The document discusses DNA and chromosomes. It describes how DNA carries genetic instructions in genes and is organized into chromosomes. The structure of DNA was determined in 1953 to be a double helix with two strands bonded together. Chromosomes contain DNA and protein, and become visible during cell division. DNA is highly condensed and packaged into chromosomes to fit inside cells. The structure of DNA allows hereditary information to be stored and passed down from parent to daughter cells and between generations.
The document discusses DNA and chromosomes. It describes how DNA carries genetic instructions in genes and is organized into chromosomes. The structure of DNA was determined in 1953 to be a double helix with two strands bonded together. Chromosomes contain DNA and protein, and become visible during cell division. DNA is highly condensed and packaged into chromosomes to fit inside cells. The structure of DNA allows hereditary information to be stored and passed down from parent to daughter cells and between generations.
The document discusses DNA and chromosomes. It describes how DNA carries genetic instructions in genes and is organized into chromosomes. The structure of DNA was determined in 1953 to be a double helix with two strands bonded together. Chromosomes contain DNA and protein, and become visible during cell division. DNA is highly condensed and packaged into chromosomes to fit inside cells. The structure of DNA allows hereditary information to be stored and passed down from parent to daughter cells and between generations.
retrieve, and translate the genetic instructions this hereditary information is passed on from a cell to its daughter cells at cell division & from generation to generation in multicellular organisms through the reproductive cells. Instructions are stored within every living cell in its genesthe information-containing elements. The totality of this information in each cell is called its genome. In the 1940srecognition that deoxyribonucleic acid (DNA) was the likely carrier of this genetic information was done. In 1953structure of DNA was determined by James Watson and Francis Crick.
The structure and function
of DNA Chromosomesthreadlike structures in the
nucleus of the eucaryotic cellbecome visible
as the cell begins to dividecontain both DNA and protein DNAcarries the hereditary information & protein components of chromosomes function largely to package and control the enormously long DNA molecules Early in the 1950sDNA was examined by Xray diffraction analysisresults indicated that DNA is composed of two strands wound into a helix
Dividing cell
Non-dividing cell
Fig. Chromosomes become visible as
cells prepare to divide.
A DNA molecule consists of two
complementary chains of nucleotides Deoxyribonucleic acid (DNA)two long polynucleotide chains/strandsEach is composed of four types of nucleotide subunits, and the two chains are held together by hydrogen bonds between the base portions of the nucleotides. Nucleotidescomposed of a five-carbon sugar (deoxyribose) to which are attached one or more phosphate groups and a nitrogen-containing base (adenine (A), cytosine (C), guanine (G), or thymine (T)nucleotides are covalently linked together in a chain through the sugars and phosphates, which thus form a backbone of alternating sugar
Fig. DNA is made of four nucleotide
building blocks.
Fig. DNA double helix
Chemical polarity in DNA strandthe two ends of
the chain, one will have a 3 hydroxyl & the other, a 5 phosphate thus polarity is indicated by referring to one end as the 3 end and the other as the 5 end i.e helix run antiparallel to each other. Two polynucleotide chains in the DNA double helix held together by hydrogen-bonding between the bases on the different strands, bases are therefore on the inside of the helix, with the sugar phosphate backbones on the outside A always pairs with T, and G always pairs with C i.e. a two-ring base (purine) is paired with a singlering base (a pyrimidine)Each pair is called a base paireach pair is of similar width thus holding the sugarphosphate backbones an equal distance
The antiparallel strandstwist around
each other to form a double helix containing 10 base pairs per helical turn. Double helix base-pairing requirements is that each strand of a DNA molecule contains a sequence of nucleotides that is exactly complementary to the nucleotide sequence of its partner strandan A always matches a T on the opposite strand, and a C always
The structure of DNA provides a
mechanism for heredity DNA encodes information in the order, or sequence, of the nucleotides along each strand. Each baseA, C, T, or Gcan be considered as a letter that is used to spell out biological messages in the chemical structure of the DNA. Organisms differ because of their nucleotide sequences and thus carry different biological messages. The DNA messages encode proteins.
The structure of eucaryotic
chromosomes Each human cell contains about 2 m of DNA; yet the cell nucleus is only 58 mm in diameter. In eucaryotic cells, very long double-stranded DNA molecules are packaged into structures called chromosomes (fit readily inside the nucleus & can be easily apportioned between the two daughter cells at cell division. Packaging DNAaccomplished by specialized proteins that bind to and fold the DNA in such a way that allows it to remain accessible to all of the enzymes and other proteins that replicate it, repair it, and direct the expression of its genes. Bacteriacarry their genes on a single, circular DNA moleculeassociated with proteins that condense DNA, but these proteins differ from the ones that package eucaryotic DNAthis procaryotic DNA does not have the same structure as eucaryotic chromosomes.
Eucaryotic DNA is packaged into
multiple chromosomes DNAdistributed among a set of different chromosomes. The human genome3.2 x 109 nucleotides parceled out into 24 chromosomes. Each chromosomeconsists of a single enormously long, linear DNA molecule associated with proteins that fold and pack the fine thread of DNA. The complex of DNA and protein is called chromatin. Human cells (with the exception of the germ cells & highly specialized cells that lack DNA entirely) contain two copies of each chromosome, one inherited from the mother and one from the father. The maternal and paternal chromosomes of a pair are called homologous chromosomes (homologs).
The only non-homologous chromosome pairs
sex chromosomes in males, where a Y chromosome is inherited from the father and an X chromosome from the mother. Human chromosomes can be distinguished each chromosome can be painted a different color using sets of chromosome-specific DNA molecules coupled to different fluorescent dyes. This involves the technique of DNA hybridization OR stain the chromosomes with dyes that bind to certain types of DNA sequences. Human karyotypeA display of the full set of 46 human chromosomes
Chromosomes contain long strings
of genes Genesegment of DNA that contains the instructions for making a particular proteinsome genes direct the production of an RNA molecule, instead of a protein which perform a diverse set of structural and catalytic functions in the cell like proteins. Correlation exists between the complexity of an organism and the number of genesless than 500 for a simple bacterium to about 25,000 for humans. Chromosomes from many eucaryotes (including humans) contain, in addition to genes, a large excess of interspersed DNA, the majority of which does not seem to carry critical information. This DNA is sometimes called junk DNA, because its usefulness to the cell has not yet been clearly demonstrated. Comparisons of the genome sequences from many different species reveals that a portion of this extra DNA is highly conserved among related species
Although gene number is roughly correlated with
species complexity, there is no simple relationship between gene number, chromosome number, and total genome size. The human genome, for example, is 200 times larger than that of the yeast S. cerevisiae, but 30 times smaller than that of some plants and at least 60 times smaller than some species of amoeba. Furthermore, how the DNA is apportioned over chromosomes also differs from one species to another. Humans have 46 chromosomes, but a species of small deer has only 6, while some carp species have more than 100. Even closely related species with similar genome sizes can have very different numbers and sizes of chromosomes.
Chromosomes exist in different
states throughout the life of a cell To form a functional chromosomea DNA molecule must be able to be replicated, and the replicated copies must be separated and partitioned reliably into daughter cells at each cell division. These processes occur through an ordered series of events, known collectively as the cell cycle. During interphasethe chromosomes are extended as long, thin, tangled
interphas e chromoso me INTERPHASE
M PHASE
INTERPHASE
Fig: The replication and segregation of
chromosomes occurs through an ordered cell cycle
One type of nucleotide sequence acts as
a replication origin, where duplication of the DNA begins. Eucaryotic chromosomes contain many replication origins. Another DNA sequence forms the telomeres found at each of the two ends of a chromosome. Telomeres contain repeated nucleotide sequences that enable the ends of chromosomes to be replicatedalso cap the end of the chromosome, preventing it from being mistaken by the cell as a broken DNA
M phasethe DNA coils up (compact
structure) ultimately forming mitotic chromosomes, state in which chromosomes are most easily visualized. Duplicated chromosomes can be readily separated when the cell divides. Once the chromosomes have condensed, it is the presence of the third specialized DNA sequence, the centromere, that allows one copy of each duplicated chromosome to be apportioned to each
Fig. Three DNA sequence elements are needed to
produce a eucaryotic chromosome that can be replicated and then segregated at mitosis.
Interphase chromosomes are
organized within the nucleus Nuclear laminaa network of protein filaments that forms a thin layer underlying and the inner nuclear membrane. Inside the nucleusthe interphase chromosomesare nonetheless organized in various waysFirst, each tends to occupy a particular region of the nucleus, In addition, specific regions of chromosomes are attached to sites on the nuclear envelope or the nuclear lamina. Example of chromosome organization in the interphase nucleus is the nucleolussite where the parts of the different chromosomes carrying genes for ribosomal RNA cluster together. Here, ribosomal RNAs are synthesized and combined with proteins to form ribosomes, the cells protein-synthesizing machines
The DNA in chromosomes is highly
condensed Human Chromosome 22contains about 48 million nucleotide pairs; stretched out end-to-end, its DNA would extend about 1.5 cm. Yet, during mitosis, Chromosome 22 measures only about 2 mm in length that is, nearly 10,000 times more compact than the DNA in its extended form. This remarkable feat of compression is performed by proteins that coil and fold the DNA into higher and higher levels of organization. The DNA of interphase chromosomes, although less condensed than that of mitotic chromosomes still packed tightly, with a compaction ratio of about 500-fold. Chromosome packaging must be flexible enough to allow rapid, localized, ondemand access to the DNA.
Nucleosomes are the basic units of
eucaryotic chromosome structure In eucaryotic chromosomes, the proteins that bind to the DNAthe histones and the non-histone chromosomal proteins. The complex of both classes of protein with nuclear DNA is called chromatin. Histonesresponsible for the chromatin packing, the nucleosome. When interphase nuclei are broken openmost of the chromatin is in the form of fibersIf this is subjected to treatments that cause it to unfold partially, it can then be seen as a series of beads on a string. The string is DNA, and each bead is a nucleosome core particle that consists of DNA wound around a core of proteins formed from histones.
Fig. this electron micrograph shows a
length of a chromatin fiber that has been experimentally unpacked, or decondensed, after isolation to show the
The structure of the nucleosome core particle was
determinedafter digestion, only the exposed DNA b/w the core particles, the linker DNA. Nucleosome core particlecomplex of eight histone proteinstwo molecules each of histones H2A, H2B, H3, and H4and the double-stranded DNA, 147 nucleotide pairs long, that winds around this histone octamer making 1.7 turns in a left-handed coil. The linker DNAcan vary in length from a few nucleotide pairs up to about 80. The formation of nucleosomes converts a DNA molecule into a chromatin thread approximately one-third of its initial length, and it provides the first level of DNA packing. All four of the histonessmall proteins with a high proportion of positively charged amino acids (lysine and arginine).
The positive charges help the histones bind
tightly to the negatively charged sugar phosphate backbone of DNA. Each of the core histones also has a long N-terminal amino acid tail, which extends out from the nucleosome core particle These histone tails are subject to several types of covalent chemical modifications that control many aspects of chromatin structure. The histoneshighly conserved of all known eucaryotic proteins: there are only two differences between the amino acid sequences of histone H4 from peas and cows, for example. This extreme evolutionary conservation reflects the vital role of histones in controlling eucaryotic chromosome structure.
an H3 Histone tail
DNA double helix
Fig. The structure of the nucleosome core
particle, as determined by X-ray diffraction analysis, reveals how DNA is tightly
Chromosome packing occurs on
multiple levels The nucleosomes are further packed upon one another to generate a more compact structure, the 30-nm fiber. This packing depends on a fifth histone called histone H1, which is thought to pull the nucleosomes together into a regular repeating array. This linker histone changes the path the DNA takes as it exits the nucleosome core, allowing it to form a more compact structure. The 30-nm fiber is folded into a series of loops, and that these loops are further condensed to produce the interphase chromosome. Finally, this compact string of loops is thought to undergo at least one more level of packing to form the mitotic chromosome.
Fig. Chromatin isolated directly from
an interphase nucleus appears in the electron microscope as threads 30-nm thick
Fig. DNA packing occurs on several
levels in chromosomes
The regulation of chromosome
structure Changes in nucleosome Structure allow access to DNA: chromatin-remodeling complexesprotein machines that use the energy of ATP hydrolysis to change the position of the DNA wrapped around nucleosomes. By pushing on the tightly bound DNA as they move along, these complexes can loosen (decondense) the underlying DNA, making it more accessible to other proteins in the cell. During mitosissome of the chromatin-remodeling complexes are inactivated Another way of altering chromatin structure relies on the reversible chemical modification of the histones. The tails of all four of the core histones are particularly subject to these covalent modifications.
For example, acetyl, phosphate, or methyl groups can
be added to and removed from the assembled nucleosome by enzymes that reside in the nucleus. These modifications of the histone tails have little direct effect on the stability of an individual nucleosome. But some seem to directly affect the stability of the 30-nm chromatin fiber and the higher-order structures. Different patterns of histone tail modifications attract different proteins, some of which cause further condensation of the chromatin, whereas others facilitate access to the DNA by decondensing chromatin. Like the chromatin-remodeling complexes, the enzymes that modify histone tails are tightly regulated. The histonemodifying enzymes work in concert with the chromatinremodeling complexes to condense or decondense stretches of chromatin, allowing local chromatin structure to change rapidly according to the needs of the cell.
ATP-dependent chromatin remodeling complex
Fig. Chromatin-remodeling complexes
reposition the DNA wrapped around nucleosomes.
Interphase chromosomes contain both condensed
and more extended forms of chromatin
The chromatin in these chromosomes is not
uniformly packed. Regions of the chromosome that contain genes that are being expressed are generally more extended, while those that contain quiescent genes are more compact. The most highly condensed form of interphase chromatin is called heterochromatinmakes up about 10% of an interphase chromosome. The formation of the most common form of heterochromatin is induced by a particular set of histone tail modifications, including the methylation of lysine residue 9 in histone H3.
These modifications attract a set of
heterochromatin-specific proteins, which then induce the same histone tail modifications in adjacent nucleosomes. The new tail modifications in turn recruit the same set of heterochromatin-specific proteins, causing a spreading wave of condensed chromatin to propagate along the chromosome. In this manner, an extended region of heterochromatin is established along the DNA. Most DNA that is permanently folded into heterochromatin in the cell does not contain genes. Because heterochromatin is so compact, genes that accidentally become packaged into heterochromatin usually fail to be expressed.
Such inappropriate packaging of genes in heterochromatin can
cause disease: in humans, the gene that encodes -globin which forms part of the oxygen-carrying hemoglobin molecule is situated next to a region of condensed chromatin. If, because of an inherited DNA deletion, that region of heterochromatin spreads, the -globin gene is poorly expressed and the person develops a severe form of anemia. Perhaps the most striking example of the use of heterochromatin to keep genes shut down, or silenced, is found in the interphase X chromosomes of female mammals. Female cells contain two X chromosomes, where male cells contain one X and one Y. Because a double dose of X-chromosome. products would be lethal, female mammals have evolved a means of permanently inactivating one of the two X chromosomes in each cell. At random, one or other of the two X chromosomes in each cell becomes highly condensed into heterochromatin early in embryonic development. Thereafter, the condensed and inactive state of that X chromosome is inherited in all of the many descendants of those cells.
The rest of the interphase chromatin
is called euchromatin. Although the term is used to refer to chromatin that exists in a more extended state than heterochromatin, it is now clear that both euchromatin and heterochromatin are composed of mixtures of different chromatin structures, each established and maintained by different sets of histone tail modifications that attract distinct sets of non-histone proteins
Changes in chromatin structure can
be inherited When a cell replicates its genome, each daughter DNA helix receives half of its parents histone proteins. With those histone proteins come the covalent modifications associated with the type of chromatin structure that was present in each particular region of that parental chromosome. Thus, each daughter chromosome will initially contain an intermixed set of two types of nucleosomes: those that contain the modified histones inherited from its parent chromosome, and those that contain newly synthesized histones, which have not yet been modified. At this point, proteins that recognize the modified histones may bind to the parental histones and deposit the same type of modification on the nearby virgin histones, re-establishing the pattern of chromatin structure found in the parent
The ability to inherit localized chromatin
structure helps eucaryotic cells to remember whether a gene was active in its parental cell, a process that appears to be critical for the establishment and maintenance of different cell types, tissues, and organs during the development and growth of a complex multicellular organism. This type of inheritance does not involve passing along specific DNA sequences from one cell generation to the next, but instead depends on passing along specifically modified histone proteins. It is an example of epigenetic inheritance.