Parthenogenesis is a natural form of asexual reproduction in which growth and development of embryos occur without fertilization. In animals, parthenogenesis means development of an embryo from an unfertilized egg cell. In plants parthenogenesis is a component process of apomixis. Parthenogenesis occurs in some plants, some invertebrate animal species and a few vertebrates; this type of reproduction has been induced artificially in a few species including fish and amphibians. Normal egg cells form after meiosis and are haploid, with half as many chromosomes as their mother's body cells. Haploid individuals, are non-viable, parthenogenetic offspring have the diploid chromosome number. Depending on the mechanism involved in restoring the diploid number of chromosomes, parthenogenetic offspring may have anywhere between all and half of the mother's alleles; the offspring having all of the mother's genetic material are called full clones and those having only half are called half clones. Full clones are formed without meiosis.
If meiosis occurs, the offspring will get only a fraction of the mother's alleles since crossing over of DNA takes place during meiosis, creating variation. Parthenogenetic offspring in species that use either the XY or the X0 sex-determination system have two X chromosomes and are female. In species that use the ZW sex-determination system, they have either two Z chromosomes or two W chromosomes, or they could have one Z and one W chromosome; some species reproduce by parthenogenesis, while others can switch between sexual reproduction and parthenogenesis. This is called facultative parthenogenesis; the switch between sexuality and parthenogenesis in such species may be triggered by the season, or by a lack of males or by conditions that favour rapid population growth. In these species asexual reproduction occurs either in summer or as long as conditions are favourable; this is because in asexual reproduction a successful genotype can spread without being modified by sex or wasting resources on male offspring who won't give birth.
In times of stress, offspring produced by sexual reproduction may be fitter as they have new beneficial gene combinations. In addition, sexual reproduction provides the benefit of meiotic recombination between non-sister chromosomes, a process associated with repair of DNA double-strand breaks and other DNA damages that may be induced by stressful conditions. Many taxa with heterogony have within them species that have lost the sexual phase and are now asexual. Many other cases of obligate parthenogenesis are found among polyploids and hybrids where the chromosomes cannot pair for meiosis; the production of female offspring by parthenogenesis is referred to as thelytoky while the production of males by parthenogenesis is referred to as arrhenotoky. When unfertilized eggs develop into both males and females, the phenomenon is called deuterotoky. Parthenogenesis can occur without meiosis through mitotic oogenesis; this is called apomictic parthenogenesis. Mature egg cells are produced by mitotic divisions, these cells directly develop into embryos.
In flowering plants, cells of the gametophyte can undergo this process. The offspring produced by apomictic parthenogenesis are full clones of their mother. Examples include aphids. Parthenogenesis involving meiosis is more complicated. In some cases, the offspring are haploid. In other cases, collectively called automictic parthenogenesis, the ploidy is restored to diploidy by various means; this is. In automictic parthenogenesis, the offspring differ from their mother, they are called half clones of their mother. Automixis is a term. Diploidy might be restored by the doubling of the chromosomes without cell division before meiosis begins or after meiosis is completed; this is referred to as an endomitotic cycle. This may happen by the fusion of the first two blastomeres. Other species restore their ploidy by the fusion of the meiotic products; the chromosomes may not separate at one of the two anaphases or the nuclei produced may fuse or one of the polar bodies may fuse with the egg cell at some stage during its maturation.
Some authors consider all forms of automixis sexual. Many others classify the endomitotic variants as asexual and consider the resulting embryos parthenogenetic. Among these authors, the threshold for classifying automixis as a sexual process depends on when the products of anaphase I or of anaphase II are joined together; the criterion for "sexuality" varies from all cases of restitutional meiosis, to those where the nuclei fuse or to only those where gametes are mature at the time of fusion. Those cases of automixis that are classified as sexual reproduction are compared to self-fertilization in their mechanism and consequences; the genetic composition of the offspring depends on. When endomitosis occurs before meiosis or when central fusion occurs, the offspring get all to mor
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubules; these cells are called spermatogonial stem cells. The mitotic division of these produces two types of cells. Type A cells replenish the stem cells, type B cells differentiate into spermatocytes; the primary spermatocyte divides meiotically into two secondary spermatocytes. The spermatids are transformed into spermatozoa by the process of spermiogenesis; these develop into mature spermatozoa known as sperm cells. Thus, the primary spermatocyte gives rise to two cells, the secondary spermatocytes, the two secondary spermatocytes by their subdivision produce four spermatozoa and four haploid cells. Spermatozoa are the mature male gametes in many sexually reproducing organisms. Thus, spermatogenesis is the male version of gametogenesis, of which the female equivalent is oogenesis.
In mammals it occurs in the seminiferous tubules of the male testes in a stepwise fashion. Spermatogenesis is dependent upon optimal conditions for the process to occur and is essential for sexual reproduction. DNA methylation and histone modification have been implicated in the regulation of this process, it starts at puberty and continues uninterrupted until death, although a slight decrease can be discerned in the quantity of produced sperm with increase in age. Spermatogenesis produces mature male gametes called sperm but more known as spermatozoa, which are able to fertilize the counterpart female gamete, the oocyte, during conception to produce a single-celled individual known as a zygote; this is the cornerstone of sexual reproduction and involves the two gametes both contributing half the normal set of chromosomes to result in a chromosomally normal zygote. To preserve the number of chromosomes in the offspring – which differs between species – one of each gamete must have half the usual number of chromosomes present in other body cells.
Otherwise, the offspring will have twice the normal number of chromosomes, serious abnormalities may result. In humans, chromosomal abnormalities arising from incorrect spermatogenesis results in congenital defects and abnormal birth defects and in most cases, spontaneous abortion of the developing foetus. Spermatogenesis takes place within several structures of the male reproductive system; the initial stages occur within the testes and progress to the epididymis where the developing gametes mature and are stored until ejaculation. The seminiferous tubules of the testes are the starting point for the process, where spermatogonial stem cells adjacent to the inner tubule wall divide in a centripetal direction—beginning at the walls and proceeding into the innermost part, or lumen—to produce immature sperm. Maturation occurs in the epididymis; the location is important as the process of spermatogenesis requires a lower temperature to produce viable sperm 1°-8 °C lower than normal body temperature of 37 °C.
Clinically, small fluctuations in temperature such as from an athletic support strap, causes no impairment in sperm viability or count. For humans, the entire process of spermatogenesis is variously estimated as taking 74 days and 120 days. Including the transport on ductal system, it takes 3 months. Testes produce 200 to 300 million spermatozoa daily. However, only about half or 100 million of these become viable sperm; the entire process of spermatogenesis can be broken up into several distinct stages, each corresponding to a particular type of cell in humans. In the following table, copy number and chromosome/chromatid counts are for one cell prior to DNA synthesis and division; the primary spermatocyte is arrested after DNA synthesis and prior to division. Spermatocytogenesis is the male form of gametocytogenesis and results in the formation of spermatocytes possessing half the normal complement of genetic material. In spermatocytogenesis, a diploid spermatogonium, which resides in the basal compartment of the seminiferous tubules, divides mitotically, producing two diploid intermediate cells called primary spermatocytes.
Each primary spermatocyte moves into the adluminal compartment of the seminiferous tubules and duplicates its DNA and subsequently undergoes meiosis I to produce two haploid secondary spermatocytes, which will divide once more into haploid spermatids. This division implicates sources of genetic variation, such as random inclusion of either parental chromosomes, chromosomal crossover that increases the genetic variability of the gamete; the DNA damage response machinery plays an important role in spermatogenesis. The protein FMRP binds to meiotic chromosomes and regulates the dynamics of the DDR machinery during spermatogenesis. FMRP appears to be necessary for the repair of DNA damage; each cell division from a spermatogonium to a spermatid is incomplete. It should be noted that not all spermatogonia divide to produce spermatocytes. Instead, spermatogonial stem cells divide mitotically to produce copies of themselves, ensuring a constant supply of spermatogonia to fuel spermatogenesis. Spermatidogenesis is the creation of spermatids from secondary spermatocytes.
Secondary spermatocytes produced earlie
Sponges, the members of the phylum Porifera, are a basal Metazoa clade as a sister of the Diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through them, consisting of jelly-like mesohyl sandwiched between two thin layers of cells; the branch of zoology that studies sponges is known as spongiology. Sponges have unspecialized cells that can transform into other types and that migrate between the main cell layers and the mesohyl in the process. Sponges do not have digestive or circulatory systems. Instead, most rely on maintaining a constant water flow through their bodies to obtain food and oxygen and to remove wastes. Sponges were first to branch off the evolutionary tree from the common ancestor of all animals, making them the sister group of all other animals; the term sponge derives from the Ancient Greek word σπόγγος. Sponges are similar to other animals in that they are multicellular, lack cell walls and produce sperm cells.
Unlike other animals, they lack true organs. Some of them are radially symmetrical; the shapes of their bodies are adapted for maximal efficiency of water flow through the central cavity, where it deposits nutrients, leaves through a hole called the osculum. Many sponges have internal skeletons of spongin and/or spicules of calcium carbonate or silicon dioxide. All sponges are sessile aquatic animals. Although there are freshwater species, the great majority are marine species, ranging from tidal zones to depths exceeding 8,800 m. While most of the 5,000–10,000 known species feed on bacteria and other food particles in the water, some host photosynthesizing microorganisms as endosymbionts and these alliances produce more food and oxygen than they consume. A few species of sponge that live in food-poor environments have become carnivores that prey on small crustaceans. Most species use sexual reproduction, releasing sperm cells into the water to fertilize ova that in some species are released and in others are retained by the "mother".
The fertilized eggs form larvae to settle. Sponges are known for regenerating from fragments that are broken off, although this only works if the fragments include the right types of cells. A few species reproduce by budding; when conditions deteriorate, for example as temperatures drop, many freshwater species and a few marine ones produce gemmules, "survival pods" of unspecialized cells that remain dormant until conditions improve and either form new sponges or recolonize the skeletons of their parents. The mesohyl functions as an endoskeleton in most sponges, is the only skeleton in soft sponges that encrust hard surfaces such as rocks. More the mesohyl is stiffened by mineral spicules, by spongin fibers or both. Demosponges use spongin, in many species, silica spicules and in some species, calcium carbonate exoskeletons. Demosponges constitute about 90% of all known sponge species, including all freshwater ones, have the widest range of habitats. Calcareous sponges, which have calcium carbonate spicules and, in some species, calcium carbonate exoskeletons, are restricted to shallow marine waters where production of calcium carbonate is easiest.
The fragile glass sponges, with "scaffolding" of silica spicules, are restricted to polar regions and the ocean depths where predators are rare. Fossils of all of these types have been found in rocks dated from 580 million years ago. In addition Archaeocyathids, whose fossils are common in rocks from 530 to 490 million years ago, are now regarded as a type of sponge; the single-celled choanoflagellates resemble the choanocyte cells of sponges which are used to drive their water flow systems and capture most of their food. This along with phylogenetic studies of ribosomal molecules have been used as morphological evidence to suggest sponges are the sister group to the rest of animals; some studies have shown that sponges do not form a monophyletic group, in other words do not include all and only the descendants of a common ancestor. Recent phylogenetic analyses suggest that comb jellies rather than sponges are the sister group to the rest of animals; the few species of demosponge that have soft fibrous skeletons with no hard elements have been used by humans over thousands of years for several purposes, including as padding and as cleaning tools.
By the 1950s, these had been overfished so that the industry collapsed, most sponge-like materials are now synthetic. Sponges and their microscopic endosymbionts are now being researched as possible sources of medicines for treating a wide range of diseases. Dolphins have been observed using sponges as tools while foraging. Sponges constitute the phylum Porifera, have been defined as sessile metazoans that have water intake and outlet openings connected by chambers lined with choanocytes, cells with whip-like flagella. However, a few carnivorous sponges have lost the choanocytes. All known living sponges can remold their bodies, as most types of their cells can move within their bodies and a few can change from one type to another. If a few sponges are able to produce mucus – which acts as a microbial barrier in all other animals – no sponge with the ability to secrete a functional mucus layer has been recorded. Without such a mucus layer their living tissue is covered by a layer of microbial symbionts, which can contribute up to 40–50% of the sponge wet mass.
This inability to prevent microbes from penetrating their porous tissue could be a major reason why they have never evolved a more complex anatomy. Like cnidarians (jellyfish, e
Cell potency is a cell's ability to differentiate into other cell types. The more cell types. Potency is described as the gene activation potential within a cell, which like a continuum, begins with totipotency to designate a cell with the most differentiation potential, multipotency and unipotency. Totipotency is the ability of a single cell to divide and produce all of the differentiated cells in an organism. Spores and zygotes are examples of totipotent cells. In the spectrum of cell potency, totipotency represents the cell with the greatest differentiation potential, being able to differentiate into any embryonic cell, as well as extraembryonic cells. In contrast, pluripotent cells can only differentiate into embryonic cells, it is possible for a differentiated cell to return to a state of totipotency. This conversion to totipotency is complex, not understood and the subject of recent research. Research in 2011 has shown that cells may differentiate not into a totipotent cell, but instead into a "complex cellular variation" of totipotency.
Stem cells resembling totipotent blastomeres from 2-cell stage embryos can arise spontaneously in mouse embryonic stem cell cultures and can be induced to arise more in vitro through down-regulation of the chromatin assembly activity of CAF-1. The human development model is one. Human development begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote. In the first hours after fertilization, this zygote divides into identical totipotent cells, which can develop into any of the three germ layers of a human, or into cells of the placenta. After reaching a 16-cell stage, the totipotent cells of the morula differentiate into cells that will become either the blastocyst's Inner cell mass or the outer trophoblasts. Four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize; the inner cell mass, the source of embryonic stem cells, becomes pluripotent. Research on Caenorhabditis elegans suggests that multiple mechanisms including RNA regulation may play a role in maintaining totipotency at different stages of development in some species.
Work with zebrafish and mammals suggest a further interplay between miRNA and RNA-binding proteins in determining development differences. In mouse primordial germ cells, genome-wide reprogramming leading to totipotency involves erasure of epigenetic imprints. Reprogramming is facilitated by active DNA demethylation involving the DNA base excision repair enzymatic pathway; this pathway entails erasure of CpG methylation in primordial germ cells via the initial conversion of 5mC to 5-hydroxymethylcytosine, a reaction driven by high levels of the ten-eleven dioxygenase enzymes TET-1 and TET-2. In cell biology, pluripotency refers to a stem cell that has the potential to differentiate into any of the three germ layers: endoderm, mesoderm, or ectoderm. However, cell pluripotency is a continuum, ranging from the pluripotent cell that can form every cell of the embryo proper, e.g. embryonic stem cells and iPSCs, to the incompletely or pluripotent cell that can form cells of all three germ layers but that may not exhibit all the characteristics of pluripotent cells.
Induced pluripotent stem cells abbreviated as iPS cells or iPSCs, are a type of pluripotent stem cell artificially derived from a non-pluripotent cell an adult somatic cell, by inducing a "forced" expression of certain genes and transcription factors. These transcription factors play a key role in determining the state of these cells and highlights the fact that these somatic cells do preserve the same genetic information as early embryonic cells; the ability to induce cells into a pluripotent state was pioneered in 2006 using mouse fibroblasts and four transcription factors, Oct4, Sox2, Klf4 and c-Myc. This was followed in 2007 by the successful induction of human iPSCs derived from human dermal fibroblasts using methods similar to those used for the induction of mouse cells; these induced cells exhibit similar traits to those of embryonic stem cells but do not require the use of embryos. Some of the similarities between ESCs and iPSCs include pluripotency, self-renewal ability, a trait that implies that they can divide and replicate indefinitely, gene expression.
Epigenetic factors are thought to be involved in the actual reprogramming of somatic cells in order to induce pluripotency. It has been theorized that certain epigenetic factors might work to clear the original somatic epigenetic marks in order to acquire the new epigenetic marks that are part of achieving a pluripotent state. Chromatin is reorganized in iPSCs and becomes like that found in ESCs in that it is less condensed and therefore more accessible. Euchromatin modifications are common, consistent with the state of euchromatin found in ESCs. Due to their great similarity to ESCs, iPSCs have been of great interest to the medical and research community. IPSCs could have the same therapeutic implications and applications as ESCs but without the controversial use of embryos
Cellular differentiation is the process where a cell changes from one cell type to another. The cell changes to a more specialized type. Differentiation occurs numerous times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create differentiated daughter cells during tissue repair and during normal cell turnover; some differentiation occurs in response to antigen exposure. Differentiation changes a cell's size, membrane potential, metabolic activity, responsiveness to signals; these changes are due to controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation never involves a change in the DNA sequence itself. Thus, different cells can have different physical characteristics despite having the same genome. A specialized type of differentiation, known as'terminal differentiation', is of importance in some tissues, for example vertebrate nervous system, striated muscle and gut.
During terminal differentiation, a precursor cell capable of cell division, permanently leaves the cell cycle, dismantles the cell cycle machinery and expresses a range of genes characteristic of the cell's final function. Differentiation may continue to occur after terminal differentiation if the capacity and functions of the cell undergo further changes. Among dividing cells, there are multiple levels of cell potency, the cell's ability to differentiate into other cell types. A greater potency indicates a larger number of cell types. A cell that can differentiate into all cell types, including the placental tissue, is known as totipotent. In mammals, only the zygote and subsequent blastomeres are totipotent, while in plants, many differentiated cells can become totipotent with simple laboratory techniques. A cell that can differentiate into all cell types of the adult organism is known as pluripotent; such cells are called meristematic cells in higher plants and embryonic stem cells in animals, though some groups report the presence of adult pluripotent cells.
Virally induced expression of four transcription factors Oct4, Sox2, c-Myc, KIF4 is sufficient to create pluripotent cells from adult fibroblasts. A multipotent cell is one that can differentiate into multiple different, but related cell types. Oligopotent cells are more restricted than multipotent, but can still differentiate into a few related cell types. Unipotent cells can differentiate into only one cell type, but are capable of self-renewal. In cytopathology, the level of cellular differentiation is used as a measure of cancer progression. "Grade" is a marker of. Three basic categories of cells make up the mammalian body: germ cells, somatic cells, stem cells; each of the 37.2 trillion cells in an adult human has its own copy or copies of the genome except certain cell types, such as red blood cells, that lack nuclei in their differentiated state. Most cells are diploid; such cells, called somatic cells, make up most such as skin and muscle cells. Cells differentiate to specialize for different functions.
Germ line cells are any line of cells that give rise to gametes—eggs and sperm—and thus are continuous through the generations. Stem cells, on the other hand, have the ability to divide for indefinite periods and to give rise to specialized cells, they are best described in the context of normal human development. Development begins when a sperm fertilizes an egg and creates a single cell that has the potential to form an entire organism. In the first hours after fertilization, this cell divides into identical cells. In humans four days after fertilization and after several cycles of cell division, these cells begin to specialize, forming a hollow sphere of cells, called a blastocyst; the blastocyst has an outer layer of cells, inside this hollow sphere, there is a cluster of cells called the inner cell mass. The cells of the inner cell mass go on to form all of the tissues of the human body. Although the cells of the inner cell mass can form every type of cell found in the human body, they cannot form an organism.
These cells are referred to as pluripotent. Pluripotent stem cells undergo further specialization into multipotent progenitor cells that give rise to functional cells. Examples of stem and progenitor cells include: Radial glial cells that give rise to excitatory neurons in the fetal brain through the process of neurogenesis. Hematopoietic stem cells from the bone marrow that give rise to red blood cells, white blood cells, platelets Mesenchymal stem cells from the bone marrow that give rise to stromal cells, fat cells, types of bone cells Epithelial stem cells that give rise to the various types of skin cells Muscle satellite cells that contribute to differentiated muscle tissue. A pathway, guided by the cell adhesion molecules consisting of four amino acids, glycine and serine, is created as the cellular blastomere differentiates from the single-layered blastula to the three primary layers of germ cells in mammals, namely the ectoderm and endoderm; the ectoderm ends up forming the skin and the nervous system, the mesoderm forms the bones and muscular tissue, the endoderm forms the internal organ tissues.
Stem cells are cells that can differentiate into other types of cells, can divide in self-renewal to produce more of the same type of stem cells. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts in early embryonic development, adult stem cells, which are found in various tissues of developed mammals. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm and mesoderm —but maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. There are three known accessible sources of autologous adult stem cells in humans: bone marrow, adipose tissue, blood. Stem cells can be taken from umbilical cord blood just after birth. Of all stem cell therapy types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures.
Adult stem cells are used in various medical therapies. Stem cells can now be artificially grown and transformed into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through somatic cell nuclear transfer or dedifferentiation have been proposed as promising candidates for future therapies. Research into stem cells grew out of findings by Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s; the classical definition of a stem cell requires that it possesses two properties: Self-renewal: the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. Potency: the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent—to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells.
Apart from this it is said. Two mechanisms ensure that a stem cell population is maintained: 1. Obligatory asymmetric replication: a stem cell divides into one mother cell, identical to the original stem cell, another daughter cell, differentiated; when a stem cell self-renews it does not disrupt the undifferentiated state. This self-renewal demands control of cell cycle as well as upkeep of multipotency or pluripotency, which all depends on the stem cell.2. Stochastic differentiation: when one stem cell develops into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem cells identical to the original. Potency specifies the differentiation potential of the stem cell. Totipotent stem cells can differentiate into extraembryonic cell types; such cells can construct a viable organism. These cells are produced from the fusion of an sperm cell. Cells produced by the first few divisions of the fertilized egg are totipotent. Pluripotent stem cells are the descendants of totipotent cells and can differentiate into nearly all cells, i.e. cells derived from any of the three germ layers.
Multipotent stem cells can differentiate into a number of cell types, but only those of a related family of cells. Oligopotent stem cells can differentiate into only a few cell types, such as lymphoid or myeloid stem cells. Unipotent cells can produce only one cell type, their own, but have the property of self-renewal, which distinguishes them from non-stem cells. In practice, stem cells are identified by. For example, the defining test for bone marrow or hematopoietic stem cells is the ability to transplant the cells and save an individual without HSCs; this demonstrates. It should be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew. Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew. Stem cells can be isolated by their possession of a distinctive set of cell surface markers.
However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells shall behave in a similar manner in vivo. There is considerable debate as to whether some proposed adult cell populations are stem cells. Embryonic stem cells are the cells of the inner cell mass of a blastocyst, formed prior to implantation in the uterus. In human embryonic development the blastocyst stage is reached 4–5 days after fertilization, at which time it consists of 50–150 cells. ESCs are pluripotent and give rise during development to all derivatives of the three germ layers: ectoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type, they do not contribute to the placenta. During embryonic development the cells of the inner cell mass continuously divide and become more specialized. For example, a portion of the ectoderm in the dorsal part of the embryo specializes as'neurectoderm', which
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the basis for biological inheritance; the cell possesses the distinctive property of division. DNA is made up of a double helix of two complementary strands. During replication, these strands are separated; each strand of the original DNA molecule serves as a template for the production of its counterpart, a process referred to as semiconservative replication. As a result of semi-conservative replication, the new helix will be composed of an original DNA strand as well as a newly synthesized strand. Cellular proofreading and error-checking mechanisms ensure near perfect fidelity for DNA replication. In a cell, DNA replication begins at origins of replication, in the genome. Unwinding of DNA at the origin and synthesis of new strands, accommodated by an enzyme known as helicase, results in replication forks growing bi-directionally from the origin.
A number of proteins are associated with the replication fork to help in the initiation and continuation of DNA synthesis. Most prominently, DNA polymerase synthesizes the new strands by adding nucleotides that complement each strand. DNA replication occurs during the S-stage of interphase. DNA replication can be performed in vitro. DNA polymerases isolated from cells and artificial DNA primers can be used to start DNA synthesis at known sequences in a template DNA molecule. Polymerase chain reaction, ligase chain reaction, transcription-mediated amplification are examples. DNA exists as a double-stranded structure, with both strands coiled together to form the characteristic double-helix; each single strand of DNA is a chain of four types of nucleotides. Nucleotides in DNA contain a deoxyribose sugar, a phosphate, a nucleobase; the four types of nucleotide correspond to the four nucleobases adenine, cytosine and thymine abbreviated as A, C, G and T. Adenine and guanine are purine bases, while cytosine and thymine are pyrimidines.
These nucleotides form phosphodiester bonds, creating the phosphate-deoxyribose backbone of the DNA double helix with the nucleobases pointing inward. Nucleobases are matched between strands through hydrogen bonds to form base pairs. Adenine pairs with thymine, guanine pairs with cytosine. DNA strands have a directionality, the different ends of a single strand are called the "3′ end" and the "5′ end". By convention, if the base sequence of a single strand of DNA is given, the left end of the sequence is the 5′ end, while the right end of the sequence is the 3′ end; the strands of the double helix are anti-parallel with one being 5′ to 3′, the opposite strand 3′ to 5′. These terms refer to the carbon atom in deoxyribose to which the next phosphate in the chain attaches. Directionality has consequences in DNA synthesis, because DNA polymerase can synthesize DNA in only one direction by adding nucleotides to the 3′ end of a DNA strand; the pairing of complementary bases in DNA means that the information contained within each strand is redundant.
Phosphodiester bonds are stronger than hydrogen bonds. This allows the strands to be separated from one another; the nucleotides on a single strand can therefore be used to reconstruct nucleotides on a newly synthesized partner strand. DNA polymerases are a family of enzymes. DNA polymerases in general cannot initiate synthesis of new strands, but can only extend an existing DNA or RNA strand paired with a template strand. To begin synthesis, a short fragment of RNA, called a primer, must be created and paired with the template DNA strand. DNA polymerase adds a new strand of DNA by extending the 3′ end of an existing nucleotide chain, adding new nucleotides matched to the template strand one at a time via the creation of phosphodiester bonds; the energy for this process of DNA polymerization comes from hydrolysis of the high-energy phosphate bonds between the three phosphates attached to each unincorporated base. Free bases with their attached phosphate groups are called nucleotides; when a nucleotide is being added to a growing DNA strand, the formation of a phosphodiester bond between the proximal phosphate of the nucleotide to the growing chain is accompanied by hydrolysis of a high-energy phosphate bond with release of the two distal phosphates as a pyrophosphate.
Enzymatic hydrolysis of the resulting pyrophosphate into inorganic phosphate consumes a second high-energy phosphate bond and renders the reaction irreversible. In general, DNA polymerases are accurate, with an intrinsic error rate of less than one mistake for every 107 nucleotides added. In addition, some DNA polymerases have proofreading ability. Post-replication mismatch repair mechanisms monitor the DNA for errors, being capable of distinguishing mismatches in the newly synthesized DNA strand from the original strand sequence. Together, these three discrimination steps enable replication fidelity of less than one mistake for every 109 nucleotides added; the rate of DNA replication in a living cell was first measured as the rate of phage T4 DNA elongation in phage-infected E. coli. During the period of exponential DNA increase at 37 °C, the rate was 749 nucleotides per second