It is important for conditions such as Parkinson's to be studied in mice because it allows us to study the mechanism of the disease and test possible treatments in a timely manner without risking human life. In the scientific world, mice are considered model organisms because they are more prolific than humans and it is easier to follow inheritance through generations in mice than it is in humans because mice have a shorter generation time than humans. Mice also have a comparable genome to humans, so they are exemplary in many cases to see how gene manipulation in mice will affect humans. Also, when using mice in a lab, it is much easier and more ethical at this time to extract genes and manipulate the genomes of the mice.
2. Name five non-human taxa that are included in the results of the BLAST. What does this tell you about the Parkin gene?
Although there were many non-human taxa that were included in the results, five specifically mentioned were: Pongo abelii, or the Sumatran orangutan; Macaca fascicularis, the crab-eating macaque; Sus scrofa, the wild boar; Equus caballus, the wild horse; and Mus musculus, the common mouse. Clearly, this tells us that many non-human taxa contain the Parkin gene or a Parkin-gene analog. Because of this, we believe that the mitochondrial health of these organisms depends on the Parkin gene, like we have seen in humans. As is seen in the paper that we reviewed, the Parkin gene works with the PINK1 gene to maintain mitochondrial health and destroy unhealthy mitochondria to prevent a build up of free radicals that signals for neuronal cell apoptosis. In the case of humans, this neuronal apoptosis causes an onset of familial Parkinson’s disease. Because so many taxa have the Parkin gene, it can be helpful for laboratory testing and genetic research to see the effect of gene manipulation and mutation, and how these mutations may have an effect on Parkinson’s disease itself.
In most cases, in non-familial Parkinson’s disease,
it is not subject to natural selection because it does not affect a patient’s
fitness. In the majority of cases, Parkinson’s develops after the
child-bearing years of the patient. In the case of familial Parkinson’s
(discussed in our paper), we believe that this form of Parkinson’s disease can
be subject to natural selection. In the familial form of the disease, it
is possible for patients to develop the disease at a much younger age and pass
the defective Parkin gene to their children. This early-onset Parkinson’s
can indeed have an effect on the fitness of the patient. If the effect on
fitness is extremely detrimental, then natural selection will act on the
disease, and the Parkin gene will be selected against.
4. Refer to the last paragraph of the Results and Discussion (pages 5&6). Discuss selection for and against the defective mitochondria associated with PINK1 mutant cells.
Bonus: What types of mutations are described in the second column of Table 1 (SNPs, substitutions, indels, missense, nonsense, transitions, transversions, etc.)?
Defective mitochondria can be positively selected for in certain
circumstances, which are associated with anaerobic metabolism.
1. If
muscle tissue does not receive enough blood supply to prevent anaerobic
metabolism, it is subject to more stress than in normal circumstances. This
type of environment is more prone to mitochondrial disease, so defective mitochondria
are therefore positively selected for.
2. In
the central nervous system, normal mitochondria are required in order to
convert non-glucose fuel such ketone bodies. This is especially important in
infancy, when the CNS requires more fuel to facilitate growth, or during
periods of fasting, when glucose is not readily available. While normal
mitochondria are converting, defective mitochondria have a replicative
advantage during these times.
3. During
fetal life, anaerobic metabolism maintains relatively low levels of pH and Po2,
which gives defective mitochondria a selective advantage over normal
mitochondria (Clarke, 1990).
Defective mitochondria are
selected for in familial Parkinson’s disease, which we have seen in this paper.
The mutated PINK1 gene impairs normal mitophagy, which gives mutated
mitochondria an advantage, due to a decrease in the removal of defective
mitochondria.
Defective mitochondria can also
be selected against, which has been observed in normal physiology. Normally,
defective mitochondria are selected against during the process in which PINK1
and parkin remove defective mitochondria by mitophagy.
The mutations described in the second column of Table 1 are substitutions. The shorthand on the table is denoting the chromosomal location and then the substitution caused the mutation (ex: C > G, which would denote cytosine to guanine).
