Affinity electrophoresis
Affinity electrophoresis is a general name for many analytical methods used in biochemistry and biotechnology. Both qualitative and quantitative information may be obtained through affinity electrophoresis; the methods include the so-called electrophoretic mobility shift assay, charge shift electrophoresis and affinity capillary electrophoresis. The methods are based on changes in the electrophoretic pattern of molecules through biospecific interaction or complex formation; the interaction or binding of a molecule, charged or uncharged, will change the electrophoretic properties of a molecule. Membrane proteins may be identified by a shift in mobility induced by a charged detergent. Nucleic acids or nucleic acid fragments may be characterized by their affinity to other molecules; the methods have been used for estimation of binding constants, as for instance in lectin affinity electrophoresis or characterization of molecules with specific features like glycan content or ligand binding. For enzymes and other ligand-binding proteins, one-dimensional electrophoresis similar to counter electrophoresis or to "rocket immunoelectrophoresis", affinity electrophoresis may be used as an alternative quantification of the protein.
Some of the methods are similar to affinity chromatography by use of immobilized ligands. There is ongoing research in developing new ways of utilizing the knowledge associated with affinity electrophoresis to improve its functionality and speed, as well as attempts to improve established methods and tailor them towards performing specific tasks. A type of electrophoretic mobility shift assay, agarose gel electrophoresis is used to separate protein-bound amino acid complexes from free amino acids. Using a low voltage to minimize the risk for heat damage, electricity is run across an agarose gel; this technique utilizes a high voltage with a 0.5× Tris-borate buffer run across an agarose gel. This method differs from the traditional agarose gel electrophoresis by utilizing a higher voltage to facilitate a shorter run time as well as yield a higher band resolution. Other factors included in developing the technique of rapid agarose gel electrophoresis are gel thickness, the percentage of agarose within the gel.
Boronate affinity electrophoresis utilizes boronic acid infused acrylimide gels to purify NAD-RNA. This purification allows for researchers to measure the kinetic activity of NAD-RNA decapping enzymes. Affinity capillary electrophoresis utilizes a formulary approach in accordance with the theory of electromigration; this method utilizes the inter-molecular interactions found in a free solution. "Affinity probes" consisting of fluorophore-labeled molecules that will bind to target molecules are mixed with the sample being tested. This mixture and its subsequent complexes are separated through capillary electrophoresis; the principle behind this type of electrophoresis is the mobility of the target molecules being altered by inter-molecular interactions. Affinity-trap polyacrylamide gel electrophoresis has become one of the most popular methods of protein separation; this is not only due to its separation qualities, but because it can be used in conjunction with a variety of other analytic methods, such as mass spectrometry, western blotting.
This method utilizes a two-step approach. First, a protein sample is run through a polyacrylamide gel using electrophoresis; the sample is transferred to a different polyacrylamide gel where affinity probes are immobilized. The proteins that do not have affinity for the affinity probes pass through the affinity-trap gel, proteins with affinity for the probes will be "trapped" by the immobile affinity probes; these trapped proteins are visualized and identified using mass spectrometry after in-gel digestion. Phosphate affinity electrophoresis utilizes an affinity probe which consists of a molecule that binds to divalent phosphate ions in neutral aqueous solution, known as a "Phos-Tag"; this methods utilizes a separation gel made of an acrylamide-pendent Phos-Tag monomer, copolymerized. Phosphorylated proteins migrate in the gel compared to non-phosphorylated proteins; this technique gives the researcher the ability to observe the differences in the phosphorylation states of any given protein. Immunoelectrophoresis Comprehensive texts edited by Niels H. Axelsen in Scandinavian Journal of Immunology, 1975 Volume 4 Supplement
Gene
In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA; the RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait; these genes make up different DNA sequences called genotypes. Genotypes along with developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions; some genetic traits are visible, such as eye color or number of limbs, some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life. Genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population; these alleles encode different versions of a protein, which cause different phenotypical traits.
Usage of the term "having a gene" refers to containing a different allele of the same, shared gene. Genes evolve due to natural selection / survival of the fittest and genetic drift of the alleles; the concept of a gene continues to be refined. For example, regulatory regions of a gene can be far removed from its coding regions, coding regions can be split into several exons; some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. Therefore, a broad, modern working definition of a gene is any discrete locus of heritable, genomic sequence which affect an organism's traits by being expressed as a functional product or by regulation of gene expression; the term gene was introduced by Danish botanist, plant physiologist and geneticist Wilhelm Johannsen in 1909. It is inspired by the ancient Greek: γόνος, that means offspring and procreation; the existence of discrete inheritable units was first suggested by Gregor Mendel. From 1857 to 1864, in Brno, he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring.
He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas. Although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics; this description prefigured Wilhelm Johannsen's distinction between phenotype. Mendel was the first to demonstrate independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, the phenomenon of discontinuous inheritance. Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance, which suggested that each parent contributed fluids to the fertilisation process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan and genesis / genos. Darwin used the term gemmule to describe hypothetical particles. Mendel's work went unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries, Carl Correns, Erich von Tschermak, who reached similar conclusions in their own research.
In 1889, Hugo de Vries published his book Intracellular Pangenesis, in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes", after Darwin's 1868 pangenesis theory. Sixteen years in 1905, Wilhelm Johannsen introduced the term'gene' and William Bateson that of'genetics' while Eduard Strasburger, amongst others, still used the term'pangene' for the fundamental physical and functional unit of heredity. Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s; the structure of DNA was studied by Rosalind Franklin and Maurice Wilkins using X-ray crystallography, which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication.
In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination and arranged like beads on a string. The experiments of Benzer using mutants defective in the rII region of bacteriophage T4 showed that individual genes have a simple linear structure and are to be equivalent to a linear section of DNA. Collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, transcribed from DNA; this dogma has since been shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics. In 1972, Walter Fiers and his team were the first to determine the sequence of a gene: that of Bacteriophage MS2 coat protein; the subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool.
An automated version of the Sanger method was used in early phases of the
Alternative splicing
Alternative splicing, or differential splicing, is a regulated process during gene expression that results in a single gene coding for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA produced from that gene; the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and in their biological functions. Notably, alternative splicing allows the human genome to direct the synthesis of many more proteins than would be expected from its 20,000 protein-coding genes. Alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the biodiversity of proteins that can be encoded by the genome. There are numerous modes of alternative splicing observed, of which the most common is exon skipping. In this mode, a particular exon may be included in mRNAs under some conditions or in particular tissues, omitted from the mRNA in others; the production of alternatively spliced mRNAs is regulated by a system of trans-acting proteins that bind to cis-acting sites on the primary transcript itself.
Such proteins include splicing activators that promote the usage of a particular splice site, splicing repressors that reduce the usage of a particular site. Mechanisms of alternative splicing are variable, new examples are being found through the use of high-throughput techniques. Researchers hope to elucidate the regulatory systems involved in splicing, so that alternative splicing products from a given gene under particular conditions could be predicted by a "splicing code". Abnormal variations in splicing are implicated in disease. Abnormal splicing variants are thought to contribute to the development of cancer, splicing factor genes are mutated in different types of cancer. Alternative splicing was first observed in 1977; the Adenovirus produces five primary transcripts early in its infectious cycle, prior to viral DNA replication, an additional one after DNA replication begins. The early primary transcripts continue to be produced; the additional primary transcript produced late in infection is large and comes from 5/6 of the 32kb adenovirus genome.
This is much larger. Researchers found that the primary RNA transcript produced by adenovirus type 2 in the late phase was spliced in many different ways, resulting in mRNAs encoding different viral proteins. In addition, the primary transcript contained multiple polyadenylation sites, giving different 3’ ends for the processed mRNAs. In 1981, the first example of alternative splicing in a transcript from a normal, endogenous gene was characterized; the gene encoding the thyroid hormone calcitonin was found to be alternatively spliced in mammalian cells. The primary transcript from this gene contains 6 exons. Another mRNA is produced from this pre-mRNA by skipping exon 4, includes exons 1–3, 5, 6, it encodes a protein known as CGRP. Examples of alternative splicing in immunoglobin gene transcripts in mammals were observed in the early 1980s. Since alternative splicing has been found to be ubiquitous in eukaryotes; the "record-holder" for alternative splicing is a D. melanogaster gene called Dscam, which could have 38,016 splice variants.
Five basic modes of alternative splicing are recognized. Exon skipping or cassette exon: in this case, an exon may be spliced out of the primary transcript or retained; this is the most common mode in mammalian pre-mRNAs. Mutually exclusive exons: One of two exons is retained in mRNAs after splicing, but not both. Alternative donor site: An alternative 5' splice junction is used, changing the 3' boundary of the upstream exon. Alternative acceptor site: An alternative 3' splice junction is used, changing the 5' boundary of the downstream exon. Intron retention: A sequence may be spliced out as an intron or retained; this is distinguished from exon skipping. If the retained intron is in the coding region, the intron must encode amino acids in frame with the neighboring exons, or a stop codon or a shift in the reading frame will cause the protein to be non-functional; this is the rarest mode in mammals. In addition to these primary modes of alternative splicing, there are two other main mechanisms by which different mRNAs may be generated from the same gene.
Use of multiple promoters is properly described as a transcriptional regulation mechanism rather than alternative splicing. At the other end, multiple polyadenylation sites provide different 3' end points for the transcript. Both of these mechanisms are found in combination with alternative splicing and provide additional variety in mRNAs derived from a gene; these modes describe basic splicing mechanisms, but may be inadequate to describe complex splicing events. For instance, the figure to the right shows 3 spliceforms from the mouse hyaluronidase 3 gene. Comparing the exonic structure shown in the first line with the one in the second line shows intron retention, whereas the comparison between the second and the third spliceform exhibits exon skipping. A model nomenclature to un
Oligosaccharide
An oligosaccharide is a saccharide polymer containing a small number of monosaccharides. Oligosaccharides can have many functions including cell binding. For example, glycolipids have an important role in the immune response, they are present as glycans: oligosaccharide chains linked to lipids or to compatible amino acid side chains in proteins, by N- or O-glygosidic bonds. N-linked oligosaccharides are always pentasaccharides attached to asparagine via a beta linkage to the amine nitrogen of the side chain. Alternately, O-linked oligosaccharides are attached to threonine or serine on the alcohol group of the side chain. Not all natural oligosaccharides occur as components of glycolipids. Some, such as the raffinose series, occur as transport carbohydrates in plants. Others, such as maltodextrins or cellodextrins, result from the microbial breakdown of larger polysaccharides such as starch or cellulose. In biology, glycosylation is the process by which a carbohydrate is covalently attached to an organic molecule, creating structures such as glycoproteins and glycolipids.
N-linked glycosylation involves oligosaccharide attachment to asparagine via a beta linkage to the amine nitrogen of the side chain. The process of N-linked glycosylation occurs cotranslationally, or concurrently while the proteins is being translated. Since it is added cotranslationally, it is believed that N-linked glycosylation helps determine the folding of polypeptides due to the hydrophilic nature of sugars. All N-linked Oligosaccharides are pentasaccharides: five monosaccharides long. In N-glycosylation for eukaryotes, the oligosaccharide substrate is assembled right at the membrane of the endoplasmatic reticulum. For prokaryotes, this process occurs at the plasma membrane. In both cases, the acceptor substrate is an asparagine residue; the asparagine residue linked to an N-linked oligosaccharide occurs in the sequence Asn-X-Ser/Thr, where X can be any amino acid except for proline, although it is rare to see Asp, Leu, or Trp in this position. Oligosaccharides that participate in O-linked glycosylation are attached to threonine or serine on the hydroxyl group of the side chain.
O-linked glycosylation occurs in the golgi apparatus, where monosaccharide units are added to a complete polypeptide chain. Cell surface proteins and extracellular proteins are O-glycosylated. Glycosylation sites in O-linked oligosaccharides are determined by the secondary and tertiary structures of the polypeptide, which dictate where glycosyltransferases will add sugars. Glycoproteins and glycolipids are by definition covalently bonded to carbohydrates, they are abundant on the surface of the cell, their interactions contribute to the overall stability of the cell. Glycoproteins have distinct Oligosaccharide structures which have significant effects on many of their properties, affecting critical functions such as antigenicity and resistance to proteases. Glycoproteins are relevant as cell-surface receptors, cell-adhesion molecules and tumor antigens. Glycolipids are important for cell recognition, are important for modulating the function of membrane proteins that act as receptors. Glycolipids are lipid molecules bound to oligosaccharides present in the lipid bilayer.
Additionally, they can serve as receptors for cellular cell signaling. The head of the oligosaccharide serves as a binding partner in receptor activity; the binding mechanisms of receptors to the oligosaccharides depends on the composition of the oligosaccharides that are exposed or presented above the surface of the membrane. There is great diversity in the binding mechanisms of glycolipids, what makes them such an important target for pathogens as a site for interaction and entrance. For example, the chaperone activity of glycolipids has been studied for its relevance to HIV infection. All cells are coated in either glycoproteins or glycolipids, both of which help determine cell types. Lectins, or proteins that bind carbohydrates, can recognize specific oligosaccharides and provide useful information for cell recognition based on oligosaccharide binding. An important example of oligosaccharide cell recognition is the role of glycolipids in determining blood types; the various blood types are distinguished by the glycan modification present on the surface of blood cells.
These can be visualized using mass spectrometry. The oligosaccharides found on the A, B, H antigen occur on the non-reducing ends of the oligosaccharide; the H antigen serves as a precursor for the B antigen. Therefore, a person with A blood type will have the A antigen and H antigen present on the glycolipids of the red blood cell plasma membrane. A person with B blood type will have the B and H antigen present. A person with AB blood type will have A, B, H antigens present, and a person with O blood type will only have the H antigen present. This means all blood types have the H antigen, which explains why the O blood type is known as the "universal donor". Many cells produce specific carbohydrate-binding proteins known as lectins, which mediate cell adhesion with oligosaccharides. Selectins - a family of lectins - mediate certain cell-cell adhesion processes, including those of leukocytes to endothelial cells. In an immune response, endothelial cells can express certain selectins transiently in response to damage or injury to the cells.
In response, a reciprocal selectin-oligosaccharide interaction will occur between the two molecules which allows the white blood cell to help eliminate the infection or damage. Protein-Carbohydrate bonding is mediated by
Glycosyltransferase
Glycosyltransferases are enzymes that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar to a nucleophilic glycosyl acceptor molecule, the nucleophile of which can be oxygen- carbon-, nitrogen-, or sulfur-based; the result of glycosyl transfer can be a carbohydrate, oligosaccharide, or a polysaccharide. Some glycosyltransferases catalyse transfer to inorganic water. Glycosyl transfer can occur to protein residues to tyrosine, serine, or threonine to give O-linked glycoproteins, or to asparagine to give N-linked glycoproteins. Mannosyl groups may be transferred to tryptophan to generate C-mannosyl tryptophan, abundant in eukaryotes. Transferases may use lipids as an acceptor, forming glycolipids, use lipid-linked sugar phosphate donors, such as dolichol phosphates. Glycosyltransferases that use sugar nucleotide donors are Leloir enzymes, after Luis F. Leloir, the scientist who discovered the first sugar nucleotide and who received the 1970 Nobel Prize in Chemistry for his work on carbohydrate metabolism.
Glycosyltransferases that use non-nucleotide donors such as dolichol or polyprenol pyrophosphate are non-Leloir glycosyltransferases. Mammals use only 9 sugar nucleotide donors for glycosyltransferases: UDP-glucose, UDP-galactose, UDP-GlcNAc, UDP-GalNAc, UDP-xylose, UDP-glucuronic acid, GDP-mannose, GDP-fucose, CMP-sialic acid; the phosphate of these donor molecules are coordinated by divalent cations such as manganese, however metal independent enzymes exist. Many glycosyltransferases are single-pass transmembrane proteins, they are anchored to membranes of Golgi apparatus Glycosyltransferases can be segregated into "retaining" or "inverting" enzymes according to whether the stereochemistry of the donor's anomeric bond is retained or inverted during the transfer; the inverting mechanism is straightforward, requiring a single nucleophilic attack from the accepting atom to invert stereochemistry. The retaining mechanism has been a matter of debate, but there exists strong evidence against a double displacement mechanism or a dissociative mechanism.
An "orthogonal associative" mechanism has been proposed which, akin to the inverting enzymes, requires only a single nucleophilic attack from an acceptor from a non-linear angle to achieve anomer retention. The recent discovery of the reversibility of many reactions catalyzed by inverting glycosyltransferases served as a paradigm shift in the field and raises questions regarding the designation of sugar nucleotides as'activated' donors. Sequence-based classification methods have proven to be a powerful way of generating hypotheses for protein function based on sequence alignment to related proteins; the carbohydrate-active enzyme database presents a sequence-based classification of glycosyltransferases into over 90 families. The same three-dimensional fold is expected to occur within each of the families. In contrast to the diversity of 3D structures observed for glycoside hydrolases, glycosyltransferase have a much smaller range of structures. In fact, according to the Structural Classification of Proteins database, only three different folds have been observed for glycosyltransferases Very a new glycosyltransferase fold was identified for the glycosyltransferases involved in the biosynthesis of the NAG-NAM polymer backbone of peptidoglycan.
Many inhibitors of glycosyltransferases are known. Some of these are natural products, such as moenomycin, an inhibitor of peptidoglycan glycosyltransferases, the nikkomycins, inhibitors of chitin synthase, the echinocandins, inhibitors of fungal b-1,3-glucan synthases; some glycosyltransferase inhibitors are of use as antibiotics. Moenomycin is used in animal feed as a growth promoter. Caspofungin is in use as an antifungal agent. Ethambutol is an inhibitor of mycobacterial arabinotransferases and is used for the treatment of tuberculosis. Lufenuron is used to control fleas in animals; the ABO blood group system is determined by what type of glycosyltransferases are expressed in the body. The ABO gene locus expressing the glycosyltransferases has three main allelic forms: A, B, O; the A allele encodes 1-3-N-acetylgalactosaminyltransferase that bonds α-N-acetylgalactosamine to D-galactose end of H antigen, producing the A antigen. The B allele encodes 1-3-galactosyltransferase that joins α-D-galactose bonded to D-galactose end of H antigen, creating the B antigen.
In case of O allele the exon 6 contains a deletion. The O allele differs from the A allele by deletion of a single nucleotide - Guanine at position 261; the deletion causes a frameshift and results in translation of an entirely different protein that lacks enzymatic activity. This results in H antigen remaining unchanged in case of O groups; the combination of glycosyltransferases by both alleles present in each person determines whether there is an AB, A, B or O blood type. Glycosyltransferases have been used in the both targeted synthesis of specific glycoconjugates as well as the synthesis of differentially glycosylated libraries of drugs, biological probes or natural products in the context of drug discovery and drug development. Suitable enzymes can be produced recombinantly; as an alternative, whole cell-based systems using either endogenous glycosyl donors o
Human Genome Project
The Human Genome Project was an international scientific research project with the goal of determining the sequence of nucleotide base pairs that make up human DNA, of identifying and mapping all of the genes of the human genome from both a physical and a functional standpoint. It remains the world's largest collaborative biological project. After the idea was picked up in 1984 by the US government when the planning started, the project formally launched in 1990 and was declared complete on April 14, 2003. Funding came from the US government through the National Institutes of Health as well as numerous other groups from around the world. A parallel project was conducted outside government by the Celera Corporation, or Celera Genomics, formally launched in 1998. Most of the government-sponsored sequencing was performed in twenty universities and research centers in the United States, the United Kingdom, France and China; the Human Genome Project aimed to map the nucleotides contained in a human haploid reference genome.
The "genome" of any given individual is unique. Therefore, the finished human genome is a mosaic; the Human Genome Project was a 15-year-long, publicly funded project initiated in 1990 with the objective of determining the DNA sequence of the entire euchromatic human genome within 15 years. In May 1985, Robert Sinsheimer organized a workshop to discuss sequencing the human genome, but for a number of reasons the NIH was uninterested in pursuing the proposal; the following March, the Santa Fe Workshop was organized by Charles DeLisi and David Smith of the Department of Energy's Office of Health and Environmental Research. At the same time Renato Dulbecco proposed whole genome sequencing in an essay in Science. James Watson followed two months with a workshop held at the Cold Spring Harbor Laboratory; the fact that the Santa Fe workshop was motivated and supported by a Federal Agency opened a path, albeit a difficult and tortuous one, for converting the idea into a public policy in the United States.
In a memo to the Assistant Secretary for Energy Research, Charles DeLisi, Director of the OHER, outlined a broad plan for the project. This started a long and complex chain of events which led to approved reprogramming of funds that enabled the OHER to launch the Project in 1986, to recommend the first line item for the HGP, in President Reagan's 1988 budget submission, approved by the Congress. Of particular importance in Congressional approval was the advocacy of Senator Peter Domenici, whom DeLisi had befriended. Domenici chaired the Senate Committee on Energy and Natural Resources, as well as the Budget Committee, both of which were key in the DOE budget process. Congress added a comparable amount to the NIH budget, thereby beginning official funding by both agencies. Alvin Trivelpiece sought and obtained the approval of DeLisi's proposal by Deputy Secretary William Flynn Martin; this chart was used in the spring of 1986 by Trivelpiece Director of the Office of Energy Research in the Department of Energy, to brief Martin and Under Secretary Joseph Salgado regarding his intention to reprogram $4 million to initiate the project with the approval of Secretary Herrington.
This reprogramming was followed by a line item budget of $16 million in the Reagan Administration’s 1987 budget submission to Congress. It subsequently passed both Houses; the Project was planned for 15 years. Candidate technologies were being considered for the proposed undertaking at least as early as 1985. In 1990, the two major funding agencies, DOE and NIH, developed a memorandum of understanding in order to coordinate plans and set the clock for the initiation of the Project to 1990. At that time, David Galas was Director of the renamed “Office of Biological and Environmental Research” in the U. S. Department of Energy's Office of Science and James Watson headed the NIH Genome Program. In 1993, Aristides Patrinos succeeded Galas and Francis Collins succeeded James Watson, assuming the role of overall Project Head as Director of the U. S. National Institutes of Health National Center for Human Genome Research. A working draft of the genome was announced in 2000 and the papers describing it were published in February 2001.
A more complete draft was published in 2003, genome "finishing" work continued for more than a decade. The $3-billion project was formally founded in 1990 by the US Department of Energy and the National Institutes of Health, was expected to take 15 years. In addition to the United States, the international consortium comprised geneticists in the United Kingdom, Australia and myriad other spontaneous relationships. Considering the inflation, the project costed $5 billion. Due to widespread international cooperation and advances in the field of genomics, as well as major advances in computing technology, a'rough draft' of the genome was finished in 2000; this first available rough draft assembly of the genome was completed by the Genome Bioinformatics Group at the University of California, Santa Cruz led by graduate student Jim Kent. Ongoing sequencing led to the announcement of the complete genome on April 14, 2003, two years earlier than planned. In May 2006, another milestone was passed on the way to completion of the project, when the sequence of
Polymorphism (biology)
Polymorphism in biology and zoology is the occurrence of two or more different morphs or forms referred to as alternative phenotypes, in the population of a species. To be classified as such, morphs must occupy the same habitat at the same time and belong to a panmictic population; the term polyphenism can be used to clarify. Genetic polymorphism is a term used somewhat differently by geneticists and molecular biologists to describe certain mutations in the genotype, such as single nucleotide polymorphisms that may not always correspond to a phenotype, but always corresponds to a branch in the genetic tree. See below. Polymorphism is common in nature. Polymorphism functions to retain variety of form in a population living in a varied environment; the most common example is sexual dimorphism. Other examples are mimetic forms of butterflies, human hemoglobin and blood types. According to the theory of evolution, polymorphism results from evolutionary processes, as does any aspect of a species, it is modified by natural selection.
In polyphenism, an individual's genetic makeup allows for different morphs, the switch mechanism that determines which morph is shown is environmental. In genetic polymorphism, the genetic makeup determines the morph; the term polymorphism refers to the occurrence of structurally and functionally more than two different types of individuals, called zooids, within the same organism. It is a characteristic feature of cnidarians. For example, Obelia has the gastrozooids. Although in general use, polymorphism is a broad term. In biology, polymorphism has been given a specific meaning. A more specific term, when only two forms occur, is dimorphism; the term omits characteristics showing continuous variation. Polymorphism deals with forms in which the variation is discrete or bimodal or polymodal. Morphs must occupy the same habitat at the same time; the use of the words "morph" or "polymorphism" for what is a visibly different geographical race or variant is common, but incorrect. The significance of geographical variation is in that it may lead to allopatric speciation, whereas true polymorphism takes place in panmictic populations.
The term was first used to describe visible forms, but nowadays it has been extended to include cryptic morphs, for instance blood types, which can be revealed by a test. Rare variations are not classified as polymorphisms, mutations by themselves do not constitute polymorphisms. To qualify as a polymorphism, some kind of balance must exist between morphs underpinned by inheritance; the criterion is that the frequency of the least common morph is too high to be the result of new mutations or, as a rough guide, that it is greater than 1%. Polymorphism crosses several discipline boundaries, including ecology and genetics, evolution theory, taxonomy and biochemistry. Different disciplines may give the same concept different names, different concepts may be given the same name. For example, there are the terms established in ecological genetics by E. B. Ford, for classical genetics by John Maynard Smith; the shorter term morphism may be more accurate than polymorphism, but is not used. It was the preferred term of the evolutionary biologist Julian Huxley.
Various synonymous terms exist for the various polymorphic forms of an organism. The most common are morpha, while a more formal term is morphotype. Form and phase are sometimes used, but are confused in zoology with "form" in a population of animals, "phase" as a color or other change in an organism due to environmental conditions. Phenotypic traits and characteristics are possible descriptions, though that would imply just a limited aspect of the body. In the taxonomic nomenclature of zoology, the word "morpha" plus a Latin name for the morph can be added to a binomial or trinomial name. However, this invites confusion with geographically variant ring species or subspecies if polytypic. Morphs have no formal standing in the ICZN. In botanical taxonomy, the concept of morphs is represented with the terms "variety", "subvariety" and "form", which are formally regulated by the ICN. Horticulturists sometimes confuse this usage of "variety" both with cultivar and with the legal concept "plant variety".
Three mechanisms may cause polymorphism: Genetic polymorphism – where the phenotype of each individual is genetically determined A conditional development strategy, where the phenotype of each individual is set by environmental cues A mixed development strategy, where the phenotype is randomly assigned during development Selection, whether natural or artificial, changes the frequency of morphs within a population. A genetic polymorphism persists over many generations, maintained by two or more opposed and powerful selection pressures. Diver found banding morphs in Cepaea nemoralis could be seen in prefossil shells going back to t
