1) Proto-Oncogenes and Tumor Suppressor Genes are two types of genes that ordinarily keep the cell cycle functioning as it should. Explain the roles of these two types of genes, and explain what can occur when these types of gene are not working properly. Provide at least two different examples of cancers associated with mutations of these types of genes.
The purpose of the proto-oncogenes under normal circumstances is to make sure that cells proliferate, in other words the oncogenes stimulate cell production. But when a normal, healthy ocogene cell becomes mutated or expresses at higher than normal levels it causes cancer. The first oncogenic virus was discovered in 1916 and called the Rous virus after the person who discovered it, Peyton Rous. Rous viruses represent a family of viruses called the retro viruses. Retro viruses contain a genetic material called ribonucleic acid (RNA).
There is always the possibility that RNA will be transcribed into DNA (deoxyribonucleic acid) by an enzyme of the rous virus. The enzyme is called reverse transcriptase. An oncogene has dominant behaviour; only one mutant allele can bias the cell towards tumour formation. (An allele contains encoded inheritable information from the parents.)
A Tumour Suppressor Gene is a gene that suppresses mitosis; in other words the formation of two new cells from a eukaryotic cell by mitosis is inhibited. Mitosis is when the eukaryotic cell splits into two cells each of the resulting two cells has a complete gene set, mitochondria, ribosomes, a section of endoplasmic reticulum and other organelles depending on the purpose of the cells. A mutant allele is recessive so the cell is protected from cancer as long as one normal allele is present.
Cancer of the eye retina is caused by a RB (retinoblastoma) gene. The cancer affects newborns with multiple tumours that grow in both eyes of a new baby. Or in a very young child the cancer can stop the retina of one eye from mitosis which causes retina growth to stop. The first type of RB is inherited from a mutated chromosome of one of the parents. Normally the Rb protein controls the cell cycle so that the mechanisms work well. A signal or message reaches the Rb protein to complete the development from JG1 to mitosis is initiated at the appropriate time.
Heterozygosity refers to cells with one normal and one mutated gene, but they are normal because tumour suppressor genes recessive. LOH (Loss of Heterozygosity) is when the ability to act as a tumor suppressor is lost. In men who have one X chromosome but no Y chromosome tumors can start growing when WTX is damaged or deleted. (WTX is an x-linked tumour suppressor gene.) In women if the X chromosome has not been inactivated then mutation or deletion of the WTX can allow tumours to start growing.
2) Explain the structure of the DNA double helix, including its subunits and the way in which they are bonded together.
A DNA is a deoxyribonucleotide polymer and its purpose is to store genetic data. The shape of DNA is a double helix because two strands of polynucleotide wind around each other to form the shape. Each of the strands has a backbone made of deoxyribose and phosphate groups. The phosphate group is a phosphorus molecule with three of the oxygen molecules attached to the phosphorus by single bonds and one oxygen attached with double bonds. New strands are made from deoxynucleoside triphosphates. Pentose is the carbon ring which contains 4 carbons and one oxygen. When a phosphate group is bonded to the 5th carbon atom of a dexoyribose strand then it is covalently bonded to the 3rd carbon of the next deoxyribose strand. At the same time DNA strands are constructed in the 5’ to 3’ direction. Nucleotides form covalent links with the free 3’ carbon atom on the pentose ring. At the same time the 2nd and 3rd phosphates separate from the structure as one molecule of pyrophosphate (PPi). The strand is the template where the nucleotides are placed in the correct order depending on the order of the bases; each C guides G insertion on a new strand, and then G guides C insertion and the same two steps are repeated continues form there until the structure of two molecules being formed from the parent molecule are complete.
The two template strands (5’, 3’) form a replication fork. That is the point where the formation of the new DNA begins with two strands replicating the steps necessary to form DNA begins. The two strands used to build the new structure are configured anti-parallel to their parent; the leading strand (5’) the other is the lagging strand (3’).
3) Gregor Mendel is known as the Father of Genetics based on his research with pea plants in the 19th Century. Explain the Law of Segregation and the Law of Independent Assortment and explain how this applies to Darwin’s Theory of Natural Selection. Provide examples from in-class labs, as well as outside resources.
Mendel observed how gene variants are segregated (or separated) into cells that are in charge of reproduction. He studied the reproductive cells of heterozygous pea plants. The Law of Segregation is the fundamental principle that he observed – when two of the plants were crossed the offspring did not necessarily have matching traits to the parent plants. He surmised that the alleles which hold encoding traits from the parent plants had become segregated during the reproduction cells development. Modern research found that the gene segregation occurs in the eukaryote cells during meiosis. Meiosis is the phase of the cell cycle when gametes are produced. Gametes are the four reproductive cells produced from the fifty percent reduction of chromosomes in a parent cell.
The Law of Independent Assortment is a principle Mendel formulated when he was experimenting with hybrid crosses. A hybrid cross is when two organisms used for reproduction vary from each other by two traits. His data from the experiment showed that the reproduced offspring did not necessarily inherit the same trait combinations that were exhibited in the parents. In modern biology that it has been shown that independent assortment of genes takes place in the eukaryote cell during meiosis, the same phase during which segregation occurs. Meiosis in humans means that the 46 chromosomes of each parent is halved to 23 chromosomes each; each set of 23 traits are inherited by the offspring. When pairs of chromosomes are similar they are called homologous chromosomes. Haploid cells are the homologous cells after they have been halved but the new assortment of haploid cells from the division has been produced randomly. In other words a random mixture of the father’s and the mother’s genes are available after meiosis, the traits therefore have been randomly chosen.
The second feature of The Law of Independent Assortment is recombination which occurs during meiosis. The recombination causes new gene combination to be formed from the pieces of DNA available during meiosis. The genes of the male and female parents are mixed and so the genes of the new baby to be born are assorted independently one from the other. Therefore the cells are formulating a new combination of features so the new baby (in humans) will be unique. Although, if there are genes in close proximity to one another on a chromosome, then genetic linkage does not allow the genes to be independent.
References
Kimball, J. W. Biology 5th Ed., Boston: Addison-Wesley, 1983.
Voet, D. and Voet J.G. Biochemistry 4th Ed., NY: John Wiley and Sons, 2011.
