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Using Genomic Databases
Introduction:
An organism’s genome is the complete set of DNA contained within the haploid set of
chromosomes found in the gametes and includes all of the genes that are needed to make and
maintain them as a complex living organism. In eukaryotes, a copy of the organism’s genome
is contained within each of their cells, provided that cell has a nucleus to house the DNA.
The size of an organism’s genome depends on its species. The human genome, for instance, is
more than three billion base pairs in length, while the fruit fly (Drosophila melanogaster) has a
much smaller genome of approximately 165 million base pairs in length. However, size isn’t the
only way in which we can compare and contrast the genomics of different species. For instance,
we can also look at the level of similarity between different gene sequences. Overall, the more
differences that exist between the genomes of different organisms, the less related the two
organisms are likely to be.
Modelling is an important type of scientific methodology that is often used in comparative
genomics to observe these genomic differences. Thanks to the work of the Human Genome
Project (HGP) and the genetic data that it has generated, we as researchers are now able
to use extensive databases to model the genetic similarities between species. This can be
done to a very high resolution using comparative software programs that analyse genomic
sequences across different organisms. In this investigation, you will be using a free online
software program to compare a particular gene sequence in humans with that of the mouse,
chimp, and cow. Specifically, you will look at a gene called TYR, which is responsible for the
production of the enzyme tyrosinase.
Aim:
To observe the genomic similarities between four species for the TYR gene using the comparative genomics program VISTA.
Website Link : pipeline.lbl.gov/cgi-bin/gateway2
Method:
1. Visit the following website: pipeline.lbl.gov/cgi-bin/gateway2
2. Change position reference to: chr11: 89,177,565 – 89,295,759 (as pictured above) This refers to the specific molecular location of the TYR gene, which is located on the human chromosome 11 between base pairs 89 177 565 and 89 295 759.
3. Click submit and you will be redirected to this page, which shows genomic alignment between the human TYR gene and the equivalent sequence in a mouse genome (as pictured in figure 2 below).
4. It is now time to add more species into your alignment model. This can be done by adding alignments in the top right of your drop down menu (as pictured in figure 3 below). For this model, let’s add both a chimp and a cow genome into our comparison.
5 Once your model is complete with the gene sequences of the mouse, chimp, and cow, it is now possible to compare the similarities between the four species at this specific gene locus. For this exercise we will look at two specific points of comparison:
a. the visual graph data (Figure 4)
b. the molecular location (Figure 5)
RESULTS
Fill in Table 1 using the results of your investigation to list the species from most similar to least similar to humans at this locus.
Using the results from Figure 5, which show the molecular locations of this gene across each species, complete Table 2.
DISCUSSION QUESTIONS
1. Describe the Human Genome Project (HGP) and why it was important for the field of comparative genomics.
2. Referring to your results, summarise the findings of this investigation.
3. Using the alignment details (shown in Figure 5), identify the length and location of the corresponding gene region in the cow genome.
4. Discuss whether this type of investigation is repeatable, reproducible, and valid. Why or why not?
5. Identify an advantage of using a model in this case.
6. Using visuals and diagrams are an important part of scientific communication. Compare and contrast the role of Figure 4 and Figure 5 in this investigation.
7. Transforming data is another important part of scientific communication. How else could you represent the data shown in Figure 4?
CONCLUSION
Summarise the findings of this investigation. Be sure to:
• address the aim of the investigation
• comment on the genomic similarities between the species
• identify any limitations in this investigation and suggest potential improvements.
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