Theoretical analysis indicates Genome is not a blueprint and oocytes have the
instruction.
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
e-mail: itoh@i-tmb.com
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
e-mail: itoh@i-tmb.com
Summary
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
http://www.crl.msu.edu/Supp%20WEB/Kocabas%20et%20al%20Supp.%20Web%20Index.
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.
Discussion
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 et.al 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; http://www.genome.ad.jp/kegg/) and Transpath: The Pathway Database;
http://www.transpath.de/), 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.
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