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48

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Viva Origino 31 (2003) 46- 61
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50

Viva Origino 31 (2003) 46- 61
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GåB?>æçè;éxêBCDSnuÊF;ÃÄY¢f[13]Uv DNA B>ÊCDSnSxFv

vvFµ¶>GÃÄ?>FP?BCDSn

áp>nES DNA x4v;ÐëBCU

S³2xT;fTUf£F(1)¨©kq3

VÖ Khorana dL_>F(TG)2-6/(AC)2-6 [44]FP IXxopeTF(2)´Õhi(TAG)4/(TAC)3-4 [45]FTS>(TATC)3/(TAGA)2 [46]}ÇIY45P?opeTF(3)Ø

n= 2F3F4 hiöÃnTxF

Ùu xnSFn=xVCeTUnFÚ DNA HIJKLM?uD[TG;YÊGÄ>67 |4;Sm)3e RNA ;cÜÝUGC tHI¬_;fCDSTU

ÞYi.;vÖ×¾RNAacÜÝÞûLÀenFv DNA B>F (TA)>ØU[TxF2o DNA  RNA ;cÜÝ (TA)ÞÖ×¾DNAaRNAacÜÝÞûLÀ?

nSU

DNA 

DNA F;ÚÛ?ìBCDS

1992 Ï? Schlötterer ; Tautz >F2 hi 3 h

T  DNA |4>vDSnSUVGe}Ö.e>F!ÃÄY~¡;vD RNAacÜÝ

iÞûL DNAaRNAacÜÝÞûL¬_[TG;YJ§LHæçè;ée 1¤ÙÚ  DNA |4?½SD

vFW 700 hijye[TG;Yv[47]U51

öÃYZ[T³Ûn

DNA xF37°C eHI

Viva Origino 31 (2003) 46- 61
Table 2. Summary of repetitive DNA elongation with some DNA polymerase
Short DNA sequence(5'-> 3')

Reaction
temperature

DNA lenght
elongation

DNA polymerase

Reference()

before
(bp)

after
(bp)

(TA)3-7

0-45

6-14

ND

E. coli pol I

42(TG)2-6/(CA)2-6

37

4-12

ND

E. coli pol I

44(TTC)3-4/(AAG)3-5(TAC)3/(TAG)4-5(TAG)4/(TAC)3-4(ATG)3/(ATC)3-5

37
37
37
37

9-15
9-15
9-15
9-15

ND
ND
ND
ND

E. coli pol I
E. coli pol I
E. coli pol I
E. coli pol I

45
45
45
45

(TATC)3/(TAGA)2(TAAG)2/(TTAC)3-4

37
37

8-12
8-16

ND
ND

E. coli pol I
E. coli pol I

4646(GT)15/(CA)9(AG)15/(TC)9(ATT)15/(AAT)9(GTT)15/(ACA)9(TCT)15/(AGA)9(TCA)15/(ATG)9(TAC)15/(TAG)9(TCC)15/(GGA)9(CCA)15/(GGT)9(TCG)15/(ACG)9(TGC)15/(GCA)9

37
37
37
37
37
37
37
37
37
37
37

18, 3018, 3027, 4527, 4527, 4527, 4527, 4527, 4527, 4527, 4527, 45

460
700
400
120
250
110
350
200
100
50
50

E. coli pol I
E. coli pol I
E. coli pol I
E. coli pol I
E. coli pol I
E. coli pol I
E. coli pol I
E. coli pol I
E. coli pol I
E. coli pol I
E. coli pol I

47
47
47
47
47
47
47
47
47
47
47

(GCC)5/(GCC)5(GCC)5/(GCC)5(GCC)5/(GCC)5(GCC)5/(GCC)5(GCC)5/(GCC)5(GCC)5/(GCC)5

37
37
37
37
37
37

15
15
15
15
15
15

250
80
32
45
30
40

Taq pol
Klenow
Sequenase
HIV-RT
Calf pol α
mouse pol β

48
48
48
48
48
48

(AT)8
(TA)9

65
65

16
18

20000
20000

Taq pol
Taq pol

49
49(AAT)3/(ATT)5(AAT)3/(ATT)5(CAG)3/(CTG)5

47
47
47

9, 15
9, 15
9, 15

20000
2200
2000

Klenow
Taq pol
Taq pol

50
50
50(TACATGTA)6(TACATGTT)6(TACATGAA)6(TACATCTA)6(TACAAGTA)6(TACATGAT)6(TACATCAT)6(TACAACAT)6(AGGTACCT)6

74
74
74
74
74
74
74
74
74

48
48
48
48
48
48
48
48
48

10000
ND
ND
ND
10000
ND
ND
ND
10000

Tth polTth polTth polTth polTth polTth polTth polTth polTth pol

52
52
52
52
52
52
52
52
52

(AGATATCT)3(AT)24(AGGTACCT)6(TGATATCA)6(ACATATGT)6(TCATATGA)6(ACTTAAGT)6(TATTAAGA)6(AAAGCTTT)6(TCTATAGA)6(TACATGTA)6(AACATGTT)6(TTCATGAA)6(TAGATCTA)6(TACTAGTA)6(TAAGCTTA)6(TATGCATA)6(AGATATCA)6(AGATTTCT)6(AGGGCCCT)6(GC)24

74
74
74
74
74
74
74
74
74
74
74
74
74
74
74
74
74
74
74
74
74

24
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48

20000
ND
ND
ND
ND
ND
20000
ND
20000
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND

Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol
Tli pol

53
53
53
53
53
53
53
53
53
53
53
53
53
53
53
53
53
53
53
53
53

(TAGG)10/(CCTA)10(TTAAGGGG)5/(CCCCTTAA)5(TTAGGG)5/(CCCTAA)5(TTGGAG)5/(CTCCAA)5(TGTGAG)5/(CTCACA)5(ACGTCA)5/(TGACGT)5

70
75
75
75
75
75

40
40
30
30
30
30

10000
10000
10000
10000
10000
10000

Taq pol
Taq pol
Taq pol
Taq pol
Taq pol
Taq pol

54
54
54
54
54
54

ND: Not determine, bp: base pair
E. coli pol I: Escherichia coli DNA polymerase I, Taq pol: Thermus aquaticus DNA polymerase,
Klenow: Klenow fragment of E. coli pol I, Sequenase: modified T7 DNA polymerase,
HIV-RT: HIV reverse transcriptase, Calf pol α: Calf thymus DNA polymerase α,
mouse pol β: mouse DNA polymerase β, Tth pol: Thermus thermophilus DNA polymerase,
Tli pol: Thermococcus litoralis DNA polymerase

52Viva Origino 31 (2003) 46- 61ab  
melting+annealingc

 

replication

hairpin formation(  


 

replication

slippage)

  
melting+annealing



( 


replication

replication 



)


slippage

( 

replication slippagebulge migration

replication


 









( 
large DNA

d




   











   















  
 
 



replication










large DNA




   



meltingannealing

meltingannealing

replication



    





 

     


 





’ 


 





     





 
     


 
 


 
 

 



Figure 1. Several models for the repetitive DNA elongation by DNA polymerases(a) Standard DNA replication mechanism: DNA duplex is melted, and then each single stranded DNA (ssDNA) is annealed with each primer
DNA. Complementary DNA is replicated from 3'-OH end of the primer DNA. (b) DNA slippage synthesis model: Newly synthesized stretchof repetitive (TA) DNA is replicated with template (TA) ssDNA. The newly synthesized DNA is "slipped" to the direction of the 3'-OH end of
the template. Newly generated ssDNA is replicated by DNA polymerase. Next slippage synthesis goes on until large DNA is made. (c) Hairpin
elongation model: Short palindrome repetitive DNA forms a hairpin structure by folding back, and then its end melt partially. The 3'-end arm of
the hairpin locally forms a small hairpin, and DNA polymerase elongates the DNA from the 3'-OH end. The small hairpin is next incorporated
into the large hairpin by slippage. These cycles of hairpin formation, elongation and slippage are repeated until large DNA is made. (d)Template switching and strand displacement model: Fraying at the ends of duplexes can occur. Due to end fraying, there is transitionintermolecular base pairing between duplexes in solution. The strand-displacement activity of the polymerase is then responsible for extending
the complementary strands of the DNA duplexes in these intermolecular complexes (Left). At reaction temperatures near the melting point of
the duplex, repeated melting and staggered reannealing leads to more efficient extension of the two DNA strands (Right). As the DNA increases
in length, bulges form in the duplex at elevated temperature. SsDNA in bulged regions serves as templates for the extension of other duplexes.

53

Viva Origino 31 (2003) 46- 61
nF PCR ?U[T Taq DNA HIJKLMYUS(TTAAGGGG)5/(CCCCTTAA)5 n= 2 . Y«[DtFDNA xHI¬_e[TG;T DNA eF÷JÝÜ§>FZ[e>«vn

t@=vDSTUG Taq DNA HIJKLM?T

SG;xìBCUnFKlenow ÁÂet 37°C e



GC

DNA 

DNA ¤>FE. coli DNA

DNA xÍ 100 hijye[TG;tHIJKLM I ;;t?FQ´dL_x 1Y

ÊCDSTUüýþ Y 1v

Gnu[48,49,50]UVCCFTaq DNA HIJKL;GFHI¬_z÷JÝÜ;>ânEF¨

M; Klenow ÁÂ[51]YUSDF(AT)8 ;(AAT)3/(ATT)5© DNA E±f(template switching)[55];°w±f;Sm 16  9 hi(strand displacement)[56]YUvD[TG;xhijYàfTDNA xF
VCC 20000

DNA yevU

VÖíò>FBC(Fig. 1d)UG9¬>FÛFÜ-eöÃx 4 hi}Ç ?SDF2o DNA ²e

DNA ;vD 2 è! DNA HIJKLM?
uD 8 hiöÃY¼½

DNA x

DNA

gõ?L[T(unequal crossingover)[57]; .P?!"v¨© DNA E±f2

DNA¤;[TG;Y9¬v[52,53]UGCHIJKx)BCG;e!á

þSULM-ò>FTaq DNA HIJKLM;Úb}Ç9¬F

DNA Y$Õ%&;vDFîï»¯­® Thermus thermophilus öÌBCDNA HIJKLM>ÁÂI 

Tth DNA HIJKLMeFE. coli DNA HIJKLM I\LY:vFW 20000 hiY°±ðOILA ?b[TëìeTUnò>Fà;ewTG;xúuUvvFÁÂîï»Ò­® Thermococcus litoralis öÌBC Tli

I45P?½SD>F- 2 .

DNA HIJKLMeF¯ ­ñ DNA YQRet CxnEnmeT[17]U45P[T pol αY°±ðOILΒ?b[TëìeTUv?P?ewTI;V:xuDFHIJKLMc]_xânuDt#x$Õ%&;nEFÖ?BCÁÂI

DNA 

YUSD DNA xBCC£FDNA ¤xGTmeTU~¶VWe>F8 hiöÃ 6 ¥æEçv

45;

nT 48 hi¥ò

DNA (TACATGTA)6 xF

VGeR?F

74°C e 10000 hij(TACATGTA)n ye[TGDNA ¤DNA ;>myX½U
RNA 

DNA ¤ÛFÜ-

?LvD[U;xBC[52]UÖ¶e>FB?S 24 hi¯ 45>F DNA ÎÏ?

Y(AGATATCT)3 x Tli DNA HIJKLM?E 74°C e[T¦§JKLMY¼uDST[58]UGëì>Fc

20000 hij}Ç(AGATATCT)n ?[TG;xÜÝÞ:? RNA¾¦§JKLM RNAÀYZ[BC [53]Uñò;t?FTò

Y 1 hióvô¥ò

öÃ¥

etFDNA 

RNA ¦hi

Y¨©;vDUvFDNA ÎÏ?(TTGGGG)n z(TTAGGG)n n=

i>õö[Txx)BCDSTUnF(AGATATCT)3 z(TACATGTA)6 Y°±³ 8 hi¥òcÜÝÞ(ribonucleoprotein)eF¦§JKLMYP?:[TëìeT[59]UnF

DNA > 74°C e>÷JÝÜ§;KÜ^¦§JKLM>F4#-£EenÛFÜ-?S^]§²×Nø;nuDSTG;x¹ùùv»

DtF?Tï Ì» 1?uDBCUGGeFDNA YewTº»YZvDSTU
24 hi

ËúHI¬_ ;>ûm÷JÝÜ 

DNA Y 5200 hiye[TG;x;nu[59]U¦§JKLM>FöÃx 4F6F8 hinT 30 

40 hijk¥ò

RNA Y$Õ%&;vD

(TTGGGG)4 Y_K]\L;vDF¦§JKLMxFG

x¡¢BC(Fig. 1c)UWüF

DNA z

DNA xFTaq DNA HIJKL_K]\L;vDF} 20 hi

M?E 70°C e 10000 hij}Ç?[TG;xDNA(TTTATTTTTTATAAAAATTA)z 24 hiK

9 ¬ B C  [54] U   B þ  Ü ^ (TAGG)5/(CCTA)5

z

DNA >

(TTGGAG)5/(CTCCAA)5F

Y Z [ T DNA

(AGCCACTATCGACTACGGATCAT) YUSTG;x54

Viva Origino 31 (2003) 46- 61
ewF3'ÎÏ?(TTGGGG)n Y:vFÈ DNA Y

YZ[T\]^_K`\abcId(Mycoplasma[TG;tewT [60]U¦§JKLM_K]\L

genitalium)eBfF58 ghij;kl?S> F Ø l F DNA e  T x F r(GUUGGG)3   

DNA Y¼uDST[7](- 1 .)UGGye¥r(GGGUUG)3 

RNA Y_K]\L;vDUSF

YUSD45 DNA |4YfTÇe 2 ½¨© RNA Y DNA ¤ewT;Sm9¬tT

23xTUVC>FG2345 DNA[61]UGG;>F¦§JKLM

]²? DNA

B;

~45P e4ewT

x3ovnDtFRNA Y¨©;vDÁÂI

B?yE?t!wn¾¬_xT3;FDNA YewTº»YZ[

~45P e>2345Y«TG;Y[UG DNA k3oe RNA ¨©?

T DNA xn3eTUW>23?Lj[TvD>F!x¡¢v

DNA º»>¦§JKLM}

?t½uDEFTaq DNA HIJKLMz Tth;eRNA x[TGRNA ;nEFVGpY¼½cÜ

DNA HIJKLMx 20 hi

RNA¾r(AU)10ÀÝÞ89;nT67 (RNA)x|4v (-Y¨©_K]\L;vD

DNA(AT)n Y

3 .)xkl?PeTUvvFGC>

[TG;xewT[62]Uyet ?[·FÛFÜ-e> >}Ç9¬F

ÆBCDSnSUVÇF DNA |4?0

RNA Y$Õ%&;vDF¦§JKLMº»?E
TG;xúuUGDNA xew

nFRNA  DNA á±xÄewDSnSUVG

DNA >FDNA HIJKeµ¶>FRNA  DNA YÛFÜ-eewT¦

LM?EW 20000 hiDNA ¤;

ewTG;túuURNA 45P§JKLM?ü¨vF

RNA  DNA ¤PnYv¾- 4 .ÀUB?FDNA H

?½SD>F- 2 .evm?opeTU

IJKLM?.úõúuDST

vxuDFhi}Ç

RNA _L²?ÁÂI \Lx3ovDSC£F¦§JKLMDNA Y 20000

DNA ?ewTº»?x¨

vF- 4 .evU! ?C£Fz DNA HIJKLMº»Y¼½cÜÝÞn=?>KÜ^

EtpYZ[T67 Y4

E DNA YewTop»>Õ¹fCTevz[SUvxuDF

mU

euop»>Õ¹fCTUGC¥x>? DNAµ¶>FRNA ;cÜÝÞnTÖ×(RNAacÜ
5.  DNA ? TkÝÞûL)?SDF- 2 .~45P
 ?E45P?BC

GGyeF(1)~45P ¹1F(2)?T67 |4 ¹1F(3)DNA HIJKLM?T¸_y>I¿]¾

RNAÀ?EFDNA x

RNA xF!º»Yt½

DNA ?PBCFGCDNA ?nue>nS;f

DNA ¤ÛFÜ-¹1F(4)º»Y(Fig. 2)UB?FGZ[TcÜÝÞ?T

y>I¿]:º»?EF2 ghi}

RNA DNA 

DNA xF ¸_¹1YGnuUVGe..e>F(1)

Ç(4)?E;w$BC¥YUSF DNA 

nue>nS;f(Fig. 2)Uµ¶x¡@[T

? TG ?SDFqàFDNA zV¦$eT

k?LvD[TU45PFF

DNA ?vF DNA ?

DNA Et±v

ÁÂIx=m?vD45P

RNA x~45P?3ovop»>nE~?BC;SmxrTU2345²enuDST¾- 2 .ÀUWülmYUvnSÁÂI>I"Èë ¸_45PFF~45P?

ìK¢ eI 2'-OH Y 2'-H¸_t3ovDSop»xnE?nu?"È[TG;?E4BCT[65]UVGeF

DwDST[63,64]UvvF2345²eWX

ÁÂI~45Pt
55

Viva Origino 31 (2003) 46- 61

amino acids

deoxyribonucleotides

synthesis
oligopetides

ribonuicleotides
synthesis

templatereverse transcriptase
activity

reversetranscriptation

oligoribonucleotides

oligodeoxyribonucleotides
DNA polymerase
activityelongation

repetitive DNA

RNAmutation
proteingenomic DNA

mRNA, tRNA, rRNA

LIFE
Figure 2. A model for the origin and evolution of genomic DNA
Oligoribonucleotides was synthesized from monoribonucleotides in the presence or absence of catalytic molecules such as a montmorillonite
clay under the prebiotic conditions. Some molecules of the oligoribonucleotides synthesized became to the templates of primordial telomeraselike oligopeptides and the catalysts for the synthesis of oligodeoxyribonucreotides (Right). On the other hand, the oligopeptides was synthesizedfrom amino acids under the prebiotic conditions. Some molecules of the oligopeptides synthesized became to the primordial telomerase-likeoligopeptides and DNA polymerase-like ones (Left). The catalytic oligoribonucleotides and/or oligopeptides synthesized short repetitive
oligodeoxyribonucreotides on the oligoribonucleotide templates by the reverse transcriptional activity. The short repetitive
oligodeoxyribonucreotides was elongated to long repetitive DNAs by primordial oligopeptides which have the DNA polymerase-like activity.
The long repetitive DNA was evolved to genomic DNA through nucleotide substitution, deletion, and insertion (Center).

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