Biology 1002B Study Guide - Midterm Guide: Tumor Suppressor Gene, Feline Leukemia Virus, Gene Duplication
Biology 1200b – Test Three
Lecture 18 – Cancer
In Canada, cancer is the leading cause of non-accidental death. Men are at a higher risk than women.
The top four most common are prostate, breast, lung and colon cancer. Heritability estimates from twin
studies show that there is a rather low correlation (about 0.27-0.42).
Embryogenesis involves rapidly diving cells. The cell cycle involves a complex called CDK (cyclin
dependant kinase) which is a checkpoint that ensures damaged cells do not replicate their DNA. Cyclins
are produced early in the cell cycle where they bond with CDK, which then phosphorylates targets
downstream and releases the G1 checkpoint. Different sets of cyclins are used for each checkpoint.
Expression of proto-oncogenes like EGF promotes cell cycling, which are sometimes treated as the cause
of cancer. They are, however, genes that are required for cell division but may play a role in the rapid-
cell division involved in cancer. The regulation of cell division can be caused by many different genes and
proteins that are involved in the translation of signals from the EGF.
Expression of tumor suppressor genes slow cell cycling. TP53 is a master tumour suppressor gene that
codes a transcription factor whose activity can result in increased DNA repair, cell cycle arrest by
blocking cyclin/CDK and apoptosis (cell death).
Sporadic cancer requires loss of function mutations in both alleles that code for regular cell
development. This is very rare as it involves both alleles to mutate. It is more common through
inheritance since one damaged repressor may be from either parent.
Inappropriate expression of miRNA can promote cycling, for example oncomirs. Different kinds of
tumors have different kinds of miRNA expression and this is diagnostic.
Cancer is deregulation. Uncontrolled growth can arise from upsetting the balance between the activities
of gene products that promote cell cycling versus those products that suppress cell cycling. Cancer is
also progressive. Various steps have to happen for cancer to be expressed.
Cancer may begin as alterations to gene expression in stem cells. Most tissues contain stem cells, which
are called pluripotent. These cells can differentiate into many different types. When a stem cell divides it
creates one differentiated cell and one stem cell. Cells are not the same in tumors. Some are
proliferative and some are not.
A mouse family with high risk for brain tumor has one defective tumor suppressor. A nucleus is removed
from a mouse embryo and replaced with a tumor nucleus and then given an electric shock. The cell then
divides under the control of a tumor nucleus and creates a mouse. Thus the maternal egg reprograms
the tumor nucleus. This means cancer is perhaps epigenetic.
Is cancer contagious? Feline leukemia virus, mouse mammary tumor virus and HPV (human
papillomavirus) are contagious. HPV leads to cervical cancer. It is a DNA virus and many different strains
cause increased growth in different tissues in men and women. The number of new partners greatly
increases chance of acquiring the HPV virus.
Lecture 19 – Molecular Homology
Molecular evolution is the study of evolution at the level of nucleic acid and amino acid. Gene evolution
is the study of how genes change over time. Changes in genes that lead to evolutionary change can be
mutation (insertion, deletion, frameshift), duplication, rearrangement and loss. All of these change
phenotype if they’re going to have an evolutionary effect. Some mutations do not change phenotype.
We will ask the question “how a mutation to a gene causes an enzyme to change substrate specificity”.
Change in phenotype leads to selection.
Homology has many definitions. In this course it means common ancestry. For example, the structure of
a flipper and wing come from a common ancestor and are thus homologous, even though they are not
completely similar. How do we know that they share a common ancestor? The gene GlsA in Volvox and
Chlamy is homologous, but they do not have the same nucleotide sequence, amino acid sequence,
length or function.
Genome annotation involves attaching biological meaning to a sequence of DNA. This results in gene
prediction, detection of regulatory elements, finding biological functions through similarity searches and
can be done automatically using algorithms.
Protein-coding gene prediction is used to detect what protein a gene codes for. There is a computer
algorithm that can be used to detect promoter elements, intron/exon boundaries and other conserved
DNA motifs. The computer sequence can splice out exons to create a deduced protein coding sequence.
Protein prediction involves translating all possible reading frames of the gene and detecting which is the
longest with few stops and starts.
Chlamydomonas has 15,000 predicted proteins. These are not definite but are likely. More work is then
done on the predicted proteins. Similar sequences are then researched. The National Center for
Biotechnology Information contains a Genbank with a sequence database. About 23,500 total genomes
have been fully mapped out.
Sequences can be arranged to show regions of similarity and thus used to detect functional and
structural similarity as well as evolutionary relatedness. There are different kinds of alignments. Global
alignment involves precise similarity between two sequences. Local alignment doesn’t force two
sequences to align perfectly but rather looks for different regions of high similarity.
There are 155 gene sequences at GlsA that are very similar to the Chlamy gene. The Volvox gene is
extremely similar, but there are others that have some similarity to certain parts of the sequence. BLAST
analysis shows that there are differences in the nucleotide alignments and amino acid alignments
between Chlamy and Volvox, and thus neither of these are the definition of homology. They also do not
have the same length or even function.
Amino acid sequence comparisons are more informative than nucleotide.
1. Nucleotides are a four letter alphabet and when converted into bits each base has two bits on
information (A00, G01, C10, T11). If I is the total information in a message with G symbols written in an