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
Hepatitis B virus
Hepatitis B virus, abbreviated HBV, is a double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B. In addition to causing hepatitis, infection with HBV can lead to cirrhosis and hepatocellular carcinoma, it has been suggested that it may increase the risk of pancreatic cancer. Viral infection by Hepatitis B virus causes many hepatocyte changes due to the direct action of a protein encoded by the virus, HBx, to indirect changes due to a large increase in intracellular reactive oxygen species after infection. HBx appears to dysregulate a number of cellular pathways. HBx causes dysregulation in part by binding to genomic DNA, changing expression patterns of miRNAs, affecting histone methyltransferases, binding to SIRT1 protein to activate transcription, cooperating with histone methylases and demethylases to change cell expression patterns. HBx is responsible for the approximate 10,000-fold increase in intracellular ROS upon chronic HBV infection.
Increased ROS can be caused, in part, by localization of HBx to the mitochondria where HBx decreases the mitochondrial membrane potential. In addition, another HBV protein, HBsAg increases ROS through interactions with the endoplasmic reticulum; the increase in reactive oxygen species after HBV infection causes inflammation, which leads to a further increase in ROS. ROS cause more than 20 types of DNA damage. Oxidative DNA damage is mutagenic. In addition, repair of the DNA damage can cause epigenetic alterations at the site of the damage during repair of the DNA. Epigenetic alterations and mutations may cause defects in the cellular machinery that contribute to liver disease. By the time accumulating epigenetic and mutational changes cause progression to cancer, epigenetic alterations appear to have a larger role in this carcinogenesis than mutations. Only one or two genes, TP53 and ARID1A, are mutated in more than 20% of liver cancers while 41 genes each have hypermethylated promoters in more than 20% of liver cancers, with seven of these genes being hypermethylated in more than 75% of liver cancers.
In addition to alterations at the sites of DNA repair, epigenetic alterations are caused by HBx recruiting the DNA methyltransferase enzymes, DNMT1 and/or DNMT3A, to specific gene loci to alter their methylation levels and gene expression. HBx alters histone acetylation that can affect gene expression. Several thousand protein-coding genes appear to have HBx-binding sites. In addition to protein coding genes, about 15 microRNAs and 16 Long non-coding RNAs are affected by the binding of HBx to their promoters; each altered microRNA can affect the expression of several hundred messenger RNAs. Hepatitis B virus is classified as the type species of the Orthohepadnavirus, which contains eight other species; the genus is classified as part of the Hepadnaviridae family, which contains one other genus, Avihepadnavirus. This family of viruses have not been assigned to a viral order. Viruses similar to hepatitis B have been found in all apes, in Old World monkeys, in a New World woolly monkeys suggesting an ancient origin for this virus in primates.
The virus is divided into four major serotypes based on antigenic epitopes present on its envelope proteins. These serotypes are based on two mutually exclusive determinant pairs; the viral strains have been divided into ten genotypes and forty subgenotypes according to overall nucleotide sequence variation of the genome. The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus. Differences between genotypes affect the disease severity and likelihood of complications, response to treatment and vaccination; the serotypes and genotypes do not correspond. Genotype D has 10 subgenotypes. A number of as yet unclassified Hepatitis B like species have been isolated from bats. Hepatitis B virus is a member of the Hepadnavirus family; the virus particle, called Dane particle, consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity similar to retroviruses.
The outer envelope contains embedded proteins which are involved in viral binding of, entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses with a virion diameter of 42 nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core; these particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, called the surface antigen, is produced in excess during the life cycle of the virus. It consists of: HBsAg HBcAg Hepatitis B virus DNA polymerase HBx; the function of this protein is not yet well known, but evidence suggests it plays a part in the activation of the viral transcription process. Hepatitis D virus requires HBV envelope particles to become virulent; the early evolution of the Hepatitis B, like that of all viruses, is difficult to establish. The divergence of orthohepadnavirus and avihepadnavirus occurred ~125,000 years ago. Both the Avihepadnavirus and Orthohepadna viruses began to diversify about 25,000 years ago.
The branching at this time lead to the emergence of the Orthohepadna genotypes A–H. Human strains have a most recent common ancestor dating back to 7,000 to 10,000 years ago; the Av
A chromosome is a deoxyribonucleic acid molecule with part or all of the genetic material of an organism. Most eukaryotic chromosomes include packaging proteins which, aided by chaperone proteins, bind to and condense the DNA molecule to prevent it from becoming an unmanageable tangle. Chromosomes are visible under a light microscope only when the cell is undergoing the metaphase of cell division. Before this happens, every chromosome is copied once, the copy is joined to the original by a centromere, resulting either in an X-shaped structure if the centromere is located in the middle of the chromosome or a two-arm structure if the centromere is located near one of the ends; the original chromosome and the copy are now called sister chromatids. During metaphase the X-shape structure is called a metaphase chromosome. In this condensed form chromosomes are easiest to distinguish and study. In animal cells, chromosomes reach their highest compaction level in anaphase during chromosome segregation.
Chromosomal recombination during meiosis and subsequent sexual reproduction play a significant role in genetic diversity. If these structures are manipulated incorrectly, through processes known as chromosomal instability and translocation, the cell may undergo mitotic catastrophe; this will make the cell initiate apoptosis leading to its own death, but sometimes mutations in the cell hamper this process and thus cause progression of cancer. Some use the term chromosome in a wider sense, to refer to the individualized portions of chromatin in cells, either visible or not under light microscopy. Others use the concept in a narrower sense, to refer to the individualized portions of chromatin during cell division, visible under light microscopy due to high condensation; the word chromosome comes from the Greek χρῶμα and σῶμα, describing their strong staining by particular dyes. The term was coined by von Waldeyer-Hartz, referring to the term chromatin, introduced by Walther Flemming; some of the early karyological terms have become outdated.
For example and Chromosom, both ascribe color to a non-colored state. The German scientists Schleiden, Virchow and Bütschli were among the first scientists who recognized the structures now familiar as chromosomes. In a series of experiments beginning in the mid-1880s, Theodor Boveri gave the definitive demonstration that chromosomes are the vectors of heredity, it is the second of these principles, so original. Wilhelm Roux suggested. Boveri was able to confirm this hypothesis. Aided by the rediscovery at the start of the 1900s of Gregor Mendel's earlier work, Boveri was able to point out the connection between the rules of inheritance and the behaviour of the chromosomes. Boveri influenced two generations of American cytologists: Edmund Beecher Wilson, Nettie Stevens, Walter Sutton and Theophilus Painter were all influenced by Boveri. In his famous textbook The Cell in Development and Heredity, Wilson linked together the independent work of Boveri and Sutton by naming the chromosome theory of inheritance the Boveri–Sutton chromosome theory.
Ernst Mayr remarks that the theory was hotly contested by some famous geneticists: William Bateson, Wilhelm Johannsen, Richard Goldschmidt and T. H. Morgan, all of a rather dogmatic turn of mind. Complete proof came from chromosome maps in Morgan's own lab; the number of human chromosomes was published in 1923 by Theophilus Painter. By inspection through the microscope, he counted 24 pairs, his error was copied by others and it was not until 1956 that the true number, 46, was determined by Indonesia-born cytogeneticist Joe Hin Tjio. The prokaryotes – bacteria and archaea – have a single circular chromosome, but many variations exist; the chromosomes of most bacteria, which some authors prefer to call genophores, can range in size from only 130,000 base pairs in the endosymbiotic bacteria Candidatus Hodgkinia cicadicola and Candidatus Tremblaya princeps, to more than 14,000,000 base pairs in the soil-dwelling bacterium Sorangium cellulosum. Spirochaetes of the genus Borrelia are a notable exception to this arrangement, with bacteria such as Borrelia burgdorferi, the cause of Lyme disease, containing a single linear chromosome.
Prokaryotic chromosomes have less sequence-based structure than eukaryotes. Bacteria have a one-point from which replication starts, whereas some archaea contain multiple replication origins; the genes in prokaryotes are organized in operons, do not contain introns, unlike eukaryotes. Prokaryotes do not possess nuclei. Instead, their DNA is organized into a structure called the nucleoid; the nucleoid occupies a defined region of the bacterial cell. This structure is, dynamic and is maintained and remodeled by the actions of a range of histone-like proteins, which associate with the bacterial chromosome. In archaea, the DNA in chromosomes is more organized, with the DNA packaged within structures similar to eukaryotic nucleosomes. Certain bacteria contain plasmids or other extrachromosomal DNA; these are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer. In prokaryotes and viruses, the DNA is densely packed and organized.
Heredity is the passing on of traits from parents to their offspring, either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic information of their parents. Through heredity, variations between individuals can accumulate and cause species to evolve by natural selection; the study of heredity in biology is genetics. In humans, eye color is an example of an inherited characteristic: an individual might inherit the "brown-eye trait" from one of the parents. Inherited traits are controlled by genes and the complete set of genes within an organism's genome is called its genotype; the complete set of observable traits of the structure and behavior of an organism is called its phenotype. These traits arise from the interaction of its genotype with the environment; as a result, many aspects of an organism's phenotype are not inherited. For example, suntanned skin comes from the interaction between a person's sunlight. However, some people tan more than others, due to differences in their genotype: a striking example is people with the inherited trait of albinism, who do not tan at all and are sensitive to sunburn.
Heritable traits are known to be passed from one generation to the next via DNA, a molecule that encodes genetic information. DNA is a long polymer; the sequence of bases along a particular DNA molecule specifies the genetic information: this is comparable to a sequence of letters spelling out a passage of text. Before a cell divides through mitosis, the DNA is copied, so that each of the resulting two cells will inherit the DNA sequence. A portion of a DNA molecule that specifies a single functional unit is called a gene. Within cells, the long strands of DNA form condensed structures called chromosomes. Organisms inherit genetic material from their parents in the form of homologous chromosomes, containing a unique combination of DNA sequences that code for genes; the specific location of a DNA sequence within a chromosome is known as a locus. If the DNA sequence at a particular locus varies between individuals, the different forms of this sequence are called alleles. DNA sequences can change through mutations.
If a mutation occurs within a gene, the new allele may affect the trait that the gene controls, altering the phenotype of the organism. However, while this simple correspondence between an allele and a trait works in some cases, most traits are more complex and are controlled by multiple interacting genes within and among organisms. Developmental biologists suggest that complex interactions in genetic networks and communication among cells can lead to heritable variations that may underlie some of the mechanics in developmental plasticity and canalization. Recent findings have confirmed important examples of heritable changes that cannot be explained by direct agency of the DNA molecule; these phenomena are classed as epigenetic inheritance systems that are causally or independently evolving over genes. Research into modes and mechanisms of epigenetic inheritance is still in its scientific infancy, this area of research has attracted much recent activity as it broadens the scope of heritability and evolutionary biology in general.
DNA methylation marking chromatin, self-sustaining metabolic loops, gene silencing by RNA interference, the three dimensional conformation of proteins are areas where epigenetic inheritance systems have been discovered at the organismic level. Heritability may occur at larger scales. For example, ecological inheritance through the process of niche construction is defined by the regular and repeated activities of organisms in their environment; this generates a legacy of effect that modifies and feeds back into the selection regime of subsequent generations. Descendants inherit genes plus environmental characteristics generated by the ecological actions of ancestors. Other examples of heritability in evolution that are not under the direct control of genes include the inheritance of cultural traits, group heritability, symbiogenesis; these examples of heritability that operate above the gene are covered broadly under the title of multilevel or hierarchical selection, a subject of intense debate in the history of evolutionary science.
When Charles Darwin proposed his theory of evolution in 1859, one of its major problems was the lack of an underlying mechanism for heredity. Darwin believed in the inheritance of acquired traits. Blending inheritance would lead to uniformity across populations in only a few generations and would remove variation from a population on which natural selection could act; this led to Darwin adopting some Lamarckian ideas in editions of On the Origin of Species and his biological works. Darwin's primary approach to heredity was to outline how it appeared to work rather than suggesting mechanisms. Darwin's initial model of heredity was adopted by, heavily modified by, his cousin Francis Galton, who laid the framework for the biometric school of heredity. Galton found no evidence to support the aspects of Darwin's pangenesis model, which relied on acquired traits; the inheritance of acquired traits was shown to have little basis in the 1880s when August Weismann cut the tails off many generations of mice and found that their offspring continued to develop tails.
Scientists in Antiquity had a variety of ideas about heredity: Theophrastus proposed that male flowers caused f
In the fields of molecular biology and genetics, a genome is the genetic material of an organism. It consists of DNA; the genome includes both the genes and the noncoding DNA, as well as mitochondrial DNA and chloroplast DNA. The study of the genome is called genomics; the term genome was created in 1920 by Hans Winkler, professor of botany at the University of Hamburg, Germany. The Oxford Dictionary suggests the name is a blend of the words chromosome. However, see omics for a more thorough discussion. A few related -ome words existed, such as biome and rhizome, forming a vocabulary into which genome fits systematically. A genome sequence is the complete list of the nucleotides that make up all the chromosomes of an individual or a species. Within a species, the vast majority of nucleotides are identical between individuals, but sequencing multiple individuals is necessary to understand the genetic diversity. In 1976, Walter Fiers at the University of Ghent was the first to establish the complete nucleotide sequence of a viral RNA-genome.
The next year, Fred Sanger completed the first DNA-genome sequence: Phage Φ-X174, of 5386 base pairs. The first complete genome sequences among all three domains of life were released within a short period during the mid-1990s: The first bacterial genome to be sequenced was that of Haemophilus influenzae, completed by a team at The Institute for Genomic Research in 1995. A few months the first eukaryotic genome was completed, with sequences of the 16 chromosomes of budding yeast Saccharomyces cerevisiae published as the result of a European-led effort begun in the mid-1980s; the first genome sequence for an archaeon, Methanococcus jannaschii, was completed in 1996, again by The Institute for Genomic Research. The development of new technologies has made genome sequencing cheaper and easier, the number of complete genome sequences is growing rapidly; the US National Institutes of Health maintains one of several comprehensive databases of genomic information. Among the thousands of completed genome sequencing projects include those for rice, a mouse, the plant Arabidopsis thaliana, the puffer fish, the bacteria E. coli.
In December 2013, scientists first sequenced the entire genome of a Neanderthal, an extinct species of humans. The genome was extracted from the toe bone of a 130,000-year-old Neanderthal found in a Siberian cave. New sequencing technologies, such as massive parallel sequencing have opened up the prospect of personal genome sequencing as a diagnostic tool, as pioneered by Manteia Predictive Medicine. A major step toward that goal was the completion in 2007 of the full genome of James D. Watson, one of the co-discoverers of the structure of DNA. Whereas a genome sequence lists the order of every DNA base in a genome, a genome map identifies the landmarks. A genome map is less detailed than aids in navigating around the genome; the Human Genome Project was organized to sequence the human genome. A fundamental step in the project was the release of a detailed genomic map by Jean Weissenbach and his team at the Genoscope in Paris. Reference genome sequences and maps continue to be updated, removing errors and clarifying regions of high allelic complexity.
The decreasing cost of genomic mapping has permitted genealogical sites to offer it as a service, to the extent that one may submit one's genome to crowdsourced scientific endeavours such as DNA. LAND at the New York Genome Center, an example both of the economies of scale and of citizen science. Viral genomes can be composed of either RNA or DNA; the genomes of RNA viruses can be either single-stranded or double-stranded RNA, may contain one or more separate RNA molecules. DNA viruses can have either double-stranded genomes. Most DNA virus genomes are composed of a single, linear molecule of DNA, but some are made up of a circular DNA molecule. Prokaryotes and eukaryotes have DNA genomes. Archaea have a single circular chromosome. Most bacteria have a single circular chromosome. If the DNA is replicated faster than the bacterial cells divide, multiple copies of the chromosome can be present in a single cell, if the cells divide faster than the DNA can be replicated, multiple replication of the chromosome is initiated before the division occurs, allowing daughter cells to inherit complete genomes and partially replicated chromosomes.
Most prokaryotes have little repetitive DNA in their genomes. However, some symbiotic bacteria have reduced genomes and a high fraction of pseudogenes: only ~40% of their DNA encodes proteins; some bacteria have auxiliary genetic material part of their genome, carried in plasmids. For this, the word genome should not be used as a synonym of chromosome. Eukaryotic genomes are composed of one or more linear DNA chromosomes; the number of chromosomes varies from Jack jumper ants and an asexual nemotode, which each have only one pair, to a fern species that has 720 pairs. A typical human cell has two copies of each of 22 autosomes, one inherited from each parent, plus two sex chromosomes, making it diploid. Gametes, such as ova, sperm and pollen, are haploid, meaning they carry only one copy of each chromosome. In addition to the chromosomes in the nucleus, organelles such as the chloroplasts and mitochondria have their own DNA. Mitochondria are sometimes said to have their own genome referred to as the "mitochondrial genome".
The DNA found within the chloroplast may be referred to as the "plastome". Like the bacteria they originated from and chloroplasts have a circular chromosome
FMR1 is a human gene that codes for a protein called fragile X mental retardation protein, or FMRP. This protein, most found in the brain, is essential for normal cognitive development and female reproductive function. Mutations of this gene can lead to fragile X syndrome, intellectual disability, premature ovarian failure, Parkinson's disease, developmental delays and other cognitive deficits; the FMR1 premutation is associated with a wide spectrum of clinical phenotypes that affect more than two million people worldwide. FMRP has a diverse array of functions throughout different areas of the neuron. FMRP has been suggested to play roles in nucleocytoplasmic shuttling of mRNA, dendritic mRNA localization, synaptic protein synthesis. Studies of Fragile X syndrome have aided in the understanding of the functionality of FMRP through the observed effects of FMRP loss on neurons. A mouse model of fragile X mental retardation implicated the involvement of FMRP in synaptic plasticity. Synaptic plasticity requires the production of new proteins in response to activation of synaptic receptors.
It is the production of proteins in response to stimulation, hypothesized to allow for the permanent physical changes and altered synaptic connections that are linked with the processes of learning and memory. Group 1 metabotropic glutamate receptor signaling has been implicated in playing an important role in FMRP-dependent synaptic plasticity. Post-synaptic mGluR stimulation results in the up-regulation of protein synthesis through a second messenger system. A role for mGluR in synaptic plasticity is further evidenced by the observation of dendritic spine elongation following mGluR stimulation. Furthermore, mGluR activation results in the synthesis of FMRP near synapses; the produced FMRP associates with polyribosomal complexes after mGluR stimulation, proposing the involvement of fragile X mental retardation protein in the process of translation. This further advocates a role for FMRP in synaptic protein synthesis and the growth of synaptic connections; the loss of FMRP results in an abnormal dendritic spine phenotype.
Deletion of the FMR1 gene in a sample of mice resulted in an increase in spine synapse number. The proposed mechanism of FMRP's effect upon synaptic plasticity are through its role as a negative regulator of translation. FMRP is an RNA-binding protein; the RNA-binding abilities of FMRP are dependent upon its KH RGG boxes. The KH domain is a conserved motif. Mutagenesis of this domain resulted in impaired FMRP binding to RNA. FMRP has been shown to inhibit translation of mRNA. Mutation of the FMRP protein resulted in the inability to repress translation as opposed to the wild-type counterpart, able to do so; as mentioned, mGluR stimulation is associated with increased FMRP protein levels. In addition, mGluR stimulation results in increased levels of FMRP target mRNAs. A study found basal levels of proteins encoded by these target mRNAs to be elevated and improperly regulated in FMRP deficient mice. FMRP translation repression acts by inhibiting the initiation of translation. FMRP directly binds CYFIP1, which in turn binds the translation initiation factor eIF4E.
The FMRP-CYFIP1 complex prohibits eIF4E-dependent initiation, thereby acting to repress translation. When applied to the observed phenotype in fragile X Syndrome, the excess protein levels and reduction of translational control can be explained by the loss of translational repression by FMRP in fragile X syndrome. FMRP acts to control translation of a large group of target mRNAs; the protein has been shown to repress the translation of target mRNAs at synapses, including those encoding the cytoskeletal proteins Arc/Arg3.1 and MAP1B, the CaM kinase II. In addition, FMRP binds PSD-95 and GluR1/2 mRNAs; these FMRP-binding mRNAs play significant roles in neuronal plasticity. FMRP translational control has been shown to be regulated by mGluR signaling. MGluR stimulation may result in the transportation of mRNA complexes to synapses for local protein synthesis. FMRP granules have been shown to localize with MAP1B mRNA and ribosomal RNA in dendrites, suggesting this complex as a whole may need to be transported to dendrites for local protein synthesis.
In addition, microtubules were found to be a necessary component for the mGluR-dependent translocation of FMRP into dendrites. FMRP may play an additional role in local protein synthesis by aiding in the association of mRNA cargo and microtubules. Thus, FMRP is able to regulate transport efficacy, as well as repression of translation during transport. FMRP synthesis and proteolysis occur in response to mGluR signaling, suggesting an dynamic role of the translational regulator; the FMR1 gene contains a repeated CGG trinucleotide. In most people, the CGG segment is repeated 5-44 times. Higher numbers of repeats of the CGG segment are associated with impaired cognitive and reproductive function. If a person has 45-54 repeats this is considered the “gray zone” or borderline risk, 55-200 repeats is called premutation, more than 200 repeats is considered a full mutation of the FMR1 gene according to the American College of Medical Genetics and Genomics; the first complete DNA sequence of the repeat expansion in someone with the full mutation was generated by scientists in 2012 using SMRT sequencing.
This is an example of a Trinucleotide repeat disorder. Trinucleotide repeat expansion is a consequence of strand slippage either during DNA
The X chromosome is one of the two sex-determining chromosomes in many organisms, including mammals, is found in both males and females. It is a part of the XY sex-determination X0 sex-determination system; the X chromosome was named for its unique properties by early researchers, which resulted in the naming of its counterpart Y chromosome, for the next letter in the alphabet, following its subsequent discovery. It was first noted. Henking was studying the testicles of Pyrrhocoris and noticed that one chromosome did not take part in meiosis. Chromosomes are so named because of their ability to take up staining. Although the X chromosome could be stained just as well as the others, Henking was unsure whether it was a different class of object and named it X element, which became X chromosome after it was established that it was indeed a chromosome; the idea that the X chromosome was named after its similarity to the letter "X" is mistaken. All chromosomes appear as an amorphous blob under the microscope and only take on a well defined shape during mitosis.
This shape is vaguely X-shaped for all chromosomes. It is coincidental that the Y chromosome, during mitosis, has two short branches which can look merged under the microscope and appear as the descender of a Y-shape, it was first suggested that the X chromosome was involved in sex determination by Clarence Erwin McClung in 1901. After comparing his work on locusts with Henking's and others, McClung noted that only half the sperm received an X chromosome, he called this chromosome an accessory chromosome, insisted that it was a proper chromosome, theorized that it was the male-determining chromosome. Luke Hutchison noticed that a number of possible ancestors on the X chromosome inheritance line at a given ancestral generation follows the Fibonacci sequence. A male individual has an X chromosome, which he received from his mother, a Y chromosome, which he received from his father; the male counts as the "origin" of his own X chromosome, at his parents' generation, his X chromosome came from a single parent.
The male's mother received one X chromosome from her mother, one from her father, so two grandparents contributed to the male descendant's X chromosome. The maternal grandfather received his X chromosome from his mother, the maternal grandmother received X chromosomes from both of her parents, so three great-grandparents contributed to the male descendant's X chromosome. Five great-great-grandparents contributed to the male descendant's X chromosome, etc; the X chromosome in humans spans more than 153 million base pairs. It represents about 800 protein-coding genes compared to the Y chromosome containing about 70 genes, out of 20,000–25,000 total genes in the human genome; each person has one pair of sex chromosomes in each cell. Females have two X chromosomes, whereas males have one Y chromosome. Both males and females retain one of their mother's X chromosomes, females retain their second X chromosome from their father. Since the father retains his X chromosome from his mother, a human female has one X chromosome from her paternal grandmother, one X chromosome from her mother.
This inheritance pattern follows the Fibonacci numbers at a given ancestral depth. Genetic disorders that are due to mutations in genes on the X chromosome are described as X linked. If X chromosome has a genetic disease gene, it always causes illness in male patients, since men have only one X chromosome and therefore only one copy of each gene. Females, may stay healthy and only be carrier of genetic illness, since they have another X chromosome and possibility to have healthy gene copy. For example hemophilia and red-green colorblindness run in family this way; the X chromosome carries hundreds of genes but few, if any, of these have anything to do directly with sex determination. Early in embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated in nearly all somatic cells; this phenomenon is called X-inactivation or Lyonization, creates a Barr body. If X-inactivation in the somatic cell meant a complete de-functionalizing of one of the X-chromosomes, it would ensure that females, like males, had only one functional copy of the X chromosome in each somatic cell.
This was assumed to be the case. However, recent research suggests that the Barr body may be more biologically active than was supposed; the partial inactivation of the X-chromosome is due to repressive heterochromatin that compacts the DNA and prevents the expression of most genes. Heterochromatin compaction is regulated by Polycomb Repressive Complex 2; the following are some of the gene count estimates of human X chromosome. Because researchers use different approaches to genome annotation their predictions of the number