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HEREDITICS (A COMPLETE STUDY OF HEREDITY) AND
ORIGIN OF LIFE

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Ke-Hui Cui M.D., Ph.D.

Savannah, Georgia, 31405, U.S.A.

September 25, 2020

Email: khcui72@hereditics.net

Edited by Dr. YongYan Cui

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Abstract

Human beings have evolved over 5 million years and maintained an intact heredity of both the genome and cytoplasm. The origin of heredity has been traced to the origin of life - a combination of RNA and cell membrane. The origin of life suggests that the cytoplasm acquired hereditary functions with RNA long before DNA existed on earth. Four components of human heredity are: hereditary messages (DNA and genes), hereditary structure (cell), hereditary action (cell division), and hereditary expression (differentiation). The study of heredity (Hereditics) should include both Genetics and Cytohetics (study of the heredity of cytoplasm). Cytohetics shows that hereditary diseases are not only due to defects of DNA, but also due to concurrent defects in the heredity control system (checkpoint and licensing system). Cytohetics and Epicytohetics (the study of expression of cytoplasm) may be very helpful to research of cell differentiation, cancer, neuropathic diseases, immune diseases, and other system and organ diseases. Hereditics will expand new concepts in physiology, cellular biology, and many fields of life science, including pharmacology and stem cell research for non-germline therapy. For example, in the reproductive field, Hereditics can elucidate how mitochondrial replacement therapy (MRT) disturbs hereditary materials (i.e. cytoskeletons and the heredity control system) and how it affects differentiation and produces subhuman beings with inferior species quality (MRT syndrome). Hereditics also demonstrates that both cloning in human reproduction and preimplantation genetic screening are neither scientific nor safe.

 

Key words: heredity; genetic; mitochondria; microtubule; cell; preimplantation genetic testing for aneuploidy

 

 

What is a complete hereditary material?(in lay language)

When an egg is opened, the yolk and egg white are present. Which contains the hereditary material? Some people may say: “The yolk”. The simple reason is: DNA and genes are mainly in the yolk. Other people may guess: “The whole egg?”

 

The correct answer is "the whole egg". Both egg yolk and egg white are hereditary material, according to recent scientific research results, which will be explained in the following sections. Some new and old concepts related to heredity are:

  1. Hereditics1—the complete study of heredity, i.e. the study of heredity of the whole egg (in lay language), as the whole egg produces offspring. Hereditics includes Genetics and Cytohetics:

  2. Genetics—the study of genes and DNA, i.e. the study of heredity of the egg nucleus (in lay language).

  3. Cytohetics—the study of cytoplasmic heredity, i.e. the study of heredity of the egg cytoplasm (in lay language).

  4. Epigenetics—the study of the expression of genes, i.e. how the egg genome and its genes develop into different organs and tissues.

  5. Epicytohetics—the study of the expression of the cytoplasm, especially in differentiation of the cytoplasm, i.e. how the egg cytoplasm develops into different organs and tissues.

Web drawing - Hereditics 1.png

Two animal models are the examples of the new concepts of Cytohetics and Epicytohetics. They showed results of altered phenotype in the offspring when the sole cytoplasm (or cytoskeletons) was changed. In the first model, freshwater animal Hydra was excised. The axis direction of actin (i.e. the polarity) in the excised pieces determined whether the regenerating offspring would be normal (single body axis) or abnormal (multiple body axes). When the excised polarity was abnormal, about two-thirds of offspring had abnormal body axes or multiple axes. However, when the excised polarity was normal, only about 10% of offspring had abnormal body axes or multiple axes2. This study confirmed that damage of the cytoskeleton (rather than DNA) can produce abnormal expression in the offspring. In the second model, cloning one Polo horse of the same genotype (i.e. the same genome or DNA) produced many different cytotype (or phenotype) in the cloned offspring because they were cloned with different cytoplasm of the recipient oocytes. The different recipient cytoplasm contain different cytoplasmic spatial structures, polarity, and cytoskeleton configuration after their nuclei were removed. This caused many different phenotypes, including varied defects and abilities, to be produced in the cloned Polo horses3. Thus the owner can recognize each of his cloned horses.

 

Facts of both gene and cytoplasm inheritance

Gregor Mendel first reported discrete “units of inheritance” of phenotypic traits based on experiments differentiating characters of pea plants by fertilization4. Models of double-stranded DNA molecules5 strengthened the theory that heredity is related to genes and DNA. Genetics has been defined as the study of genes, genetic variation, and heredity in living organisms6. However, if some define genetics as the unique study of heredity, this would be incorrect6. If genes and DNA were the only materials required for heredity, genome transfer directly into culture media rather than into ooplasm should produce offspring of the said species. Recognition of the hereditary function of the cytoplasm is critical.

 

In the cytoplasm, most organelles are inherited. Mitochondria are essentially maternally inherited7. The dynamics of a living cytoskeleton are also inherited8 by means of self-organization or self-assembly9. The endoplasmic reticulum (ER) spreads throughout the eukaryotic cell and is contiguous with the nuclear envelope, its distribution and dynamics in yeast might be conserved in animal cells10. Centrosome and centriole are also inherited11,12. Thus, the cytoplasm and its organelles are similar to genes and DNA as they are hereditary materials.

 

Different inheritance patterns in genes and in cytoplasm

Cell division (mitosis and meiosis) is a crucial mechanism in heredity and life. If there was no cell division, there would be no cell heredity. If DNA and genes are replicated and the cell is not divided, the DNA and genes cannot be inherited to progeny cell(s).

 

The inheritance of genes and DNA occurs by replication13 and cell division. The inheritance of the cytoplasm and its organelles is different and occurs by duplication and cell division14.

 

In humans, during each somatic cell cycle, the chromosomes, cytoplasm, and centrosomes duplicate in interphase, and all of them split in two during mitosis14.

 

Meiosis differs between human sperm and oocytes. Human sperm have centrioles. A well-defined proximal centriole is present next to the basal plate of the sperm head, while the distal centriole gives rise to the central strand of the sperm tail flagellum15. In contrast, in oocyte meiosis, human meiotic spindles have centrosomes but no centrioles15. Oocyte centriole reduction plays an important role in preventing parthenogenesis and ensuring biparental fertilization16. The maternal γ-tubulin (the component of the reduced oocyte centriole) is often localized at the egg cortex17, ensuring that the sperm centriole will easily bind to this microtubule-nucleating protein.

 

During fertilization, both the sperm and the egg contribute equal haploid genomes14. However, fertilization is an uncommon process of inheritance of cytoplasm, in which oocyte centrioles are first reduced during oogenesis and then combine with the sperm centriole to restore the zygotic centrosome. The egg contributes to the vast majority of zygote’s cytoplasm14. In summary, the zygotic centrosome is the blending of maternal and paternal constituents, with the maternal centrosomal components (including γ-tubulin) attracted to the paternal “seed” – the proximal centriole of the sperm14,15.

 

Cytohetics: Centrosome and heredity control system

The centrosome in cytoplasm was discovered in 187618. The centrosomes are the command centers for cellular control, in both cell division (cytokinesis) and cell-cycle progression19. Recent identification of many kinds of RNA and more than three hundred kinds of proteins in and around centrosomes have highlighted the evolutionary conservation of centrosome functions20,21. The centrosome not only serves as the microtubule organizing center, but also as the actin organizing center, the intermediate filament organizing center, and the Golgi organizing center14,22,23,24. Because centrosomes organize actin, microtubules and orient the spindle, any change in the centrosomes can block or impede cell division25,26.

 

Heredity in most species is very stable. Human beings have a history of about five million years of repetitive cell division, and still have conserved a karyotype of 46 chromosomes and an intact cytoplasm. Aneuploid cells are produced continuously throughout life from our embryonic stage until our death. Yet why are most people not characterized as being aneuploidy or affected by mosaicism? This is because the cytoplasm of eukaryote cells contains several families of protein kinases such as cyclin-dependent kinases (Cdks), polo-like kinases (Plks), Aurora family of kinases27, and many other families of proteins to form a heredity control system. This system includes checkpoint and licensing factors for DNA replication28,29,30, for centrosome duplication20,31,32 and for spindle assembly33,34,35,36. The cycles of centrosome duplication and DNA replication are coordinated, and rely on these proteins in the cytoplasm and centrosome for regulation. For example, one of the centrosomal substrates, cdk2, couples with centriole duplication at the onset of DNA replication, i.e. the G1/S phase transition. The G1/S phase regulating proteins include cyclins D and E, cdk4 and 6, cdk inhibitors p53, ZYG-1, Aurora kinases, etc. They regulate the G1 phase to be finished before progression into the S phase. Otherwise, the cells would arrest in the G1 phase37,38. Additionally, Plks are important mediators for various cell cycle checkpoints that monitor centrosome duplication, DNA replication, segregation of chromosomes, and mitotic exit27. The checkpoint and licensing system is named for its biological function. The checkpoint and licensing system can also be called the heredity control system when considering its heredity function. It prevents aneuploid cells from passing through the mitotic exit20. The mitotic exit functions as a “switch” of heredity in the cytoplasm27. When it is “turned on”, one cell can divide into two cells, and heredity from cell to cell will happen. In animals, cell-to-cell heredity of an embryo will ultimately lead to life-to-life heredity. When the mitotic exit is “turned off” by heredity control system, the aneuploid cell in the late embryonic stage will not divide and will then undergo apoptosis, thus ending the said mosaic phenomena39.

Web drawing - Hereditics 2.png

In human embryos, especially at blastocyst stage, the checkpoint and licensing system is loose to allow more aneuploid cells to develop. These aneuploid cells are very important and positive phenomena of embryonic physiology: for fast inner cell mass differentiation and for fast villi implantation to obtain nutrition1. Most of these aneuploid cells in human embryos do not contain heredity characteristic due to the perfect heredity control system in their cytoplasm to stop mitotic exit. When coordination between the cell cycle and the heredity control system is damaged, pathological aneuploidies or cancer will occur20,40. The heredity control system is very meticulous. Any cell being divided must pass the checkpoint and licensing system many times. In humans, the natural heredity control system allows fewer than 1% of live births to contain genetic abnormalities, with true mosaicism comprising less than 0.3%41. However, in Preimplantation Genetic Screening (PGS) (i.e. preimplantation genetic testing for aneuploidy, PGT-A) that is performed in some IVF clinics, the patient’s history (which is closely related to how perfect the patient’s heredity control system is) is neglected. PGS is applied broadly to all patients since 2015 in U.S., even they do not have a history of hereditary diseases. As a result, PGS has shown a failure in clinical practice. In fact, the theory behind PGS was refuted after transfer of “mosaicism” embryos resulted in 201 live births of babies with normal karyotypes. The zero percent success rate (0/201) of PGS in predicting the babies’ chromosomal abnormalities42,43,44 exists because those parents contained normal heredity control system. This finding confirms that most (>99%) aneuploid cells (i.e. the abnormal DNA) found by PGS do not function as heredity materials in human embryos. In contrast to PGS, when using the patient’s positive hereditary history as a marker of their compromised hereditary control system (such as cystic fibrosis, in which both the heredity control system and cystic fibrosis gene are defect), preimplantation genetic diagnosis (PGD) has been shown to achieve a 99% correct diagnosis rate in 3755 pregnancies in Europe45. Thus, depending on whether the patient’s hereditary history is considered, the results of preimplantation genetic testing (PGT) is significantly different (p<0.0001) in predicting the baby’s heredity of abnormal aneuploid cells. The combination of the failure of PGS and the success of PGD in clinical practice clearly indicate that hereditary diseases are due to the concurrent defects of both DNA and hereditary control system. The failure of PGS confirms that Cytohetics is very successful (rather than Genetics) in explaining: why the aneuploid cells (DNA) found in PGS embryos lack hereditary characteristics1. Comparing Genetics, Hereditics shows its superiority to elucidate why mosaic human embryos produce normal babies. It is inferred by Hereditics, there are two heredity components in Genetics: hereditary message (DNA and genes) and biological trait. When advanced reproductive techniques such as somatic cell nuclear transfer (SCNT) and mitochondrial replacement therapy (MRT) are performed, the cell’s cytoplasm is physically disrupted and the heredity control system in the oocyte is physically torn and destroyed by spindle extraction. Under the principles of Cytohetics, this damage can lead to hereditary problems (such as Cloning Syndrome or MRT Syndrome) in the SCNT and MRT offspring.

PGS-Not Safe 36 Componenets of Genetics 2.png

Core of Epicytohetics: centriole, its differentiation function and the results of its damage

Centrioles are a core part of centrosome duplication31. Aside from its functions in the organizing centre, mitosis, and cell division, centrioles are essential for cell motility and the formation of microtubule-derived structures, including cilia, flagella, and centrosomes46. The formation of cilia and flagella are the first examples of cytoplasmic differentiation of microtubules. The formation of neuron, immune and muscle systems are recent further examples of cytoplasmic differentiation of microtubules. Without differentiation, animal life and animal heredity would not exist. Thus, in animals, heredity is not only passing on by cell division, but also by cell differentiation.

web drawing - Hereditics 5.png

 

Gamma tubulin is basic unit of centrioles and is conserved in all eukaryotes47,48,49. The γ-tubulin nucleates microtubules50. “The terminal differentiation of the oocyte may be the dispersion of γ-tubulin”14, which allows the oocyte to obtain totipotency by temporary loss of centriole and by reprogramming and retaining its initial zero morphogenetic status. As such, centrioles are the units that regulate the processes of irreversible differentiation, determination, and modification of the morphogenetic status51. In fly species (Drosophila), it has been demonstrated that centrioles are not necessary for somatic cell divisions52 and (centriole-negative) mutants develop into almost morphologically normal (without cilia or flagella) adults. However, their larval neuroblasts are abnormal and these flies have a premature death because their neurons lack cilla53, confirming that centrioles are also hereditary materials in fly species. Although DNA and genes are intact, the heredity of the experimental flies stops because differentiation is incomplete. In animals, heredity is closely related to complete differentiation, which not only depends on normal genome but also depends on normal cytoplasm.

 

Centrioles, microtubules, and other cytoskeletal elements in the cytoplasm are not genes or DNA. They are a complex combination of gene products (proteins). However, they influence cell differentiation into tissues and organs, including the shape of growth cones of neurons, length of neurons, brain morphogenesis, and eye evolution48,54,55. MRT and any change in the cytoplasm will produce a change in expression at the tissue and organ level in heredity with abnormal feedback loops9. Thus an intact cytoplasm (“egg white”) is a very important determinant of normal differentiation, and normal organ and tissue function. The above fly example confirmed that a defective cytoplasm (centriole-negative) is related to the defective cytotype and phenotype.

 

Abnormal polarity leads to abnormal differentiation

Normal oocyte polarity is closely related to normal differentiation. Cell polarity begins in the oocyte with cytoskeletons and is reinforced at fertilization. The axes and polarity are maintained through to the blastocyst state and the differentiation of fetal cells and fetal body56. Although the zygote is totipotent, it is often already a highly polarized cell, in which specific cytoplasmic domains are destined to give rise to specific tissues57. The normal oocyte polarity includes asymmetries in duplication of centrioles and formation of centrosomes58,59. Oocyte polarization is coupled to the chromosomal bouquet, or chromosome territories, a conserved polarized nuclear configuration in meiosis. That is, the polarity of the oocytoplasm is coupled to the polarity of the chromosome territories in three-dimensional spatial configuration60. The polar chromosome territories align to build up higher order compartments in specific orientation of replication, and this organizational principle is inherited in human beings61 through cell division62. SCNT and MRT damage the inherited polarity alignment between the cytoplasm and the nucleus, or genome, by extracting one genome and inserting another genome. SCNT and MRT trigger “profound chromatin rearrangements including the dispersion of the donor cell chromocenters components”63.

 

The microtubules and actin filaments that are reconstructed following SCNT and MRT are not the same as our natural, inherited ones that have been passed down over five million years of evolution of human beings. The damage of microtubules, actin, and their polarity by MRT also influences MRT oocytes or zygotes to differentiate into abnormal neurons, muscle cells, and other cells in different tissues and organs as evidenced below. The abnormal differentiation in MRT is not produced by DNA or gene alteration. It cannot be explained by Genetics or Epigenetics. The abnormal differentiation is produced by the alteration of cytoplasm. It can only be explained by Epicytohetics, i.e. the alteration of expression of the heredity of cytoplasm.

 

Epicytohetics I: Cytoskeleton and neuron differentiation

“Recent data have revealed that the microtubule cytoskeleton is a major determinant in the establishment and maintenance of neuronal polarity. Microtubules provide the structural basis for neuronal polarization, because of their intrinsic properties including inherent polarity”64. The differentiation of the nervous system starts with the growth cone of an axon. “Navigation of the growth cone at the tip of the developing axon is crucial for the proper wiring of the nervous system” 65. The growth cone is a fan-shaped structure that has two domains: central domain (microtubule-rich region) and peripheral domain (actin-rich lamellar region)66. The motility of the growth cone (during axon extension, retraction, and turning) is achieved by actin protrusion first, and then facilitated by microtubules67. And “severing in the labile portion of the microtubule affects the capacity of microtubules to assemble labile portions into the peripheral domain of the growth cone” 65, 68. In addition to the growth cone, axon collateral branches are important during neuronal differentiation, as they allow individual neurons to make contact with multiple neurons within a target and with multiple targets67,69. The normal formation of axon collateral branches is reliant on the normal plus or minus direction of the microtubules70.

 

“The microtubules do not reach from the cell body all the way to the axon terminals; each is typically only a few micrometers in length, but large numbers are staggered in an overlapping array.” The longest axon in human body reaches from the base of the spinal cord to the foot and is up to a meter in length70. Due to the specific positional alignment of over millions and millions of correct direction of plus or minus ends of microtubules in natural intact neurons, our bodies are able to sense and react to stimuli precisely without mistakes. Because SCNT and MRT greatly disturb the natural order and plus or minus direction of microtubules, neurons differentiated from these impaired microtubules will exist in the wrong location and wrong direction, and will not function normally. They will function inferiorly or will have complete absence of function. “Within a neuronal cell, microtubules are found to have variable lengths and can be both stable and dynamic (or turnover, i.e. dynamic exchange between microtubule polymers and free tubulin dimers).” “Reduced microtubule stability has been observed in several neurodegenerative diseases”. In reverse, “hyperstable microtubules also lead to neurodegeneration. Therefore, the ratio of stable and dynamic microtubules is likely to be important for neuronal function and perturbation in microtubule dynamics might contribute to disease progression”71. When microtubules are abnormal, the increased number of dynamic microtubules will lead to increased neuronal branching, shortened neutrites, axons that do not connect to postsynaptic cells, and impaired synapse functioning71. Crucial experiments showed imbalance of damages between motor and sensory neuron: Hyperdynamic microtubules impair axonal transport and accelerate motor neuron degeneration, but not in sensory nerves72. This imbalance of damages compromises the coordination and interaction between motor and sensory nerves, which ultimately predisposes to more injuries or accidents. It has been reported that six of thirteen children born after ooplasmic transplantation73 had a history of injuries or accidents74. The report confirms that the injected ooplasm (containing donor microtubules, actin, and other cellular organelles) disturbed the cytoskeleton of recipient oocytes. These abnormal microtubules could not return to their normal length, numbers, or spatial positions in the recipient oocytes, and such abnormalities were inherited to the differentiated cells. Due to Epicytohetics, they produced abnormal neuron function75, one of the symptoms of MRT syndrome. In addition to high injury and accident rates, many other different neuropathic problems were reported in the 13 children74. The mean GPA of donor’s DNA positive children was also lower than the mean GPA of donor’s DNA negative children.

 

Epicytohetics II: Cytoskeleton and immune system differentiation

Normal cytoskeletons of germline cells are not only important for normal differentiation of the nervous system, but also important for differentiation of other systems. In the immune system, “many cells require rapid cytoskeletal rearrangements for their normal functioning during interphase as well. For example, the neutrophil, a type of white blood cell, chases and engulfs bacterial and fungal cells … by extending a protrusive structure filled with newly polymerized actin filaments. When the elusive bacterial prey moves in a different direction, the neutrophil is poised to reorganize its polarized protrusive structures within seconds”70. Normal functioning of macrophages and lymphocytes (cytotoxic cells or natural killer cells) also depend on the intact cytoskeletal structures70. “Cytotoxic T lymphocytes (CTLs) are highly effective serial killers capable of destroying virally infected and cancerous targets by polarized release from secretory lysosomes … focusing microtubule-directed release at this point”76. “An increasing number of studies have revealed associations between pre- and perinatal immune activation and the development of schizophrenia and autism … neuroimmune crosstalk has a considerably large impact on brain development during early ontogenesis. … The results propose the relevance of altered synaptic vesicle recycling, cytoskeletal structure and signal transduction”77. To put it simply, altered cytoskeletal structure will influence normal development of both neural and immune systems simultaneously. Research has already shown that cytoskeletal defects are closely related to immunodeficiency diseases78 and that the pathogenesis of asthma may be related to the ratio and dysfunction of natural killer T cells79. This point is further supported by children born after ooplasmic transplantation73: Seven out of 13 children suffered from allergies and more had other immune problems74. According to Epicytohetics, immune problems are another consequence of MRT syndrome that cannot be diagnosed by any DNA or genetic tests due to the presence of normal DNA and genes.

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Epicytohetics III: Cytoskeleton and muscle differentiation

In muscles, cytoskeleton actin filaments slide past myosin filaments toward the middle of the muscle unit sarcomere to produce muscle contraction80. “The heart is the most heavily worked muscle in the body, contracting about 3 billion times during the course of a human lifetime. Heart cells express several specific isoforms of cardiac muscle myosin and actin. Even subtle changes in these cardiac-specific contractile proteins – changes that would not cause any noticeable consequences in other tissues – can cause serious heart disease …Familial hypertrophic cardiomyopathy is a common cause of sudden death … another type of heart condition, called dilated cardiomyopathy, which can also result in early heart failure”70. Thus disturbance of cytoskeleton by SCNT and MRT will likely produce severe muscle and heart problems, which will lead to a high stillbirth rate81,82. Stillbirth and other muscle problems may be another consequence of MRT syndrome according to Epicytohetics.

 

The Degree of Side Effects on Heredity (DOSEH) refers to the incidence of a specific heredity side effect after exposure to different types of cytoplasmic damage. They are summarized as:    

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In ovarian hyperstimulation, near none or none of cytoplasmic damage can lead to cancer  (DOSEH ≤ 0.01%).  

In intracytoplasmic sperm injection (ICSI), very mild cytoplasmic damage can lead to sex chromosomal abnormalities (DOSEH = 1%).

In PGT-a, mild cytoplasmic damage from repeated temperature change, embryo biopsy and laser radiation can lead to Embryo Biopsy Syndrome with adverse effects on mental development (DOSEH ≈ 20%).

In oocytoplasmic transfer, medium cytoplasmic damage can lead to MRT Syndrome, presenting as physical accidents or other neuropathic and immune problems (DOSEH ≈ 50%).

In spindle transfer and PNT, heavy cytoplasmic damage can lead to severe effects of MRT Syndrome including embryo growth arrest, stillbirth, early death and infertility, etc. (DOSEH > 50%).

In SCNT, very heavy cytoplasmic damage can lead to SCNT Syndrome, presenting as extremely low birth rate or babies with many health problems (DOSEH > 50-90%).

Very very heavy cytoplasmic damage in centrosome or centrioles will lead to heredity cessation, i.e. death (DOSEH = 100%).

 

Micromanipulation techniques that cause more harm to the cytoplasm and heredity control system will result in higher DOSEH and poorer outcomes in offspring. However, even with cytoplasmic damage by the above micromanipulation techniques, Genetic testing results will all (but ICSI) falsely appear normal in offspring.  As such, Hereditics is more advanced than Genetics in evaluating which different reproductive techniques are safer.

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In brief, cells are the basic unit of the organ systems in the human body. The physical chaos within cellular organelles produced by SCNT and MRT will produce inferior cellular structures, and inferior differentiation of all kinds of cells. These inferior cells produce inferior organs and systems, ultimately producing inferior and subhuman babies rather than normal human babies83,84. These subhuman babies contain normal DNA and genes, i.e. they are normal in Genetics. However, they are abnormal in cytoplasm and differentiation, abnormal in Cytohetics and Epicytohetics.

PGS-Not Safe 34 Componenet of Hereditics.png

Hereditics of eukaryotes

While prokaryotes have short lifespans with cell-to-cell generations known as “cell generation”, the lifespan of most eukaryotes is much longer and can be classified as both “cell generation” (in simple cells) and “life generation” (in animals). The eukaryote gave rise to multicellular form of life with differentiation to multiple tissues and organs. Compared to prokaryotes with smaller genomes, eukaryotes (which are about 2 billion years old) contain larger genomes85. It has been found that eukaryotic genomes resulted from a fusion of two diverse prokaryotic genomes86 and/or from viral invasion87. Eukaryote animal rotifers have received multiple genes from bacteria, fungi, and plants87. The ancestor of the nucleus of the eukaryotes was a complex DNA virus resulting from phagocytosis and other membrane fusion processes. Eukaryotes derived several features from their viral ancestor including mRNA capping, linear chromosomes, and separation of transcription from translation88. It has been suggested that the first eukaryotic cell was derived from the combination of three components: nucleus (from a viral ancestor), cytoplasm (from an archaeal ancestor), and mitochondria (from bacterial ancestor)85,89. Thus, in the evolution of eukaryote, the hereditary materials of eukaryotes involved not only DNA, but also cytoplasm.

 

Centrioles (especially γ-tubulin) evolved early in the history of all major eukaryotes belonging to the domain Eukarya48. Centrosomes serve as the microtubule organizing center of dividing cells90, they evolved much later than centrioles and were restricted to animals and some fungi48,91,92.

 

Hereditics of larger species and sexual reproduction

In most animals, the four key factors in the heredity security system for maintenance of sexual reproduction are centrosomes, recombination at meiosis, diploid cells and the presence of an immune system93,94. The evolution of sex was favored to allow faster adaptation to new environments95. The main function of sex is the preservation of DNA and consequently a higher quality of offspring. Recombination at meiosis evolved, perhaps, as a repair mechanism of DNA strand damages. Meiosis acts also as creator of variation in haploid stages, in which natural selection can efficiently purge most deleterious mutations. Thus, sexual reproduction is favorable for populations when deleterious mutations become more dominant or beneficial mutations become more recessive in genes. A prolonged diploid phase buffers the effects of deleterious recessive alleles as well as epigenetic defects and is thus optimal for prolonged growth periods94,96,97. The evolution of the centrosome in sexual reproduction, which contains the heredity control system (checkpoint and licensing factors), ensures the inheritance of a correct copy of the genome by each daughter cell. All these factors secure heredity quality, making sex more advantageous in the evolution of larger species93.

Web drawing - Hereditics 3_edited.jpg

Hereditics of the last universal common ancestor and RNA world

Eukarya, Archaea, and Bacteria are the three domains of all life forms on earth. The identity of their Last Universal Common Ancestor (LUCA) lived about 3.5 billion years ago87. LUCA started with very simple cellular entities that had inaccurate information processing systems with high mutation rates and lateral gene transfer levels. As increasingly complex and precise biological structures and processes evolved, both the mutation rate and the scope and level of lateral gene transfer dropped. And LUCA became a diverse community of cells that functioned as a biological unit. Its molecular sequences emerged from RNA98. LUCA is also known as the Last Universal Cellular Ancestor or rudimentary cell with a cell membrane, cytoskeleton, respiratory capacity, and most metabolic pathways, but without full genetic information in early LUCA period87,99,100.

 

Both DNA and RNA evolved earlier than LUCA101. There are strong reasons to conclude that simpler RNA evolved earlier than relatively complex, stable, and larger DNA and proteins. This earlier era is referred to as the “RNA world”102,103 as RNA contained multiple autonomous functions acting as both genomic carrier and a polymerase before the evolution of DNA and proteins102,104. LUCA had an RNA genome at the beginning and was called RNA cells105. It has been revealed that the RNAs had a fundamental impact in shaping the genome, heterochromatin formation, and gene creation. About half of our DNA is comprised of repetitive sequences expanded mostly through RNA-mediated processes106, which confirms that some of the DNA sequences were transcribed “in reverse” from RNA87. Over 1,000 genes found in the late LUCA period107 showed the transition from RNA to DNA genomes (“DNA/RNA/protein world”), which was also facilitated by phagocytosis, horizontal gene transfer and different viral invasions87, 105.

 

Hereditics of the origin of life (the cell membrane and RNA)

The lipid cell membrane103 was a paramount factor in laying a foundation for LUCA to be the first form of life and heredity. For a long time, both RNA and DNA viruses were not included in the evolutionary history because they were considered nonliving entities. They were easily changed by the environment and they had no known origin105,108. Some procell experiments showed: “vesicles (of fatty acid) encapsulating high concentrations of RNA experienced substantial osmotic stress, driving the uptake of fatty acid”, including the ability to undergo multiple cycles of growth and division109. Thus, the cell membrane changed the fate of RNA and DNA by providing them a more stable internal environment (cytoplasm), with a more suitable temperature, moisture condition, and biochemical energy (by the capacity to concentrate macromolecules in pores)87,104. With evolution favoring a cell membrane that provided a stable environment, RNA and DNA genes began to replicate exponentially and, more precisely, began to be inherited to future generations by division. They no longer had high mutation rates across all replication systems to adapt to the external harsh environment9,104,108. The produced proteins would no longer be scattered everywhere without a prominent function. The proteins and RNA were concentrated enough by the surrounding cell membrane103, to allow DNA replication to be smooth, and to allow concentrated cytoskeletons to be formed naturally9 with its intrinsic polarity characteristics. Thus, the origin of life was the combination of RNA and cell membrane. The new establishment of the cytoskeletons vitalized LUCA cells as phagocytes that obtained mitochondria (to produce much more energy) and new genes for further evolution87,110. The cytoskeletons also made cell division, i.e. cell inheritance, possible. Further evolution of a second lipid membrane as a nucleus envelope in eukaryotes111 confirms that DNA prefers one more membrane to stabilize its internal environment for perfect replication.

 

Conclusion: New concepts for the study of heredity and future research

The common flawed theory of reproductive cloning, MRT, and PGS is based on the hypothesis that DNA is the unique hereditary material in human beings, and that the cytoplasm lacks heredity and differentiation functions. The data in this paper affirms that the cytoplasm is closely correlated to differentiation, heredity, and the origin of life. MRT severely damages three components of heredity: cell structure, cell division, and differentiation. Abnormal differentiation of cytoplasm will lead to abnormal function of organs and tissues. Abnormal ooplasm in MRT has produced MRT syndrome in MRT children. Laser radiation of cytoplasm and deformation of cytoplasm in PGS have also produced embryo biopsy syndrome (EB syndrome) in human offspring1. The exposed facts of MRT syndrome and EB syndrome confirm that MRT and PGS are neither scientific nor safe, and both will lead to subhuman reproduction112. The main aim of this paper is the prevention of subhuman reproduction by MRT, PGS, and any other artificial techniques that disturb the stability of the natural cytoplasm and genes in the human germline.

 

The history of life is a history of circles of evolution, natural selection, and heredity, which created all kinds of species of life in the world. Evolution is the relative change in heredity. Heredity is based on relatively stable genes and cell structures. Stability of heredity leads to the stability of species. According to history of evolution and recent developments in science, it is obvious that genes and DNA are the “software” and cytoplasm and cytoskeletons are the “hardware” of heredity. For laypeople, this can be understood as: only an intact whole egg (“yolk” and “white” together) may pass on heredity to the next generation. Damage of the said hereditary materials leads to damage of the stability of the said species. The stability of a good external environment and internal cellular environment may increase the stability of heredity, and may lower the variation of evolution and natural selection.

 

The above elucidation of how the cytoplasm is related to heredity, differentiation, and evolution, leads to several cardinal concepts: Hereditics, Cytohetics and epicytohetics. Research in the field of Cytohetics and Epicytohetics may be very helpful for the research of differentiation, cancer, many neuropathic diseases, immune diseases, and other system and organ diseases. Research of Hereditics will also allow understanding of new concepts in physiology, cellular biology, and many fields of life science.

References

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