Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes within and relating to living organisms. Biochemical processes give rise to the complexity of life. A sub-discipline of both biology and chemistry, biochemistry can be divided in three fields. Over the last decades of the 20th century, biochemistry has through these three disciplines become successful at explaining living processes. All areas of the life sciences are being uncovered and developed by biochemical methodology and research. Biochemistry focuses on understanding how biological molecules give rise to the processes that occur within living cells and between cells, which in turn relates to the study and understanding of tissues and organism structure and function. Biochemistry is related to molecular biology, the study of the molecular mechanisms by which genetic information encoded in DNA is able to result in the processes of life. Much of biochemistry deals with the structures and interactions of biological macromolecules, such as proteins, nucleic acids and lipids, which provide the structure of cells and perform many of the functions associated with life.
The chemistry of the cell depends on the reactions of smaller molecules and ions. These can be inorganic, for example water and metal ions, or organic, for example the amino acids, which are used to synthesize proteins; the mechanisms by which cells harness energy from their environment via chemical reactions are known as metabolism. The findings of biochemistry are applied in medicine and agriculture. In medicine, biochemists investigate the cures of diseases. In nutrition, they study how to maintain health wellness and study the effects of nutritional deficiencies. In agriculture, biochemists investigate soil and fertilizers, try to discover ways to improve crop cultivation, crop storage and pest control. At its broadest definition, biochemistry can be seen as a study of the components and composition of living things and how they come together to become life, in this sense the history of biochemistry may therefore go back as far as the ancient Greeks. However, biochemistry as a specific scientific discipline has its beginning sometime in the 19th century, or a little earlier, depending on which aspect of biochemistry is being focused on.
Some argued that the beginning of biochemistry may have been the discovery of the first enzyme, diastase, in 1833 by Anselme Payen, while others considered Eduard Buchner's first demonstration of a complex biochemical process alcoholic fermentation in cell-free extracts in 1897 to be the birth of biochemistry. Some might point as its beginning to the influential 1842 work by Justus von Liebig, Animal chemistry, or, Organic chemistry in its applications to physiology and pathology, which presented a chemical theory of metabolism, or earlier to the 18th century studies on fermentation and respiration by Antoine Lavoisier. Many other pioneers in the field who helped to uncover the layers of complexity of biochemistry have been proclaimed founders of modern biochemistry, for example Emil Fischer for his work on the chemistry of proteins, F. Gowland Hopkins on enzymes and the dynamic nature of biochemistry; the term "biochemistry" itself is derived from a combination of chemistry. In 1877, Felix Hoppe-Seyler used the term as a synonym for physiological chemistry in the foreword to the first issue of Zeitschrift für Physiologische Chemie where he argued for the setting up of institutes dedicated to this field of study.
The German chemist Carl Neuberg however is cited to have coined the word in 1903, while some credited it to Franz Hofmeister. It was once believed that life and its materials had some essential property or substance distinct from any found in non-living matter, it was thought that only living beings could produce the molecules of life. In 1828, Friedrich Wöhler published a paper on the synthesis of urea, proving that organic compounds can be created artificially. Since biochemistry has advanced since the mid-20th century, with the development of new techniques such as chromatography, X-ray diffraction, dual polarisation interferometry, NMR spectroscopy, radioisotopic labeling, electron microscopy, molecular dynamics simulations; these techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle, led to an understanding of biochemistry on a molecular level. Philip Randle is well known for his discovery in diabetes research is the glucose-fatty acid cycle in 1963.
He confirmed. High fat oxidation was responsible for the insulin resistance. Another significant historic event in biochemistry is the discovery of the gene, its role in the transfer of information in the cell; this part of biochemistry is called molecular biology. In the 1950s, James D. Watson, Francis Crick, Rosalind Franklin, Maurice Wilkins were instrumental in solving DNA structure and suggesting its relationship with genetic transfer of information. In 1958, George Beadle and Edward Tatum received the Nobel Prize for work in fungi showing that one gene produces one enzyme. In 1988, Colin Pitchfork was the first person convicted of murder with DNA evidence, which led to the growth of forensic science. More Andrew Z. Fire and Craig C. Mello received the 2006 Nobel Prize for discovering the role of RNA interference, in the silencing of gene expression. Around two dozen of the 92
Asexual reproduction
Asexual reproduction is a type of reproduction by which offspring arise from a single organism, inherit the genes of that parent only. Asexual reproduction is the primary form of reproduction for single-celled organisms such as archaea and bacteria. Many plants and fungi sometimes reproduce asexually; some Asexual cells die when they are young. While all prokaryotes reproduce without the formation and fusion of gametes, mechanisms for lateral gene transfer such as conjugation and transduction can be likened to sexual reproduction in the sense of genetic recombination in meiosis. A complete lack of sexual reproduction is rare among multi-cellular organisms animals, it is not understood why the ability to reproduce sexually is so common among them. Current hypotheses suggest that asexual reproduction may have short term benefits when rapid population growth is important or in stable environments, while sexual reproduction offers a net advantage by allowing more rapid generation of genetic diversity, allowing adaptation to changing environments.
Developmental constraints may underlie why few animals have relinquished sexual reproduction in their life-cycles. Another constraint on switching from sexual to asexual reproduction would be the concomitant loss of meiosis and the protective recombinational repair of DNA damage afforded as one function of meiosis. An important form of fission is binary fission, where the parent organism is replaced by two daughter organisms, because it divides in two. Only prokaryotes reproduce asexually through binary fission. Eukaryotes may reproduce in a functionally similar manner by mitosis. Many Asexual cells die off. Multiple fission at the cellular level occurs in e.g. sporozoans and algae. The nucleus of the parent cell divides several times by mitosis; the cytoplasm separates, creating multiple daughter cells. In apicomplexans, multiple fission, or schizogony appears either as merogony, sporogony or gametogony. Merogony results in merozoites, which are multiple daughter cells, that originate within the same cell membrane, sporogony results in sporozoites, gametogony results in microgametes.
Some cells split via budding. The offspring organism is smaller than the parent. Budding is known on a multi-cellular level; the buds grow into matured individuals which break away from the parent organism. Internal budding is a process of asexual reproduction, favoured by parasites such as Toxoplasma gondii, it involves an unusual process in which two or more daughter cells are produced inside a mother cell, consumed by the offspring prior to their separation. Budding is present in some worm like Taenia or Echinococci. Vegetative propagation is a type of asexual reproduction found in plants where new individuals are formed without the production of seeds or spores by meiosis or syngamy. Examples of vegetative reproduction include the formation of miniaturized plants called plantlets on specialized leaves and some produce new plants out of rhizomes or stolon. Other plants reproduce by forming tubers; some plants produce adventitious shoots and may form a clonal colony, where all the individuals are clones, the clones may cover a large area.
Many multi-cellular organisms form spores during their biological life cycle in a process called sporogenesis. Exceptions are animals and some protists, who undergo meiosis followed by fertilization. Plants and many algae on the other hand undergo sporic meiosis where meiosis leads to the formation of haploid spores rather than gametes; these spores grow into multi-cellular individuals without a fertilization event. These haploid individuals give rise to gametes through mitosis. Meiosis and gamete formation therefore occur in separate generations or "phases" of the life cycle, referred to as alternation of generations. Since sexual reproduction is more narrowly defined as the fusion of gametes, spore formation in plant sporophytes and algae might be considered a form of asexual reproduction despite being the result of meiosis and undergoing a reduction in ploidy. However, both events are necessary to complete sexual reproduction in the plant life cycle. Fungi and some algae can utilize true asexual spore formation, which involves mitosis giving rise to reproductive cells called mitospores that develop into a new organism after dispersal.
This method of reproduction is found for example in conidial fungi and the red algae Polysiphonia, involves sporogenesis without meiosis. Thus the chromosome number of the spore cell is the same as that of the parent producing the spores. However, mitotic sporogenesis is an exception and most spores, such as those of plants, most Basidiomycota, many algae, are produced by meiosis. Fragmentation is a form of asexual reproduction where a new organism grows from a fragment of the parent; each fragment develops into a mature grown individual. Fragmentation is seen in many organisms. Animals that reproduce asexually include planarians, many annelid worms including polychaetes and
Sarcocystis
Sarcocystis is a genus of parasites, the majority of species infecting mammals, some infecting reptiles and birds. The life-cycle of a typical member of this genus involves two host species, a definitive host and an intermediate host; the definitive host is a predator and the intermediate host is its prey. The parasite reproduces sexually in the gut of the definitive host, is passed with the feces and ingested by the intermediate host. There it enters muscle tissue; when the intermediate host is eaten by the definitive host, the cycle is completed. The definitive host does not show any symptoms of infection, but the intermediate host does. There are about 130 recognized species in this genus. Revision of the taxonomy of the genus is ongoing, it is possible that all the recognised species may in fact be a much smaller number of species that can infect multiple hosts; the name Sarcocystis is dervived from Greek: sarx = flesh and kystis = bladder. The organism was first recognised in a mouse by Miescher in 1843.
His findings were not interpreted as involving a protist, the literature referred to the structures he described as "Miescher's Tubules". Incidentally, Miescher's son — Johann Friedrich Miescher — discovered DNA. Similar structures were found in pig muscle in 1865 but these remained unnamed until 1899, when the name Sarcocystis miescheriana was proposed for them, it was unclear whether these organisms were fungi or protozoa. This uncertainty was resolved in 1967 when electron microscopic studies showed that they were protozoa, related to Toxoplasma and Eimeria; the life cycle remained unknown until 1970, when bradyzoites from sarcocysts in bird muscles were inoculated into cultured mammalian cells and seen to undergo development into sexual stages and oocysts. Transmission studies with Sarcocystis of cattle in dogs and humans revealed three morphologically distinct species, which were named Sarcocystis bovicanis, Sarcocystis bovifelis and Sarcocystis bovihominis; this and post-1972 research on Sarcocystis was reviewed during the same decade.
The coverage of concepts in this review chapter is broader than reflected by its title and much of the important information therein does not appear in more recent publications. The heteroxenous life cycle of these apicomplexan parasites remained obscure until 1972, when the prey-predator relationship of its definitive and intermediate hosts was recognised; the life cycle of about 60 of these species is now known. In outline gametogony and sporogony occur in the intestine of the definitive host while both schizogony which occurs in various tissues and the formation of sarcocysts occurs principally in the muscles of the intermediate host. In some cases a single species may act as both the intermediate host. Oocysts are passed in the feces of an infected definitive host; the oocyst undergoes sporogony creating two sporocysts. Once this is complete the oocyst itself undergoes lysis releasing the sporocysts into the environment. Sporocysts contain 4 sporozoites and measure 15-19 by 8-10 micrometres.
An intermediate host such as a cow or pig ingests a sporocyst. Sporozoites are released in the body and migrate to vessels where they undergo the first two generation of asexual reproduction; these rounds result in the development of meronts. This stage lasts about 15 to 16 days after ingestion of sporocysts. Merozoites emerge from the second generation meronts and enter the mononucleate cells where they develop by endodyogeny. Subsequent generations of merozoites develop downstream in the direction of blood flow to arterioles, capillaries and veins throughout the body subsequently developing into the final asexual generation in muscles. Merozoites entering muscle cells round up to initiate sarcocyst formation. Sarcocysts begin as unicellular bodies containing a single metrocyte and through asexual multiplication numerous metrocytes accumulate and the sarcocyst increases in size; as the sarcocyst matures, the small, noninfectious metrocytes give rise to crescent-shaped bodies called bradyzoites that are infectious for the definitive host.
The time required for maturation may take 2 months or more. In species in which symptoms develop these occur 20–40 days after ingestion of sporocysts and during the subsequent migration of sporozoites through the body vessels. Acute lesions develop in the affected tissues; the parasite has a predilection for skeletal muscle, cardiac muscle, lymph nodes. These lesions are associated with maturation of second generation of meronts within the endothelial and subendothelials cells. Mononuclear infiltration or hyperemia has been observed in the lamina propria of the small intestine. After the acute phase cysts may be found in various muscular tissues without pathology. Once the intermediate host is eaten by the definitive host such as a dog or human, the parasite undergoes sexual reproduction within the gut to create macrogamonts and microgamonts. Most definitive hosts do not show symptoms. Fusion of a macrogamont and a microgamont creates a zygote; the oocyst is passed through the faeces completing the life cycle.
A second life cycle has more been described whereby carnivores and omnivores pass the infectious stages in their faeces. Ingestion of this material may lead to successful infection of the ingesting animal. Although sarcocysts
Plasmodium
Plasmodium is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of Plasmodium species involve development in a blood-feeding insect host which injects parasites into a vertebrate host during a blood meal. Parasites grow within a vertebrate body tissue before entering the bloodstream to infect red blood cells; the ensuing destruction of host red blood cells can result in disease, called malaria. During this infection, some parasites are picked up by a blood-feeding insect, continuing the life cycle. Plasmodium is a member of the phylum Apicomplexa, a large group of parasitic eukaryotes. Within Apicomplexa, Plasmodium is in the order family Plasmodiidae. Over 200 species of Plasmodium have been described, many of which have been subdivided into 14 subgenera based on parasite morphology and host range. Evolutionary relationships among different Plasmodium species do not always follow taxonomic boundaries. Species of Plasmodium are distributed globally.
Insect hosts are most mosquitoes of the genera Culex and Anopheles. Vertebrate hosts include reptiles and mammals. Plasmodium parasites were first identified in the late 19th century by Charles Laveran. Over the course of the 20th century, many other species were discovered in various hosts and classified, including five species that infect humans: P. vivax, P. falciparum, P. malariae, P. ovale, P. knowlesi. P. falciparum is by far the most lethal in humans, resulting in hundreds of thousands of deaths per year. A number of drugs have been developed to treat Plasmodium infection; the genus Plasmodium consists of all eukaryotes in the phylum Apicomplexa that both undergo the asexual replication process of merogony inside host red blood cells and produce the crystalline pigment hemozoin as a byproduct of digesting host hemoglobin. Plasmodium species contain many features that are common to other eukaryotes, some that are unique to their phylum or genus; the Plasmodium genome is separated into 14 chromosomes contained in the nucleus.
Plasmodium parasites maintain a single copy of their genome through much of the life cycle, doubling the genome only for a brief sexual exchange within the midgut of the insect host. Attached to the nucleus is the endoplasmic reticulum, which functions to the ER in other eukaryotes. Proteins are trafficked from the ER to the Golgi apparatus which consists of a single membrane-bound compartment in Apicomplexans. From here proteins are trafficked to the cell surface. Like other apicomplexans, Plasmodium species have several cellular structures at the apical end of the parasite that serve as specialized organelles for secreting effectors into the host; the most prominent are the bulbous rhoptries which contain parasite proteins involved in invading the host cell and modifying the host once inside. Adjacent to the rhoptries are smaller structures termed micronemes that contain parasite proteins required for motility as well as recognizing and attaching to host cells. Spread throughout the parasite are secretory vesicles called dense granules that contain parasite proteins involved in modifying the membrane that separates the parasite from the host, termed the parasitophorous vacuole.
Species of Plasmodium contain two large membrane-bound organelles of endosymbiotic origin, the mitochondrion and the apicoplast, both of which play key roles in the parasite's metabolism. Unlike mammalian cells which contain many mitochondria, Plasmodium cells contain a single large mitochondrion that coordinates its division with that of the Plasmodium cell. Like in other eukaryotes, the Plasmodium mitochondrion is capable of generating energy in the form of ATP via the citric acid cycle. A second organelle, the apicoplast, is derived from a secondary endosymbiosis event, in this case the acquisition of a red algae by the Plasmodium ancestor; the apicoplast is involved in the synthesis of various metabolic precursors, including fatty acids, iron-sulphur clusters, components of the heme biosynthesis pathway. The life cycle of Plasmodium involves several distinct stages in the vertebrate hosts. Parasites are introduced into a vertebrate host by the bite of an insect host. Parasites first infect the liver or other tissue, where they undergo a single large round of replication before exiting the host cell to infect erythrocytes.
At this point, some species of Plasmodium of primates can form a long-lived dormant stage called a hypnozoite. It can remain in the liver for more than a year. However, for most Plasmodium species, the parasites in infected liver cells are only what are called merozoites. After emerging from the liver, they enter red blood cells, they go through continuous cycles of erythrocyte infection, while a small percentage of parasites differentiate into a sexual stage called a gametocyte, picked up by an insect host taking a blood meal. In some hosts, invasion of erythrocytes by Plasmodium species can result in disease, called malaria; this can sometimes be severe followed by death of the host. In other hosts, Plasmodium infection can be asymptomatic. Within the red blood cells, the merozoites grow first to a ring-shaped form and to a larger form called a trophozoite. Trophozoites mature to s
Hepatocyte
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 70-85% of the liver's mass; these cells are involved in: Protein synthesis Protein storage Transformation of carbohydrates Synthesis of cholesterol, bile salts and phospholipids Detoxification and excretion of exogenous and endogenous substances Initiation of formation and secretion of bile The typical hepatocyte is cubical with sides of 20-30 µm. The typical volume of a hepatocyte is 3.4 x 10−9 cm3. Smooth endoplasmic reticulum is abundant in hepatocytes, whereas most cells in the body have only small amounts. Hepatocytes display an eosinophilic cytoplasm, reflecting numerous mitochondria, basophilic stippling due to large amounts of rough endoplasmic reticulum and free ribosomes. Brown lipofuscin granules are observed together with irregular unstained areas of cytoplasm; the average life span of the hepatocyte is 5 months. Hepatocyte nuclei are round with prominent nucleoli. Anisokaryosis is common and reflects tetraploidy and other degrees of polyploidy, a normal feature of 30-40% of hepatocytes in the adult human liver.
Binucleate cells are common. Hepatocytes are organised into plates separated by vascular channels, an arrangement supported by a reticulin network; the hepatocyte plates are two cells thick in the chicken. Sinusoids display a fenestrated endothelial cell lining; the endothelial cells have no basement membrane and are separated from the hepatocytes by the space of Disse, which drains lymph into the portal tract lymphatics. Kupffer cells are scattered between endothelial cells. Stellate cells produce extracellular matrix and collagen; the hepatocyte is a cell in the body that manufactures serum albumin and the prothrombin group of clotting factors. It is the main site for the synthesis of lipoproteins, transferrin and glycoproteins. Hepatocytes manufacture their own structural proteins and intracellular enzymes. Synthesis of proteins is by the rough endoplasmic reticulum, both the rough and smooth endoplasmic reticulum are involved in secretion of the proteins formed; the endoplasmic reticulum is involved in conjugation of proteins to lipid and carbohydrate moieties synthesized by, or modified within, the hepatocytes.
The liver forms fatty acids from carbohydrates and synthesizes triglycerides from fatty acids and glycerol. Hepatocytes synthesize apoproteins with which they assemble and export lipoproteins; the liver is the main site in the body for gluconeogenesis, the formation of carbohydrates from precursors such as alanine and oxaloacetate. The liver metabolizes chylomicron remnants, it synthesizes cholesterol from acetate and further synthesizes bile salts. The liver is the sole site of bile salts formation. Hepatocytes have the ability to metabolize and inactivate exogenous compounds such as drugs, insecticides, endogenous compounds such as steroids; the drainage of the intestinal venous blood into the liver requires efficient detoxification of miscellaneous absorbed substances to maintain homeostasis and protect the body against ingested toxins. One of the detoxifying functions of hepatocytes is to modify ammonia into urea for excretion; the most abundant organelle in liver cells is the smooth endoplasmic reticulum.
Primary hepatocytes are used in cell biological and biopharmaceutical research. In vitro model systems based on hepatocytes have been of great help to better understand the role of hepatocytes in physiological processes of the liver. In addition, pharmaceutical industry has relied on the use of hepatocytes in suspension or culture to explore mechanisms of drug metabolism and predict in vivo drug metabolism. For these purposes, hepatocytes are isolated from animal or human whole liver or liver tissue by collagenase digestion, a two-step process. In the first step, the liver is placed in an isotonic solution, in which calcium is removed to disrupt cell-cell tight junctions by the use of a calcium chelating agent. Next, a solution containing collagenase is added to separate the hepatocytes from the liver stroma; this process creates a suspension of hepatocytes, which can be seeded in multi-well plates and cultured for many days or weeks. For optimal results, culture plates should first be coated with an extracellular matrix to promote hepatocyte attachment and maintenance of the hepatic phenotype.
In addition, overlay with an additional layer of extracellular matrix is performed to establish a sandwich culture of hepatocytes. The application of a sandwich configuration supports prolonged maintenance of hepatocytes in culture. Freshly-isolated hepatocytes that are not used can be cryopreserved and stored, they do not proliferate in culture. Hepatocytes are intensely sensitive to damage during the cycles of cryopreservation including freezing and thawing. After the addition of classical cryoprotectants there is still damage done while being cryopreserved. Recent cryopreservation and resuscitatio
Plasmodium falciparum
Plasmodium falciparum is a unicellular protozoan parasite of humans, the deadliest species of Plasmodium that cause malaria in humans. It is transmitted through the bite of a female Anopheles mosquito, it is responsible for 50% of all malaria cases. It causes the disease's most dangerous form called falciparum malaria, it is therefore regarded as the deadliest parasite in humans, causing 435,000 deaths in 2017. It is associated with the development of blood cancer and is classified as Group 2A carcinogen; the species originated from the malarial parasite Laverania found in gorillas, around 10,000 years ago. Alphonse Laveran was the first to identify the parasite in 1880, named it Oscillaria malariae. Ronald Ross discovered its transmission by mosquito in 1897. Giovanni Battista Grassi elucidated the complete transmission from a female anopheline mosquito to humans in 1898. In 1897, William H. Welch created the name Plasmodium falciparum, which ICZN formally adopted in 1954. P. falciparum assumes several different forms during its life cycle.
The human-infective stage are sporozoites from the salivary gland of a mosquito. The sporozoites multiply in the liver to become merozoites; these merozoites invade the erythrocytes to form trophozoites and gametocytes, during which the symptoms of malaria are produced. In the mosquito, the gametocytes undergo sexual reproduction to a zygote. Ookinete forms oocyts from; as of the latest World Malaria Report of the World Health Organization, there were 219 million cases of malaria worldwide in 2017, up from 216 million cases in 2016. This resulted in an estimated 435,000 deaths; every malarial death is caused by P. falciparum, 93% of death occurs in Africa. Children under five years of age are most affected. In Sub-Saharan Africa, over 75% of cases were due to P. falciparum, whereas in most other malarial countries, less virulent plasmodial species predominate. Falciparum malaria was familiar to the ancient Greeks, who gave the general name πυρετός pyretós "fever". Hippocrates gave several descriptions on tertian quartan fever.
It was prevalent throughout the ancient Roman civilizations. It was the Romans who named the disease "malaria"—mala for bad, aria for air, as they believed that the disease was spread by contaminated air, or miasma. A German physician, Johann Friedrich Meckel, must have been the first to see P. falciparum but not knowing what it was. In 1847 he reported the presence of black pigment granules from the blood and spleen of a patient who died of malaria; the French Army physician Charles Louis Alphonse Laveran, while working at Bône Hospital identified the parasite as a causative pathogen of malaria in 1880. He presented his discovery before the French Academy of Medicine in Paris, published it in The Lancet, in 1881, he gave the scientific name Oscillaria malariae. But his discovery was received with skepticism because by that time leading physicians such as Theodor Albrecht Edwin Klebs and Corrado Tommasi-Crudeli claimed that they had discovered a bacterium as the pathogen of malaria. Laveran's discovery was accepted only after five years when Camillo Golgi confirmed the parasite using better microscope and staining technique.
Laveran was awarded the Nobel Prize in Medicine in 1907 for his work. In 1900, the Italian zoologist Giovanni Battista Grassi categorized Plasmodium species based on the timing of fever in the patient; the British physician Patrick Manson formulated the mosquito-malaria theory in 1894. His colleague Ronald Ross, a British Army surgeon, travelled to India to test the theory. Ross discovered in 1897; the next year, he demonstrated that a malarial parasite of birds could be transmitted by mosquitoes from one bird to another. Around the same time, Grassi demonstrated that P. falciparum was transmitted in humans only by female anopheline mosquito. Ross and Grassi were nominated for the Nobel Prize in Physiology or Medicine in 1902. Under controversial circumstances, only Ronald Ross was selected for the award. There was a long debate on the taxonomy, it was only in 1954 the International Commission on Zoological Nomenclature approved the binominal Plasmodium falciparum. The valid genus Plasmodium was created by two Italian physicians Ettore Marchiafava and Angelo Celli in 1885.
The species name was introduced by an American physician William Henry Welch in 1897. It is derived from the Latin falx, meaning "sickle" and parum meaning "like or equal to another". P. falciparum is now accepted to have evolved from Laverania species present in gorilla in Western Africa. Genetic diversity indicates; the closest relative of P. falciparum is P. praefalciparum, a parasite of gorillas, as supported by mitochondrial and nuclear DNA sequences. These two species are related to the chimpanzee parasite P. reichenowi, thought to be the closest relative of P. falciparum. P. falciparum was once thought to originate from a parasite of birds. Levels of genetic polymorphism are low within the P. falciparum genome compared to that of closely
Karyogamy
Karyogamy is the final step in the process of fusing together two haploid eukaryotic cells, refers to the fusion of the two nuclei. Before karyogamy, each haploid cell has one complete copy of the organism's genome. In order for karyogamy to occur, the cell membrane and cytoplasm of each cell must fuse with the other in a process known as plasmogamy. Once within the joined cell membrane, the nuclei are referred to as pronuclei. Once the cell membranes and pronuclei fuse together, the resulting single cell is diploid, containing two copies of the genome; this diploid cell, called a zygote or zygospore can enter meiosis, or continue to divide by mitosis. Mammalian fertilization uses a comparable process to combine haploid sperm and egg cells to create a diploid fertilized egg; the term karyogamy comes from the Greek karyo- meaning "nut" and γάμος gamos, meaning "marriage". Haploid organisms such as fungi and algae can have complex cell cycles, in which the choice between sexual or asexual reproduction is fluid, influenced by the environment.
Some organisms, in addition to their usual haploid state, can exist as diploid for a short time, allowing genetic recombination to occur. Karyogamy can occur within either mode of reproduction: in somatic cells. Thus, karyogamy is the key step in bringing together two sets of different genetic material which can recombine during meiosis. In haploid organisms that lack sexual cycles, karyogamy can be an important source of genetic variation during the process of forming somatic diploid cells. Formation of somatic diploids circumvents the process of gamete formation during the sexual reproduction cycle and instead creates variation within the somatic cells of an developed organism, such as a fungus; the role of karyogamy in sexual reproduction can be demonstrated most by single-celled haploid organisms such as the algae of genus Chlamydomonas or the yeast Saccharomyces cerevisiae. Such organisms exist in a haploid state, containing only one set of chromosomes per cell. However, the mechanism remains the same among all haploid eukaryotes.
When subjected to environmental stress, such as nitrogen starvation in the case of Chlamydomonas, cells are induced to form gametes. Gamete formation in single-celled haploid organisms such as yeast is called sporulation, resulting in many cellular changes that increase resistance to stress. Gamete formation in multicellular fungi occurs in the gametangia, an organ specialized for such a process by meiosis; when opposite mating types meet, they are induced to leave the vegetative cycle and enter the mating cycle. In yeast, there are two mating types, a and α. In fungi, there can be two, four, or up to 10,000 mating types, depending on the species. Mate recognition in the simplest eukaryotes is achieved through pheromone signaling, which induces shmoo formation and begins the process of microtubule organization and migration. Pheromones used in mating type recognition are peptides, but sometimes trisporic acid or other molecules, recognized by cellular receptors on the opposite cell. Notably, pheromone signaling is absent in higher fungi such as mushrooms.
The cell membranes and cytoplasm of these haploid cells fuse together in a process known as plasmogamy. This results in a single cell with two nuclei, known as pronuclei; the pronuclei fuse together in a well regulated process known as karyogamy. This creates a diploid cell known as a zygote, or a zygospore, which can enter meiosis, a process of chromosome duplication and cell division, to create four new haploid gamete cells. One possible advantage of sexual reproduction is that it results in more genetic variability, providing the opportunity for adaptation through natural selection. Another advantage is efficient recombinational repair of DNA damages during meiosis. Thus, karyogamy is the key step in bringing together a variety of genetic material in order to ensure recombination in meiosis; the Amoebozoa is a large group of single-celled species that have been determined to have the machinery for karyogamy and meiosis. Since the Amoeboza branched off early from the eukaryotic family tree, this finding suggests that karyogamy and meiosis were present early in eukaryotic evolution.
The ultimate goal of karyogamy is fusion of the two haploid nuclei. The first step in this process is the movement of the two pronuclei toward each other, which occurs directly after plasmogamy; each pronucleus has a spindle pole body, embedded in the nuclear envelope and serves as an attachment point for microtubules. Microtubules, an important fiber-like component of the cytoskeleton, emerge at the spindle pole body; the attachment point to the spindle pole body marks the minus end, the plus end extends into the cytoplasm. The plus end has normal roles in mitotic division, but during nuclear congression, the plus ends are redirected; the microtubule plus ends attach to the opposite pronucleus, resulting in the pulling of the two pronuclei toward each other. Microtubule movement is mediated by a family of motor proteins known as kinesins, such as Kar3 in yeast. Accessory proteins, such as Spc72 in yeast, act as a glue, connecting the motor protein, spindle pole body and microtubule in a structure known as the half-bridge.
Other proteins, such as Kar9 and Bim1 in yeast, attach to the plus end of the microtubules. They are activated by pheromone signals to attach to the shmoo tip. A shmoo is a projection of the cellular membrane, the site of initial cell fusion in plasmogamy. After plasmogamy, the microtubule plus
