User talk:Nithinkcgowda

Chromosome[edit] A chromosome is an organized structure of DNA and protein that is found in nucleus of the cell. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. Chromosomes vary widely between different organisms. The DNA molecule may be circular or linear, and can be composed of 10,000 to 1,000,000,000 nucleotides in a long chain. Typically, eukaryotic cells (cells with nuclei) have large linear chromosomes and prokaryotic cells (cells without defined nuclei) have smaller circular chromosomes, although there are many exceptions to this rule. Also, cells may contain more than one type of chromosome; for example, mitochondria in most eukaryotes and chloroplasts in plants have their own small chromosomes.[2]

In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure called chromatin. This allows the very long DNA molecules to fit into the cell nucleus. The structure of chromosomes and chromatin varies through the cell cycle. Chromosomes are the essential unit for cellular division and must be replicated, divided, and passed successfully to their daughter cells so as to ensure the genetic diversity and survival of their progeny. Chromosomes may exist as either duplicated or unduplicated. Unduplicated chromosomes are single linear strands, whereas duplicated chromosomes (copied during synthesis phase) contain two copies joined by a centromere. Compaction of the duplicated chromosomes during mitosis and meiosis results in the classic four-arm structure (pictured to the right). Chromosomal recombination plays a vital role in genetic diversity. If these structures are manipulated incorrectly, through processes known as chromosomal instability and translocation, the cell may undergo mitotic catastrophe and die, or it may unexpectedly evade apoptosis leading to the progression of cancer. In practice "chromosome" is a rather loosely defined term. In prokaryotes and viruses, the term genophore is more appropriate when no chromatin is present. However, a large body of work uses the term chromosome regardless of chromatin content. In prokaryotes, DNA is usually arranged as a circle, which is tightly coiled in on itself, sometimes accompanied by one or more smaller, circular DNA molecules called plasmids. These small circular genomes are also found in mitochondria and chloroplasts, reflecting their bacterial origins. The simplest genophores are found in viruses: these DNA or RNA molecules are short linear or circular genophores that often lack structural proteins. The word chromosome comes from the Greek χρῶμα (chroma, colour) and σῶμα (soma, body) due to their property of being very strongly stained by particular dyes.[3]

Chromatin[edit] Chromatin is the combination of DNA, histone, and other proteins that make up chromosomes. It is found inside the nuclear envelope of eukaryotic cells. It is divided between heterochromatin (condensed) and euchromatin (extended) forms. The functions of chromatin are to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis, and to control gene expression and DNA replication. Changes in chromatin structure are affected by chemical modifications of histone proteins, such as methylation and acetylation, and by other DNA-binding proteins.

Packaging of DNA in chromatin[edit] Chromatin undergoes various forms of change in its structure. Histone proteins, the foundation blocks of chromatin, are modified by various post-translational modification to alter DNA packing. Acetylation results in the loosening of chromatin and lends itself to replication and transcription. When certain residues are methylated they hold DNA together strongly and restrict access to various enzymes. A recent study showed that there is a bivalent structure present in the chromatin: methylated lysine residues at location 4 and 27 on histone 3. It is thought that this may be involved in development; there is more methylation of lysine 27 in embryonic cells than in differentiated cells, whereas lysine 4 methylation positively regulates transcription by recruiting nucleosome remodeling enzymes and histone acetylases[4].[5]

Polycomb-group proteins play a role in regulating genes through modulation of chromatin structure.[6]

Chromatin and Watson/Crick base pairing[edit] Crick and Watson's famous structure of DNA (called B-DNA) is only one of three possible structural forms.

For the C-N bond between a base and its sugar there are two different conformations. The anti-conformation occurs in all A- and B-DNAs as well as in Z-DNA where a Cytosine is present. In case of a Guanine Z-DNA takes the syn-conformation. The periodic change between a purine and pyrimidine along the strand of a Z-DNA accomplishes the alternating syn-anti-conformation characteristic of the zigzag structure of the Z-DNA helix.

A cartoon representation of the nucleosome structure. From pdb. Histone:The DNA binding protein[edit] Histones were discovered in 1884 by Albrecht Kossel. The word "histone" dates from the late 19th century and is from the German "Histon", of uncertain origin: perhaps from Greek histanai or from histos. Until the early 1990s, histones were dismissed by most as inert packing material for eukaryotic nuclear DNA, based in part on the "ball and stick" models of Mark Ptashne and others who believed transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, as is the case in bacteria. During the 1980s, work by Michael Grunstein demonstrated that eukaryotic histones repress gene transcription, and that the function of transcriptional activators is to overcome this repression. We now know that histones play both positive and negative roles in gene expression, forming the basis of the histone code. The discovery of the H5 histone appears to date back to 1970's, and in classification it has been grouped with H1.[7]

Histones are found in the nuclei of eukaryotic cells, and in certain Archaea, namely Euryarchaea, but not in bacteria. Archaeal histones may well resemble the evolutionary precursors to eukaryotic histones. Histone proteins are among the most highly conserved proteins in eukaryotes, emphasizing their important role in the biology of the nucleus.:939 In contrast mature sperm cells largely use protamines to package their genomic DNA, most likely because this allows them to achieve an even higher packaging ratio. Core histones are highly conserved proteins, that is, there are very few differences among the amino acid sequences of the histone proteins of different species. Linker histone usually has more than one form within a species and is also less conserved than the core histones. There are some variant forms in some of the major classes. They share amino acid sequence homology and core structural similarity to a specific class of major histones but also have their own feature that is distinct from the major histones. These minor histones usually carry out specific functions of the chromatin metabolism. For example, histone H3-like CenpA is a histone only associated with the centromere region of the chromosome. Histone H2A variant H2A.Z is associated with the promoters of actively transcribed genes and also involved in the prevention of the spread of silent heterochromatin. Another H2A variant H2A.X binds to the DNA with double strand breaks and marks the region undergoing DNA repair. Histone H3.3 is associated with the body of actively transcribed genes.[8][9]

The nucleosome and "beads-on-a-string"[edit] The basic repeat element of chromatin is the nucleosome, interconnected by sections of linker DNA, a far shorter arrangement than pure DNA in solution.

In addition to the core histones, there is the linker histone, H1, which contacts the exit/entry of the DNA strand on the nucleosome. The nucleosome core particle, together with histone H1, is known as a chromatosome. Nucleosomes, with about 20 to 60 base pairs of linker DNA, can form, under non-physiological conditions, an approximately 10 nm "beads-on-a-string" fibre.

The nucleosomes bind DNA non-specifically, as required by their function in general DNA packaging. There are, however, large DNA sequence preferences that govern nucleosome positioning. This is due primarily to the varying physical properties of different DNA sequences: For instance, adenosine and thymine are more favorably compressed into the inner minor grooves. This means nucleosomes can bind preferentially at one position approximately every 10 base pairs (the helical repeat of DNA)- where the DNA is rotated to maximise the number of A and T bases that will lie in the inner minor groove.

What is a Nucleosome? Nucleosomes are the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound around a histone protein core. This structure is often compared to thread wrapped around a spool. Nucleosomes form the fundamental repeating units of eukaryotic chromatin, which is used to pack the large eukaryotic genomes into the nucleus while still ensuring appropriate access to it (in mammalian cells approximately 2 m of linear DNA have to be packed into a nucleus of roughly 10 µm diameter). Nucleosomes are folded through a series of successively higher order structures to eventually form a chromosome; this both compacts DNA and creates an added layer of regulatory control which ensures correct gene expression. Nucleosomes are thought to carry epigenetically inherited information in the form of covalent modifications of their core histones. The nucleosome hypothesis was proposed by Don and Ada Olins in 1974 and Roger Kornberg. The nucleosome core particle consists of approximately 147 base pairs of DNA wrapped in 1.67 left-handed superhelical turns around a histone octamer consisting of 2 copies each of the core histones H2A, H2B, H3, and H4. Core particles are connected by stretches of "linker DNA", which can be up to about 80 bp long. Technically, a nucleosome is defined as the core particle plus one of these linker regions; however the word is often synonymous with the core particle. Linker histones such as H1 and its isoforms are involved in chromatin compaction and sit at the base of the nucleosome near the DNA entry and exit binding to the linker region of the DNA. Non-condensed nucleosomes without the linker histone resemble "beads on a string of DNA" under an electron microscope. In contrast to most eukaryotic cells, mature sperm cells largely use protamines to package their genomic DNA, most likely to achieve an even higher packaging ratio.Histone equivalents and a simplified chromatin structure have also been found in Archea, proving that eukaryotes are not the only organisms that use nucleosomes. 30 nm chromatin fibre[edit]

Two proposed structures of the 30nm chromatin filament. Left: 1 start helix "solenoid" structure. Right: 2 start loose helix structure. Note: the histones are omitted in this diagram - only the DNA is shown. With addition of H1, the "beads-on-a-string" structure in turn coils into a 30 nm diameter helical structure known as the 30 nm fibre or filament. The precise structure of the chromatin fibre in the cell is not known in detail, and there is still some debate over this.

This level of chromatin structure is thought to be the form of euchromatin, which contains actively transcribed genes. EM studies have demonstrated that the 30 nm fibre is highly dynamic such that it unfolds into a 10 nm fiber ("beads-on-a-string") structure when transversed by an RNA polymerase engaged in transcription.

Four proposed structures of the 30 nm chromatin filament for DNA repeat length per nucleosomes ranging from 177 to 207 bp. Linker DNA in yellow and nucleosomal DNA in pink. The existing models commonly accept that the nucleosomes lie perpendicular to the axis of the fibre, with linker histones arranged internally. A stable 30 nm fibre relies on the regular positioning of nucleosomes along DNA. Linker DNA is relatively resistant to bending and rotation. This makes the length of linker DNA critical to the stability of the fibre, requiring nucleosomes to be separated by lengths that permit rotation and folding into the required orientation without excessive stress to the DNA. In this view, different length of the linker DNA should produce different folding topologies of the chromatin fiber. Recent theoretical work, based on electron-microscopy images[10] of reconstituted fibers support this view.[11]

Spatial organization of chromatin in the cell nucleus[edit] The layout of the genome within the nucleus is not random - specific regions of the genome have a tendency to be found in certain spaces. Specific regions of the chromatin are enriched at the nuclear membrane, while other regions are bound together by protein complexes. The layout of this is not, however, well characterised apart from the compaction of one of the two X chromosomes in mammalian females into the Barr body. This serves the role of permanently deactivating these genes, which prevents females getting a 'double dose' relative to males. The extent to which the inactive X is actually compacted is a matter of some controversy.

Scheme of the X chromatid

Human Y-chromatid Human chromosomes[edit] Chromosomes can be divided into two types—autosomes, and sex chromosomes. Certain genetic traits are linked to your sex, and are passed on through the sex chromosomes. The autosomes contain the rest of the genetic hereditary information. All act in the same way during cell division. Human cells have 23 pairs of large linear nuclear chromosomes, (22 pairs of autosomes and one pair of sex chromosomes) giving a total of 46 per cell. In addition to these, human cells have many hundreds of copies of the mitochondrial genome. Sequencing of the human genome has provided a great deal of information about each of the chromosomes. Below is a table compiling statistics for the chromosomes, based on the Sanger Institute's human genome information in the Vertebrate Genome Annotation (VEGA) database.[12] Number of genes is an estimate as it is in part based on gene predictions. Total chromosome length is an estimate as well, based on the estimated size of unsequenced heterochromatin regions.

An autosome is a chromosome that is not a sex chromosome; that is to say, there is an equal number of copies of the chromosome in males and females.[13] For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X chromosome and Y chromosome. So, humans have 23 pairs of chromosomes.

Sex chromosomes The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals (the other is the Y chromosome). It is a part of the XY sex-determination system and 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, after it was discovered later.

The Y-chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y-chromosome is composed of about 60 million base pairs. DNA in the Y-chromosome is passed from father to son, and Y-DNA analysis may thus be used in genealogy research.````