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Breast Cancer Gene Comparison Across Species
Zappacosta J, Jenne M, Test S
The Richard Stockton College of New Jersey
Abstract
Breast cancer is becoming more and more prevalent in society, and the BRCA1
gene is integral to understanding how it works. A study of BRCA1 protein and
nucleotide sequences was performed using nine species. Each species had similar
BRCA1 sequences, which highlighted the lineage of the gene from the beginning of
evolutionary history. According to the rooted phylogenic trees that compared the
BRCA1 protein and nucleotide sequences, it was clear that the most closely related
species had the most similar BRCA1 genes. As a result of this information, further
studies into the functionality of BRCA1 can be done on any species. If information is
gained about the gene, its function, and its variants/mutations in any species, it is likely
to carry over to humans as well. This, of course, should be confirmed on a case by
case basis, but it is important information nonetheless.
Results
Conclusion
As can be seen in figures 1 and 2, alignments of both the nucleotide and protein
sequences of BRCA1 follow closely with speciation. In other words, those species that
are most closely related phylogenetically are closest together on the trees. Similar
information is shown on Table 1, which uses percentages to show how similar BRCA1 is
for each pair of species. These three figures strongly imply that the BRCA1 gene came
about early in the evolution of animals, and that it has diverged slowly over time. This is
further supported by alignments of the species used, in which it can be seen that the
differences between the species come mostly from gaps in the BRCA1 gene. All of these
observations together imply that the functionality of BRCA1 is similar for all animal
species and that the functional sites on the gene should be the same/similar for each.
As can clearly be seen in this study, conservation of
BRCA1 sequences is strongly correlated with evolutionary
speciation. In other words, species with more similar
BRCA1 sequences tend to be more closely related. This
implies that the BRCA1 gene came about early in
evolutionary history, and that its function is extremely similar
among all animal species.
As a result of this information, further studies into the
functionality of BRCA1 can be done on any species. If
information is gained about the gene, its function, and its
variants/mutations in any species, it is likely to carry over to
humans as well. This, of course, should be confirmed on a
case by case basis, but it is important information
nonetheless.
Introduction
Five to ten percent of all breast cancer patients in both men and women have been
experimentally attributed to malfunctions in the tumor suppressor genes, BRCA1 and
BRCA2. When a BRCA1 or BRCA2 mutation is inherited by a person, the risk of
contracting breast cancer or ovarian cancer increases dramatically to over eighty percent.
An inherited mutation in BRCA1 ultimately changes the function of the gene from a tumor
suppressor to an abnormal growth regulator. BRCA1 can have protein mutations
anywhere along its DNA sequence but has a higher chance to become malignant or
cancerous if mutated on the 5’ end of the sequence. Since the mutations that occur on the
5’ end have a greater chance to develop cancer, the 5’ end of the sequence has been
targeted as more important to normal/abnormal protein function.
The BRCA1 gene is also found in most animals, and thus can be compared to the
human BRCA1 gene sequence to help draw meaningful conclusions on functionality. By
running comparative analyses on a number of different species, the DNA sequences that
contribute to normal and abnormal functionality can be discerned. The species that will be
used are Homo sapiens, Bos Taurus (bovine), Canis familiaris (dog), Gorilla gorilla gorilla,
Pan troglodytes (chimpanzee), Macaca mulatta (rhesus macaque), Mus musculus
(mouse), Pongo pygmaeus (bornean orangutan), and Rattus norvegivus (rat). By using
this wide array of species, it should be possible to isolate the sections of BRCA1 that are
most important to its functions, which allows for greater risk assessment in individuals with
inherited mutations.
It has been hypothesized that tumor suppression functionality is contained mostly in the
BRCT domains at the C-terminus of the protein and the N-terminal ring domain. If this is
actually the case, then the comparative analysis should show highly conserved sequences
in those regions.
Methods
1. University of Washington comparative study (Szabo et al. 1996) obtained as a basis
for further investigation.
2. The Expasy-Prosite database was used to obtain nucleotide sequences and to
decide on which species would be appropriate to use. It linked to the Uniprot
database.
3. Uniprot was used to find animal species with verified BRCA1 nucleotide sequences.
Nine were chosen and the sequences gathered in FASTA format.
4. The National Center for Biotechnology Information’s protein database (ncbi) was
used to gather the BRCA1 protein sequences for the same nine species.
5. Using the SDSC Biology Workbench tool, rooted and unrooted comparative trees
were generated for both the protein sequences and the nucleotide sequences (total
of four trees) using ClustalW alignment. Only the two rooted trees were used in
order to increase clarity.
6. The Biology Workbench tool was also used to align the nucleotide sequences to
obtain the comparative percentages between each of the species.
7. The alignments above were observed to determine what the differences were in
general.
Figure 1
BRCA1 Protein Rooted Tree
Norway Rat (Rattus norvegicus)
Figure 2
House Mouse (Mus musculus)
Dog (Canis lupus familiaris)
BRCA1 DNA Rooted Tree
Cattle (Bos taurus)
Norway Rat (Rattus norvegicus)
Rhesus Monkey (Macaca mulatta)
House Mouse (Mus musculus)
Dog (Canis lupus familiaris)
Orangutan (Pongo pygmaeus)
Cattle (Bos taurus)
Human (Homo sapiens)
Rhesus Monkey (Macaca mulatta)
Chimpanzee (Pan troglodytes)
Gorilla (Gorilla gorilla)
Orangutan (Pongo pygmaeus)
Human (Homo sapiens)
Chimpanzee (Pan troglodytes)
Table 1
Gorilla (Gorilla gorilla)
Similarity Percentages of BRCA1
Nucleotide Sequences
Human
Human //////////////
Norway Rat
Orangutan
House Mouse
Rhesus Monkey
Chimpanzee
Western Gorilla
Dog
Cattle
72.9
98.3
72.6
96
99.3
99.1
83.3
82.6
Norway Rat Orangutan House Mouse Rhesus Monkey Chimpanzee Western Gorilla
Dog
Cattle
72.9
98.3
72.6
96
99.3
99.1
83.3
82.6
////////////// 72.9
88
72.9
73
72.8
70.9
70.3
72.9 ////////////// 72.6
96.1
98.5
98.4
83.3
82.4
88
72.6 ////////////// 72.7
72.8
72.5
70.1
70
72.9
96.1
72.7 ////////////// 96.2
96
83.1
82.2
73
98.5
72.8
96.2 ////////////// 98.4
83.4
82.6
72.8
98.4
72.5
96
98.4 ////////////// 83.3
82.5
70.9
83.3
70.1
83.1
83.4
83.3 ////////////// 81.8
70.3
82.4
70
82.2
82.6
82.5
81.8 //////////////
References
1. Apweiler R, Bairoch A, Wu C. 2004. Protein sequence databases. Curr Opin Chem Biol 8(1):
76-80
2. - Artimo P, Jonnalagedda M, Arnold K, Baratin D, Csardi G, de Castro E, Duvaud S, Flegel V,
Fortier A, Gasteiger E, Grosdidier A, Hernandez C, Ioannidis V, Kuznetsov D, Liechti R, Moretti
S, Mostaguir K, Redaschi N, Rossier G, Xenarios I, and Stockinger H. ExPASy: SIB
bioinformatics resource portal, Nucleic Acids Res, 40(W1):W597-W603, 2012.
3. National Center for Biotechnology Information [Internet. Bethesda (MD):U.S. National Library of
Medicine [cited 2014 April 23]. Available from: http://www.ncbi.nlm.nih.gov/
4. San Diego SuperComputer Center [Internet]. 2012. LaJolla(CA):The regents of the University
of California [cited 2014 April 23]. Available from: http://www.sdsc.edu/
5. Silver DP, Livingston DM. 2012. Mechanisms of BRCA1 Tumor Suppression. Cancer Discovery
2:679-684.
6. Szabo CI, Wagner LA, Francisco LV, Roach JC, Argonza R, King MC, Ostrander EA. 1996.
Human, canine and murine BRCA1 genes: sequence comparison among species. Hum Mol
Genet 5(9):1289-1298.