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 |

