Chromosome loops

FIGURE 12.31 A model for chromosome structure, human chromosome 4. The 2-um DNA helix is wound twice around histone octamers to form 10-um uucleosomes, each of which contains 160 bp (80 per turn). These uucleosomes are then wound in solenoid fashion with six uucleosomes per turn to form a 30-nm filament. In this model, the 30-nm filament forms long DNA loops, each containing about 60,000 bp, which are attached at their base to the nuclear matrix. Eighteen of these loops are then wound radially around the circumference of a single turn to form a miniband unit of a chromosome. Approximately 10 of these minibands occur in each chromatid of human chromosome 4 at mitosis. 

Step 5 Loop through each bit of each chromosome in the population and perforin genetic mutation i.c. flip the bit-value (0 1 and 1 0) at each locus with some (typically small see below) probability, p,j. (In practice, this step is combined with step 4.)... 

Finally, we mutate each bit of the resulting chromosomes with some small probability - say Pm = 0.05. In our example we find that values of the fifth bit in C4 and sixth bit in C5 are flipped. The resulting strings make up our 2" generation chromosome population. By chance, the first loop through the algorithm has successfully turned up the most-fit chromosome - C4 =(111111)—> /(C4) = 63 = 3969 - but in general the entire procedure would have to be repeated many times to approach the desired solution. 

The eytoplasm is a viscous fluid and contains within it systems of paramount importance. These are the nucleus, responsible for the genehc make-up of the cell, and the ribosomes, whieh are the site of protein synthesis, hi addihon are found granules of reserve material suehas polylydioxybutyric add, an energy reserve, and polyphosphate or volutin granules, the exact funchon of which has not yet been elucidated. The prokaiyohc nueleus or bacterial chromosome exists in the cytoplasm in the form of a loop and is not surrounded by a nuclear membrane. Bacteria cany other chromosomal elements episomes, which are portions of the main chromosome that have become isolated firm it, and plasmids, whieh may be called miniature chromosomes. These are small annular pieees of DNA whieh carry a limited amount of genetic information. 

The primary Junction of the nucleosomes is to condense DNA. Further condensation of nucleosome DNA requires nonhistone nuclear proteins. These proteins make up a scaffoldlike structure around an additional helix consisting of coiled nucleosomes. This produces a structure that resembles a solenoid, with six nucleosome subunits per turn. The solenoid structure can form large loops that give additional structure to the incipient chromosome. 

Figure 1. Hierarchical model of chromosome structure, (a) In interphase cells, DNA is packed in a nucleus as forming nucleosome and chromatin, (b) DNA forms nucleosome structure together with core histone octamer, which is then folded up into 30nm fiber with a help of linker histone HI. This 30 nm fiber is further folded into 80 nm fiber and 300 nm loop structures in a nucleus. In mitosis, chromosome is highly condensed. Proteins which are involved in each folding step are indicated above and non-protein factors are indicated below, (c) The amino acid sequences of histone tails (H2A, H2B, H3 and H4) are shown to indicate acetylation, methylation and phosphorylation sites. (See Colour Plate 1.)...

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Two histone molecules each of types H2A (blue), H2B (green), H3 (yellow), and H4 (red) form an octameric complex, around which 146 bp of DNA are wound in 1.8 turns. These particles, with a diameter of 7 nm, are referred to as nucleosomes. Another histone (HI) binds to DNA segments that are not directly in contact with the histone octamers ( linker DNA). It covers about 20 bp and supports the formation of spirally wound superstructures with diameters of 30 nm, known as solenoids. When chromatin condenses into chromosomes, the solenoids form loops about 200 nm long, which already contain about 80 000 bp. The loops are bound to a protein framework (the nuclear scaffolding), which in turn organizes some 20 loops to form minibands. A large number of stacked minibands finally produces a chromosome. In the chromosome, the DNA is so densely packed that the smallest human chromosome already contains more than 50 million bp. 

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