Gene and Chromosome Mutation.

Unlike, euploidy, aneuploidy is when changes occur that affect only parts of the chromosome set. There are several examples of how this may arise. If a part of the chromosome becomes deleted completely then this can lead to the loss of important genes. Inversions occur when a region of DNA breaks off from the chromosome and re-attaches itself, however with a flipped orientation with respect to the rest of the chromosome. Sometimes chromosomes can lose track of where they are meant to go in cell division. One of the daughter cells will end up with more or less than its share of DNA. This is called chromosome nondisjunction. When large regions of a chromosome are altered, it may lose the ability to segregate properly during cell division causing a chromosome nondisjunction. When a new cell gets less or more of its share of DNA, it will have problems with gene dosage. Expression of genes is specifically tailored to a level that a cell requires. Another case may be where a part gets broken off and added to a different chromosome or even duplications of parts. Aneuploidy in humans has serious consequences. For example if there is an extra chromosome 21 present so that each cell has 47 chromosomes in the nucleus then the person is affected with Down's syndrome. They have some degree of learning difficulty, retarded physical development and a distinctive body and facial structure. The cause of the duplication of a single chromosome is not known. Examples of aneuploids involving sex chromosomes include:

XO - Turner's syndrome produces a sexually underdeveloped and sterile female.

XXY or XXXY - Klinefelter's syndrome produces a sterile male with marked female features.

XYY - a normal male but socially deviant with a propensity for violence.

> Gene Mutations

A gene is a sequence of nucleotide pairs which codes for a sequence of amino acids. Gene mutations occur on a smaller scale to chromosome mutations because they can occur to any base pair of any gene, anywhere along a chromosome. The coding length of a gene is typically 1200 to 1500 base pairs long. A change in one or more base pairs can cause a mutation which shows exactly how easy it is for this to occur.

Sometimes the enzyme machinery occasionally inserts a base other than that coded by the template DNA. Alternatively, gene mutations may be induced by particular conditions affecting the cells. The environmental agents (mutagens) include ionising radiation in the form of X-rays, cosmic rays and ?-, ?- or ?-radiation from radioactive isotopes. The rate of mutation induced by these mutagens is directly proportional to the dose received. Their effects are also cumulative so small doses over a prolonged period may be as harmful as a single larger dose. Only replicational errors occurring at meiosis can affect gametes and offspring. Non-ionising mutagens include ultra-violet light and numerous chemicals.

Point mutations are single base pair changes. A nonsense mutation creates a stop codon where none previously existed. This shortens the resulting protein, possibly removing essential regions. A missense mutation changes the code of the mRNA. E.g. If an AGU is changed to an AGA the protein will have an argenine where a serine was meant to go. This might alter the shape or properties of the protein. A silent mutation has no effect on protein sequence. E.g. if AGU was changed to AGC the protein would still have the appropriate serine at that point. Silent mutations occur because of built in buffers in the system. Since there are three bases coding for each amino acid, there are over 60 combinations possible but there are only around 20 amino acids existing. So some triplet codes account for the same amino acid and this is, although small, a good buffer against gene mutations.

Within a gene small insertions or deletions of a number of bases not divisible by three will result in a frame shift. The frame shift may move along the functional code so that anything after it because misplaced and dysfunctional or the frame shift might even generate a stop codon thus prematurely ending the protein.

The effects of mutations are only occasionally beneficial because after all a mutation is a random change in an established protein structure. In fact, many mutations are lethal, or at least disadvantageous. Most mutations are recessive to the normal allele so for a beneficial mutation to become present, it awaits many generations in the gene pool before chance brings the recessive alleles together.

If replication of DNA proceeded as was described previously, the DNA polymerase wouold make a mistake on average about every 1000 base pairs. This level would be unacceptable, because too many genes would be rendered non-functional. Organisms have elaborate DNA proofreading and repair mechanisms, which can recognize false base-pairing and DNA damage, and repair it. The actual error rate is more in the region of one in a million to one in a billion.