Theoretical analysis indicates human genome is not a blueprint but a storage of genes, and human oocytes have an instruction.

Koichi Itoh
The Institute for Theoretical Molecular Biology
21-13, Rokurokuso-cho, Ashiya, Hyogo, JAPAN 659-0011
TEL: +81-797-35-6368 FAX: +81-797-35-6368
http://www.i-tmb.com/
E-mail: koichiitoh@yahoo.co.jp
Corresponding author: Koichi Itoh
The Institute for Theoretical Molecular Biology
21-13, Rokurokuso-cho, Ashiya, Hyogo, JAPAN 659-0011
TEL: +81-797-35-6368 FAX: +81-797-35-6368
E-mail: koichiitoh@yahoo.co.jp
http://www.i-tmb.com/

Abstract
Is Human Genome really a blueprint? If it is not a blueprint, how are human bodies constructed? Firstly, this paper solves this proposition. I indicate 9 examples of important biological pathways and factors among house-keeping gene products and proved that human genome is not a blueprint. Loci of genes in biological pathways of 9 examples are scattered at random in Human Genome in one-dimension. If the Human Genome is the blueprint, 9 important exceptions are not acceptable. That is why Human Genome is not a blueprint but a storage of genes. Secondly, I proved that human oocytes have an instruction for development and differentiation. In this case, I used opened public database for expression profiles of human oocytes. I discovered a number of genes expressed in human oocytes which is more than 20,000 genes. That indicates human oocytes have the instruction for human body planning. Here I show that human genome is not a blueprint but a storage of genes, and human oocytes have the instructions.

1. Introduction
Human Genome has been thought to be a blueprint, but what type of the blueprint has been a mystery. Human Genome project was over in 2003, and 15 years has already passed, but even the number of human genes still unknown. Analysis of human genomes has been continuously done, but the discussion which Human Genome is a blueprint has not been done. Far from that, any traces of a blueprint are not found in Human Genome. This must be one of evidence that Human Genome is not a blueprint. The Watson-Click’s DNA double helix is very beautiful. Hence, we life-scientists might have been imprinted that Human Genome is a blueprint. If we hypothesize that Human Genome is a blueprint, what types of absurdity do emerge? And if Human Genome is not a blueprint, what must be needed to construct human bodies? To solve these propositions are the aim of this document1, 2

2. Materials and Methods
Table I was made from NCBI database OMIM (https://www.ncbi.nlm.nih.gov/omim/) and a Biochemistry Text book3. Supplemental Table I was made from NCBI gene expression data of genes expressed in human oocytes. (https://www.ncbi.nlm.nih.gov/).

3. Results and Discussion
Proposition 1. Human genome is not a blueprint but a storage of genes. I scrutinized loci of genes for 9 important biological pathways and factors, and those loci are scattered all over Human Genome at random (Table I). I think that a blueprint must have the rule such as regularity, periodism, harmony, some types of patterns, or beauty which a blueprint itself has. But there do not exist such things. The loci of genes for 9 pathways and factors are scattered all over Human Genome at random in one-dimension. There are no reports that scattered genes in one-dimensional construct clusters in three-dimensional. Is it necessary that Human Genome make clusters in three dimensional in nuclei? Proteins make complexes and work in cytoplasm or are secreted from cells. Human Genome do not need to make clusters in three- dimensional in nuclei. It is enough to be a storage of genes in one-dimension. If genes make clusters in three dimensional, there must exist thousands or more clusters in a nucleus. For example, several enzymes work in deferent biological pathways. It is not logical because Human Genome must easily tangle. In mathematics, sometimes one opposite example is enough for proof. But biology has many exceptions. However, genes in Table I are biologically important genes, and if a human genome is a blueprint, 9
exceptions must not be acceptable. I think that 9 exceptions are enough evidence. I already surveyed more than 20 pathways and I had the same results. Even if I survey more than 100 biological pathways, the result must be the same.Therefore, I logically prove that a human genome is not a blueprint. Human Genome is just a storage of genes.
Proposition 2. Human oocytes have the instructions. Before fertilization, human oocytes express genes. If a Human Genome is storage of genes, mRNAs which are important for development and differentiation must be expressed in human oocytes and translated into proteins before fertilization begins. Therefore, I surveyed the database and I find more than 20,000 genes are expressed in human oocytes. In general, many sample data must be necessary for comparison of gene expression levels for statistical analysis. But in this case, I do not need to compare gene expression levels. Because the importance is what types of genes are expressed in human oocytes. As a result, almost all genes are expressed in human oocytes. That indicates human oocytes have the instruction to build human bodies if human oocytes do not have the simple instruction, BY the way, where is the instruction? I already indicate that a human genome is not a blueprint. Hence, it is logical that human oocytes have the simple instruction because a human body begins to be built from only one cell, a fertilized egg. In case of In Vitro Fertilization (IVF),
fertilized eggs develop and differentiate from only one cell. Therefore, I logically proved that human oocytes have the simple instruction. Hence, I think that Human Genome begins to exist as just a storage of genes. And human oocytes express essential genes for development and differentiation as the simple instruction. After fertilization, a fertilized egg differentiates according to micro-environment surround the fertilized egg. From now on, a lot of evidence will be piled up to support my hypothesis. Finally, I foresee that once organogenesis begins, tissue differentiation proceeds autonomously and human bodies are built. Here I show that Human Genome is not a blueprint but a storage of genes, and Human oocytes have the instruction.

Reference

1. K Itoh, Theoretical analysis indicating that human genome is not a blueprint and that human oocytes have the instructions, J. Compute. Biol. Bio inform. Res, 3 (2011) 1-7. 2011.

2. K Itoh, Theoretical Molecular Biology, LAP LAMBERT Academic Publishing (2011).

3. Harper’s Illustrated Biochemistry 30th Ed. (2015).
Table I. Loci of genes for major biological pathway.

1.Glycolysis

Gene Name Locus
Glucokinase (Hexokinase 4) 7p13
Glucose 6-phosphatase 17q21.31
Hexokinase 1 10q22.1
Hexokinase 2 2p12
Hexokinase 3 5q35.2
Phosphoglucose isomerase 19q13.11
Phosphofructokinase, Liver Type 21q22.3
Fuctose-1,6-bisphosphatase 9q22.32
Aldolase A 16p11.2
Aldolase B 9q31.1
Aldolase C 17q11.2
Triose phosphate isomerase 12p13.31
Glyceraldehyde 3-phosphate dehydrogenase 12p13.31
Phosphoglycerate kinase 1 Xq21.1
Phosphoglycerate mutase 10q24.1
Enolase 1 1p36.23
Enolase 2 12p13.31
Enolase 3 17p13.2
Pyruvate kinase, liver and RBC 1q22

2.TCA cycle

Gene Name Locus
Aconitase 22q13.2
Isocitrate dehydrogenase 15q26.1
alpha-ketoglutarate dehydrogenase 7p13
dihydrolipoyl dehydrogenase 7q31.1
dihydrolipoyl succinyltransferase 14q24.3
succinate-CoA Ligase, alpha subunit 2p11.2
Succinate-CoA Ligase, ADP-Forming, beta subunit 13q14.2
Succinate dehydrogenase 5p15.33
Fumarase 1q43
Malate dehydrogenase 7q11.23
Citrate synthase 12q13.3

3.Pentose phosphate pathway

Gene Name Locus
Glucose-6-phosphate dehydrogenase Xq28
6-phosphogluconolactonase 19p13.11
3-epimerase 2q34
ribose-5-phosphate isomerase 2p11.2
transketolase 3p21.1
transaldolase 11p15.5
Phosphohexose isomerase 19q13.11
aldolase A 16p11.2
aldolase B 9q31.1
aldolase C 17q11.2
triose-phosphate isomerase 12p13.31
fructose 1,6-bisphosphatase 9q22.32
phosphohexose isomerase 19q13.11

4.Urea cycle

Gene Name Locus
Carbamoyl phoshpate synthase I 2q34
Ornithine transcarbamylase Xp11.4
Argininosuccinate synthase 9q34.11
Argininosuccinate lyase 7q11.21
Arginase 6q23.2

5.Fatty acid metabolism

Gene Name Locus
long-chain acyl-CoA synthetase 4q35.1
acyl-CoA dehydrogenase 1p31.1
acyl-CoA oxidase 17q25.1
enoyl-CoA hydratase 10q26.3
3-hydroxyacyl-CoA dehydrogenase 4q25
long-chain 3-hydroxyacyl-CoA dehydrogenase 2p23.3
acetyl-CoA acyltransferase 18q21.1

6.Purine biosynthesis

Gene Name Locus
phosphoribosyl pyrophosphate synthetase Xq22.3
phosphoribosy lpyrophosphate glutamyl  amidotransferase 4q12
phosphoribosylglycinamide formyltransferase 21q22.1
phosphoribosylformylglycinamidine synthetase 17p13.1
phosphoribosylaminoimidazole carboxylase 4q12
phosphoribosylaminoimidazole synthase 21q22.11
adenylosuccinate lyase 22q13.1
5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase 2q35
IMP cyclohydrolase 2q35
adenylosuccinate synthetase 1q44
IMP dehydrogenase 7q32.1
GMP synthetase 3q25.31

7.Pyrimidine biosynthesis

Gene Name Locus
carbamoyl-phosphate synthase 2p23.3
aspartate transcarbamoylase 2p23.3
dihydroorotase 2p23.3
dihydroorotate dehydrogenase 16q22.2
orotate phosphoribosyltransferase 3q21.2
orotidylic decarboxylase 3q21.1
CTP synthase 1p34.2
ribonucletotide reductase, M1 subunit 11p15.4
ribonucletotide reductase, M2 subunit 2p25.1
thymidylate synthetase 18p11.32

8.beta-oxdation of fatty acids

Gene Name Locus
Acyl-CoA synthetase 4q35.1
Acyl-CoA dehydrogenase 1p31.1
delta2-enonl-CoA hydratase 19q13.2
L(+)-3-hydroxyacyl-CoA dehydrogenase 4q25
thiolase 2p23.3

9.Biosynthethis of long chain fatty acids

Gene Name Locus
Malonyl-CoA Decarboxylase 16q23.3
Acetyl CoA carboxylase 17q12
3 ketoacyl synthase 3p24.2
3 ketoacyl reductase Xp11.22
Hydratase 10q26.3
Enoyl reductase 19p13.12
Thioesterase 1p36.31
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