GENERAL BIOLOGY I 1
Phylogenetic Relationship of the BRCA 1 Gene Factor
among Selected Mammal Species
May Pearl R. Martinez
KIAMBA
NATIONAL
SENIOR HIGH
DEPARTMENT
Grade 12- STEM
(Martinez)
Mindanao State University-General Santos City Graduate School
General Santos City, South Cotabato, Philippines, 9500
Introduction
Much has been learned about the role of
the breast cancer 1 or known as the BRCA1
protein in cancer development particularly in
the genetic and epidemiological approaches
since the identification of the BRCA1 gene 10
years ago. Furthermore, advances have been
made in understanding the environmental and
genetic modifiers of cancer risk associated with
BRCA1 mutations.
BRCA1 gene provides instructions for
making a protein that acts as a tumor
suppressor. As a tumor suppressor, its proteins
help prevent cells from growing and dividing
too rapidly or in an uncontrolled way which
often co tributes for the existence of cancer
cells. It is also involved in repairing damaged
DNA as stated by Wu et al. that BRCA1 is
important for DNA damage induced cell cycle
checkpoints activation. The most direct and
obvious evidence supporting BRCA1’s roles in
DNA damage response is that BRCA1
relocates to DNA damage sites and forms
nuclear foci following DNA double-strand
breaks (DSBs) (Scully et al., 1997).In the
nucleus of many types of normal cells, the
BRCA1 protein interacts with several other
proteins to mend breaks in DNA. These breaks
can be caused by natural and medical radiation
or other environmental exposures, and they
also occur when chromosomes exchange
genetic material in preparation for cell division.
By helping to repair DNA, the BRCA1 protein
plays a critical role in maintaining the stability
of a cell's genetic information (Lou et. Al,
2014).
Research suggests that the BRCA1
protein also regulates the activity of other
genes and plays an essential role in embryonic
development to every mammal. In order to
carry out these functions, the BRCA1 protein
interacts with many other proteins, including
other tumor suppressors and proteins that
regulate cell division. Breast cancer
susceptibility genes 1 and 2 (BRCA1 and
BRCA2) are found in a wide variety of
organisms and help stabilize the genome.
BRCA2 homologs and orthologues are found
in organisms across three kingdoms: animal,
plant, and fungi whereas BRCA1 homologs
and orthologues are only found in animal and
plant kingdoms. While not every organism
possesses either or both of the genes, a vast
majority do, indicating that the presence of
BRCA1/2 genes dates back to 1.6 billion years
ago when the three kingdoms were first
diverging.
Comparison of orthologous gene
sequences is emerging as a powerful approach
to expounding functionally important positions
in human disease genes. Thus using
mammalian BRCA1 sequences, this paper
evaluated the relationship of the selected data
sets to extract information from alignments
upon the varying degrees of diversity of
mammals. These data sets were also evaluated
as to determine the species that are closely
related taxa and similarities between these
closely related species are also assessed.
Multiple sequence alignment
xMultiple sequence alignment is a
crucial first step for most methods of
genealogical inference since the goal of it is to
introduce gaps into sequences so that the
columns of the aligned matrix contain character
states that are homologous which means that if
two sequences both contain a residue at a
position in the alignment, then their common
ancestor had a corresponding residue. This site
was inherited by the descendant lineages down
to the present and observed sequences and if
two sequences both have gap at a position this
does not necessarily mean that their ancestor
had no residue at that site - multiple deletion
events are possible (molevol.mbl.edu).
In this paper 44 species all coming from
the animal kingdom mostly from the class
Mammalia were selected as shown in the table
1 below. Their sequences were collected and
gathered in the National Center for
Biotechnology Information (NCBI) under
Nucleotide database. Each of the designated
species’ DNA sequences has the BRCA 1 gene
along their exon 12.
Table 1. List of 44 selected species having BRCA 1 gene studied for phylogenetic analysis.
Phylogenetic analysis on the BRCA 1 gene of
the 30 selected species
Using the Molecular Evolutionary
Genetic Analysis X, the evolutionary history of
the BRCA 1 genes from the different species
was inferred through Maximum Parsimony
method with the most parsimonious tree with
length of 7957 is shown in the Figure 1. The
tree has consistency index of 0.642674, the
retention index of 0.791474, and the composite
index of 0.625518 for all sites. The percentage
of replicate trees in which the associated taxa
clustered together in the bootstrap test with
1000 replicates is shown next to the branches.
The MP tree was obtained using the SubtreePruning-Regrafting (SPR) algorithm with
search level 1 in which the initial trees were
obtained by the random addition of sequences
with 10 replicates. This analysis involved 44
nucleotide sequences having the BRCA 1 gene.
Codon
positions
included
were
1st+2nd+3rd+Noncoding. There were a total of
82160 positions in the final dataset.
Figure 1. A phylogenetic tree of BRCA 1 gene from the 44 species listed on the table 1 was generated. The
bootstrap consensus tree inferred from 1000 replicates is taken to represent the evolutionary history of the different
BRCA 1 genes that had been analyzed.
To analyze the relationship of BRCA 1
gene DNA sequences from 44 species (Table
1) were used to derive sequence similarity and
phylogenetic
analysis.
The
overall
phylogenetic tree inferred to represent all the
44 prospective species having the BRCA 1
gene had a good bootstrap support indicating
that the derived tree truly reflects the data used
to generate it as shown in Figure 1, a Maximum
Parsimony method rendered phylogenetic tree
that shows the evolutionary relationships
between these species. It can be observed that
BRCA 1 gene of Macropus rufus, Macropus
robustus, Dendrolagus matschiei, Didelphis
virginiana, Chodsigoa hypsibia Homo sapiens,
Equus zebra, Tapirus terrestris, Rhinoceros
unicornis and Diceros bicornis which all are
from the infraclass of Marsupialia and
Eutheria, Order Perissodactyla and Primate.
Similarites in terms of their body size and
breast could be also observed. While the
Chiropodomys gliroides, Macruromys major
and Myosorex varius which have no tagging
branches on each of them signifying that there
had no descendent taxa as well as common
ancestors indicating that they are less related to
the other species in their respective clade in
terms of the aligned DNA sequence with
BRCA 1 on its exon 12 as also showed in the
Figure 2.
Figure 2. Bootstrap consensus tree of BRCA 1 gene from the 44 selected species was generated using the
Maximum Parsimony method using Molecular Evolutionary Genetic Analysis X.
Conclusion
BRCA1 gene is primary known as breast
cancer 1 gene that primarily found among
mammals with the existence of the special
gland mammary. In this study it can be
concluded that species with same body size are
more related in terms of the aligned DNA
sequence with the presence of BRCA 1 such as
with the Macropus rufus, Macropus robustus,
Dendrolagus matschiei, Didelphis virginiana,
Chodsigoa hypsibia Homo sapiens, Equus
zebra, Tapirus terrestris, Rhinoceros unicornis
and Diceros bicornis which all are from the
infraclass of Marsupialia and Eutheria, Order
Perissodactyla and Primate.
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