DNA is packaged in chromosomes

Each human chromosome contains one very long DNA molecule which unravelled would measure about 4.8 cm in length. The total length of DNA in the nucleus of a human cell has been estimated to be about 2.2 m. This poses a packaging problem: how does a chromosome measuring оn average 6 µm long contain about 8000 times its length of DNA? The answer is that chromosomal DNA is intricately folded and is tightly bound to protein molecules called histones. Histones are small proteins that are rich in the amino acids lysine and/or arginine.

The complex formed between DNA and histones is called chromatin. Chromatin takes up stain and is visible in non-dividing nuclei. Individual chromosomes can be seen under the light microscope only during cell division (mitosis or meiosis).

Nucleosomes - the basic structural unit

Each DNA molecule is wound around histones arranged in groups of eight known as octamers.

The DNA and octamers form bead-like structures known as nucleosomes. Positively charged groups on the side-chains of the histones form strong ionic bonds with negatively charged phosphate groups in the backbone of the DNA.

In each nucleosome, a length of DNA containing about 150 base pairs is wrapped around the octamer.

Another histone molecule attached to the outside of the nucleosome binds DNA to the octamer.

The nucleosome is regarded as the basic unit of the structure. The linker region, the stretch of DNA between the nucleosomes, varies in length from 14 to over 100 base pairs.

Nucleosomes fold to form solenoid fibres

More histones in the linker region help to fold the thread of DNA and nucleosomes (the nucleosome fibre) into a tightly coiled structure called a solenoid. The solenoids are thought to be further looped and coiled around non-histone proteins called scaffolding proteins. The precise details of this higher level of folding are not known.

The centromere

Each chromosome has acentromere which usually appears as a constriction when the chromosomes condense during mitosis and meiosis. The position of the centromere can be used to distinguish between different chromosomes.

Centromeres do not contain any genes. However they do contain large segments of highly repetitive DNA, called alpha satellite DNA. This is thought to play a significant role in centromere function. The centromere contains the kinetochore. This is a densely staining structure that attaches the chromosome to the spindle apparatus during nuclear division. Centromeres control the distribution of chromosomes during cell division. Chromosomes that do not have centromeres cannot divide.

Telomeres

Telomeres are located at the ends of chromosomes. They consist of DNA and protein. The telomeres appear to play a vital role in maintaining the stability of the chromosomes, 'sealing' the ends of linear DNA. They have been likened to the tips of shoelaces, and have a similar function: to stop the DNA fraying. They also seem to play an important role in regulating cell division. Under normal circumstances, telomeres become shorter and shorter with each cell division. When the telomeres have shortened to a certain critical length, the cell stops dividing.

If the telomeres are removed, the chromosome disintegrates. It is thought that the ageing process may be linked to telomere damage.

Telomeres: a role in cancer?

Telomeres contain repeating sequences of bases which are synthesised with the help of an RNA-containing enzyme called telomerase. Telomerase activity is suppressed in normal human somatic (body) cells. However, in cancerous cells, telomerase is active and maintains the telomere length so that the cells continue to divide. It is thought that this abnormal retention of the telomeres is involved in the development of some types of cancer.

Variation

 

The Earth is inhabited by billions of organisms, every one of which is unique. Individuals belonging to different species are usually easy to distinguish; members of the same species may differ only in small ways; but even clones (such as identical twins) show some subtle differences. The differences between individuals of the same species are called variation.These differences may be the result of genetic differences, the influence of the environment, or a combination of genetic and environmental influences.

Genetic variation

Genetic differences reflect the genotypeof an organism, that is, its genetic make-up. A diploid organism has two sets of chromosomes and two forms (alleles)of each particular gene. These alleles may be the same (the organism is homozygous for that gene) or different (the organism is heterozygousfor that gene). If different, one of the alleles (the dominant allele)may mask the other allele (the recessive allele).The dominant allele is therefore expressed in either the heterozygous or the homozygous condition, whereas the recessive allele is expressed only in the homozygous condition. If an organism is haploid (that is, it has only one set of chromosomes), all its alleles will be expressed and will be reflected in its observable or measurable characters(the features or traits transmitted from parent to offspring).

Phenotypic variation: continuous and discontinuous

The measurable physical and biochemical characteristics of an organism, whether observable or not, make up its phenotype.The phenotype results from the interaction of the genotype and the environment. The genotype determines the potential of an organism, whereas the environmental factors to which it is exposed determine to what extent this potential is fulfilled. For example, in humans the potential height of a person is genetically determined, but a person cannot reach this height without an adequate diet. Phenotypic variation (commonly referred to simply as variation) is of two main types: continuous and discontinuous.

In continuous variation,differences are slight and grade into each other. Characteristics such as human height and weight show continuous variation, and are usually determined by a large number of genes (they are polygenic)and/or considerable environmental influence.

In discontinuous variation,the differences are discrete (separate) and clear cut: they do not merge into each other. Discontinuous variations are generally caused by different alleles of one, two, or only a few genes.

Continuous variations are usually quantitative (they can be measured) whereas discontinuous variations are qualitative (they tend to be defined subjectively in descriptive terms). Thus height in humans is a continuous variation given a value in metres, whereas height in sweet peas is a discontinuous variation described as 'tall' or 'dwarf.

Mutations: more variation

Genetic variation arises partly from sexual reproduction by a combination of independent assortment, crossing over, and random fertilisation. However, these processes merely shuffle the existing pack of genes so that new combinations are made. The ultimate source of inherited variations is mutations.

A mutationis a change in the amount or the chemical structure of DNA. If the information contained within the mutated DNA is expressed (that is, transcribed into mRNA and translated into a specific polypeptide chain) it can cause a change in the characteristics of an individual cell or an organism. Mutations in the gametes of multicellular organisms can be inherited by offspring. Mutations of the body cells of multicellular organisms (somatic mutations) are confined to the body cells derived from the mutated cell; they are not inherited.

Mutations can happen spontaneously as a result of errors in DNA replication or errors during cell division, or they can be induced by various environmental factors (such as certain chemicals, X-rays, and viral infection). Factors that induce mutations are called mutagens.








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