Theoretical analysis indicates Genome is not a blueprint and oocytes have the

Koichi Itoh (1)

1: The Institute for Theoretical Molecular Biology
21-13, Rokurokuso-cho, Ashiya, Hyogo, JAPAN, 659-0016
TEL: +81-797-35-6368
FAX: +81-797-35-6368

Corresponding author: Koichi Itoh
1: The Institute for Theoretical Molecular Biology
Room204, 2-9 Shinnouzuka-cho, Ashiya, Hyogo, JAPAN, 659-0016
TEL: +81-797-35-6368
FAX: +81-797-35-6368


Genome has been thought to be a blueprint, but what type of the blueprint has been a
mystery. We have been thought that Genome is not a blueprint. Genome is storage of genes.
An assembly instruction exists in oocytes. After fertilization, zygotes express genes
according to the instruction. We get this result from the survey of Databases. Oocytes
express several types of genes for blastula development and tissue differentiation such as
Zinc finger proteins, Homeobox proteins, Pou homeobox proteins, Forkhead box proteins,
High-mobility group proteins, Sex determination proteins, WNT and PAX. This result
indicates that oocytes have the instruction. Finally, we foresee that once organogenesis
begins tissue differentiation proceeds autonomously and human bodies are built.


 After Human Genome Project was over and human genome sequence was determined,
we expected that a blueprint existed in the genome. However we could not find any traces
of the blueprint. 1) If Genome is a blueprint, it must have the regularity in the sequence.
But there is no regularity. For example, within Genome, there are a lot of psudogenes. 2) In
glycolysis pathway enzymes, hexokinase1 is located in 10q22, glucose-6-phospate
isomerase is located in 19q13.1, phosphofructokinase, liver type is located in 21q22.3,
phosphofructokinase, muscle type is located in 12q13.3, phosphofructokinase, platelet type
is located in 10p15.3-p15.2, aldolase is located in 16p11.2, triosephosphate isomerase is
located in 12p13, glyceraldehydes-3-phosphate dehydorogenase is located in
12p13.31-p13.1, phosphoglycerate kinase is located in 6p21.1-p12, phosphoglycerate
mutase is located in 10q25.3, enolase 1 is located in 1pter-p36.13, enolase 2 is located in
12p13, enolase 3 is located in 17pter-p12, pyruvate kinase , liver and red blood cell type
is located in 1q21 and pyruvate kinase muscle type is located in 15q22. You can find easily
a lot of examples like this in other pathways. In glycolysis, important genes for enzymes
are not located in the near portion on Genome. These 2 examples are enough for show you
that Genome is not a blueprint. We have been thinking that the instruction exists in oocytes.
Unfortunately, at that time, methods for massive gene expression profiling and Databases
were premature and we could not get enough data to answer the question. But now owing
to the spread of microarray analysis and large scale expression profilings, we can easily get
the data we want and Databases pile up enormous data.

Database survey
 In 2006, Kocabas et al. reported the gene expression profile of human oocytes(1). In that
profile, we paid attention for genes for transcription. We thought that among those genes,
genes for instruction existed. We surveyed those genes in NCBI (National Center for
Biotechnology) Databases. We found genes for1)Zinc finger proteins are large and diverse
group of proteins in which the DNA-binding region contains projections ("fingers") with
Cys and/or His residues folding around zinc atom. Some examples are GATA factors
important in the development of the blood and the gut, Kruppel in the early Drosophila
embryo, Krrox20 in the rhombomeres of the hindbrain. 2) Pou homeobox proteins are
related to pituitary development and neural fate. 3) Homeobox proteins have a special role
in the control of anteroposterior pattern in animals. 4) High-mobility group and Sex
determination are related sex determination. 5) Forkhead box are related to head
development and liver formation. 6) PAX proteins are related neural specification and eye
development(2-7). LHX5 is related to control of differentiation and development of the
forebrain. TBX3 plays a role in the anterior/posterior axis. TBX5 plays a role for heart
development and specification of limb identity. TCF15 plays a role for transcriptional
regulation of patterning of the mesoderm (Table1). These genes are essential for blastula
development and tissue differentiation. And genes for DNA maintenance and remodeling,
cell cycle, transcription factors or transcription factor subunits are also essential for the
expression of genes for metabolism, cell growth, and cytoskeleton. You can find genes for
Oct3/4,   Sox2,   Klf4   and   c-Myc  in
htm. These four are essential for the generation of iPS cells(8). We can indicate that the

number of genes related in development is very large.
Here we indicate that after fertilization, oocytes express genes for blastula development
and tissue differentiation. We show the evidence that Genome is not the blueprint and
oocytes have the instruction from the theoretical point of view. Kocabas reported only
up-regulated genes, that is why all essential genes for blastula development and tissue
differentiation were not included in their lists. However, in the near future, experimental
biologists will find all essential genes for blastula development and tissue differentiation.
We surveyed Pathways for development in KEGG (Kyoto Encyclopedia of Genes and
Genomes; and Transpath: The Pathway Database;, but we could not find any pathways for development. From now
on, pathways for blastula development and tissue differentiation will be elucidated. Finally,
we foresee that once organogenesis begins tissue differentiation proceeds autonomously
and human bodies are built.


  1. Kocabas, A. M. et al. (2006). The transcriptome of human oocytes. Proc. Natl Acad. Sci.
    USA 103, 14027-14032
  2. Slack, J.M.W. Essential Developmental Biology, second edition, (2006) (Blackwell
  3. Gilbert, S.F. Developmental Biology, eighth edition, (2006) (Sinauer Association Inc.)
  4. Alberts, B. et al. (2008). Molecular Biology of the Cell, Fifth edition (Garland Science)
  5. Schoenwolf, G..C. et al. (2009). Larsen's Human Embryology, Fourth edition,
    (Churchill Livingstone)
  6. Wolpert, L. et al. (2007). Principles of Development, Third edition, (Oxford University
  7. Moody, S.A. (2007) Principles of Developmental Genetics (Academic Press)
  8. Takahashi, K. et al. (2007). Induction of pluripotent stem cells from adult human
    fibroblasts by defined factors. Cell 131, 861-72


Table1. Up-regulated genes in human Oocytes>>

Table1. Significantly expressed genes in human Occyte  
Unigene ID Symbol Gene name Group
Hs.37706 ZCCHC8 Zinc finger, CCHC domain containing 8 Zinc finger
Hs.523710 ZDHHC18 Zinc finger, DHHC-type containing 18
Hs.27239 ZDHHC5 Zinc finger, DHHC-type containing 5
Hs.592065 ZDHHC7 Zinc finger, DHHC-type containing 7
Hs.612084 ZHX1 Zinc fingers and homeoboxes 1
Hs.507355 ZNF10 Zinc finger protein 10
Hs.479874 ZNF136 Zinc finger protein 136
Hs.592591 ZNF148 Zinc finger protein 148
N.D ZNF161 N.D
Hs.155204 ZNF174 Zinc finger protein 174
Hs.172979 ZNF177 Zinc finger protein 177
Hs.112556 ZNF202 Zinc finger protein 202
Hs.530988 ZNF237 zinc finger protein 237 isoform 1
Hs.59757 ZNF281 Zinc finger protein 281
Hs.484324 ZNF354A Zinc finger protein 354A
Hs.659797 ZNF558 Zinc finger protein 558
Hs.655107 ZNF559 Zinc finger protein 559
Hs.13323 ZNF574 Zinc finger protein 574
Hs.709730 ZNF586 Zinc finger protein 586
Hs.388024 ZNF76 Zinc finger protein 76 (expressed in testis)
Hs.38004 ZNF77 Zinc finger protein 77
Hs.37138 ZNF85 Zinc finger protein 85
Hs.388927 YY1 YY1 transcription factor
Hs.518249 ZNF9 CCHC-type zinc finger, nucleic acid binding protein
Hs.201671 SOX13 SRY (sex determining region Y)-box 13 Sex determination
Hs.95582 SOX15 SRY (sex determining region Y)-box 15
Hs.529462 SOX30 SRY (sex determining region Y)-box 30
Hs.657542 SOX5 SRY (sex determining region Y)-box 5
Hs.493649 POU2F1 POU class 2 homeobox 1 Pou homeobox
Hs.182505 POU3F2 POU class 3 homeobox 2
Hs.654522 POU4F1 POU class 4 homeobox 1
Hs.249184 POU5F1 POU class 5 homeobox 1
Hs.67397 HOXA1 Homeobox A1 Homeobox
Hs.592172 HOXA13 Homeobox A13
Hs.660918 HOXA7 Homeobox A7
Hs.83465 HOXD1 Homeobox D1
Hs.152414 HOXD13 Homeobox D13
Hs.714377 HMG20A High-mobility group 20A Hight-mobility group
Hs.406534 HMG20B High-mobility group 20B
Hs.588815 HMG2L1 High-mobility group protein 2-like 1
Hs.518805 HMGA1 High mobility group AT-hook 1
Hs.434953 HMGB2 High-mobility group box 2
Hs.555947 LEF1 Lymphoid enhancer-binding factor 1
Hs.236774 HMGN4 High mobility group nucleosomal binding domain 4
Hs.546573 FOXD3 Forkhead box D3 Forkhead box
Hs.289292 FOXL2 Forkhead box L2
Hs.239 FOXM1 Forkhead box M1
Hs.370666 FOXO1A Forkhead box O1
N.D FOX3A Forkhead box 3A
Hs.29764 WNT6 wingless-type MMTV integration site family, member 6 WNT
Hs.654389 CUTL1 Cut-like homeobox 1 homeodomein family of DNA binding protein
Hs.162032 HBP1 HMG-box transcription factor 1 HMG-box transcription factor 1
Hs.302029 LHX5 LIM homeobox 5 control of differentiation and development of the forebrain
Hs.443881 PAXIP1 PAX interacting protein 1 paired box (PAX) gene
Hs.129895 TBX3 T-box 3 play a role in the anterior/posterior axis
Hs.381715 TBX5 T-box 5 heart development and specification of limb identity.
Hs.437 TCF15 Transcription factor 15 (basic helix-loop-helix) transcriptional regulation of patterning of the mesoderm
Hs.33102 TFAP2B Transcription factor AP-2 beta  developmentally regulated activator
Hs.696032 PPARD Peroxisome proliferator-activated receptor delta nuclear hormone receptor
Hs.655020 MXD4 MAX dimerization protein 4 regulation of cell growth in differentiating tissues
Hs.517948 DHX30 DEAH (Asp-Glu-Ala-His) box polypeptide 30 putative RNA helicases
Hs.191518 DHX9 DEAH (Asp-Glu-Ala-His) box polypeptide 9
Hs.397465 HIPK2 homeodomain interacting protein kinase 2 serine/threonine nuclear kinase
Hs.471991 MTF1 Metal-regulatory transcription factor 1 Metal-regulatory transcription factor
Hs.483616 RNF14 Ring finger protein 14 ubiquitination
Hs.561815 STAU2 Staufen, RNA binding protein, homolog 2 RNA binding protein
Hs.285354 MAX MYC associated factor X cell proliferation, differentiation and apoptosis
Hs.638121 CRK V-crk sarcoma virus CT10 oncogene homolog (avian) signal transduction
Hs.437075 CREB5 CAMP responsive element binding protein 5 CRE (cAMP response element)-binding protein
Hs.654952 POLR2J Polymerase (RNA) II (DNA directed) polypeptide J, 13.3kDa RNA polymerase II subunit
Hs.567494 YBX2 Y box binding protein 2 Y box family of nucleic acid-binding proteins
Hs.385998 WDHD1 WD repeat and HMG-box DNA binding protein 1 signal transduction/DNA maintenance and remodeling
Hs.26516 ASF1B ASF1 anti-silencing function 1 homolog B (S. cerevisiae) DNA maintenance and remodeling
Hs.162233 CHD4 Chromodomain helicase DNA binding protein 4
Hs.202672 DNMT1 DNA (cytosine-5-)-methyltransferase 1
Hs.713611 DNMT3B DNA (cytosine-5-)-methyltransferase 3 beta
Hs.368322 CDH8 chromodomain helicase DNA binding protein 8
Hs.144287 HEY2 hairy/enhancer-of-split related with YRPW motif 2
Hs.368971 NCOA6 Nuclear receptor coactivator 6
Hs.589489 SMARCA5 SWI/SNF related, matrix associated, member 5
Hs.558463 MSX2 Spen homolog, transcriptional regulator (Drosophila)
Hs.184298 CDK7 Cyclin-dependent kinase 7 Cell cycle
Hs.436975 CLOCK circadian locomoter output cycles kaput protein
Hs.79353 TFDP1 Transcription factor Dp-1
Hs.348418 DR1 down-regulator of transcription 1 transcription factor OR transcription factor subunit
Hs.654393 E2F1 E2F transcription factor 1
Hs.591015 ELK3 ELK3, ETS-domain protein (SRF accessory protein 2)
Hs.25647 FOS V-fos FBJ murine osteosarcoma viral oncogene homolog
Hs.654350 GABPB2 GA binding protein transcription factor, beta subunit 2
Hs.406157 HSF2BP heat shock transcription factor 2 binding protein
Hs.534074 NFATC1 Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Hs.632209 NFATC3 Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3
Hs.631886 REL V-rel reticuloendotheliosis viral oncogene homolog (avian)
Hs.514276 SP2 Sp2 transcription factor
Hs.443258 SREBF2 Sterol regulatory element binding transcription factor 2
Hs.153088 TAF1A TATA box binding protein (TBP)-associated factor, RNA polymerase I, A, 48kDa
Hs.122752 TAF2 TAF2 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 150kDa
Hs.18857 TAF4 TAF4 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 135kDa
Hs.590872 TBP TATA box binding protein
Hs.486507 TBPL1 TBP-like 1
Hs.26837 TRIM33 Tripartite motif-containing 33
Hs.460988 CBFB Core-binding factor, beta subunit
Hs.555985 NARG1 NMDA receptor regulated 1 unknown
Hs.440219 UBN1 Ubinuclein 1
Hs.573153 TCF7 Transcription factor 7 (T-cell specific, HMG-box)
Hs.12229 KLF11 Kruppel-like factor 11
Hs.428027 PBX3 Pre B-cell leukemia homeobox 3
Hs.92236 MLL4 Myeloid/lymphoid or mixed-lineage leukemia 4
Hs.90753 HTATIP2 HIV-1 Tat interactive protein 2, 30kDa
Hs.528641 SIRT7 Sirtuin (silent mating type information regulation 2 homolog) 7 (S. cerevisiae)
Hs.271940 ELF4 E74-like factor 4 (ets domain transcription factor)
Hs.463045 GCN5L2 GCN5 general control of amino-acid synthesis 5-like 2 (yeast)
Hs.530539 NFRKB Nuclear factor related to kappaB binding protein
Hs.127950 BRD1 Bromodomain containing 1
Hs.286145 MED21 mediator complex subunit 21
N.D. not detected in NCBI Database
Supplementary Data 1 - HO 5331

Supplementary Data 2- HO 7074

Supplementary Data 3- HO 7560