Exploring the Impact of Genetics on Organismal Evolution: An Analysis of

Mutations and Their Effects

Sarim Farrukh Siddicky

W.H Morden
Class 7-2

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 TABLE OF CONTENTS

Abstract
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Inquiry Question
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Introduction
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Hypothesis
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Background Research
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Observations
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Conclusion
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References
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Analysis
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Acknowledgements
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Materials/Appendix
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Abstract:

Human genes are composed of hundreds to millions of building blocks called DNA nucleotides. If even a single
nucleotide becomes mutated, there is a chance it could cause a devastating genetic disease. However, in some cases,
a mutation will actually have no effect on a human at all. In this science project, I will investigate the most common
genetic disorder, cystic fibrosis. This report will allow me to cover what types of mutations may alter the function of
a protein causing a genetic disorder and which mutations have little to no effect.

Inquiry Question:

The main focus of this research project is to try and determine why some gene mutations result in genetic disorders,
while other mutations cause little to no harm at all; what kind of genetic mutations occurring in the human genome
matter?

Introduction:

The Human Genome Project, an international research effort stretching from October 1, 1990, to April 14, 2003,
revealed that the human genome consists of approximately 20,000 to 25,000 genes. These genes are composed of
hundreds of millions of DNA monads referred to as nucleotides. Even the slightest modification in our DNA
sequence can cause a serious genetic disorder also known as a "genetic alteration". An alteration comprises
chromosome abnormalities and gene mutations. However, some mutations may not have any effects on you at all.
This depends on the type of mutation and its location.

At the time of writing, February 2023, 300+ million people worldwide are living with a genetic disorder. That
means about one out of every thirty people (depending on where you live, ethnic orientation, and other factors), is
diagnosed with a genetic disease. I’m going to be taking data from the disease “cystic fibrosis” or CF in order to
determine what kind of genetic mutations matter.

Some diseases may be fatal, some may be neutral, some silent, and some even good! In this project, I’ll be exploring
the vast topic of genetic diseases. For example as shown below:

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“The risk for having a mutation in the gene for cystic fibrosis can depend on your ethnic background (for people
without a family history of CF) as shown in the table below” (Source: https://rwjms.rutgers.edu)

Hypothesis:

I hypothesize that the reason some genetic mutations have no effect on you is that the mutation occurs in DNA that
produces a non-functioning protein. I believe this because I know that somewhere around 10 percent of our genome
is constructed of junk DNA--useless nucleotide sequences, serving no purpose that does not code for any proteins.
Given that information, I can conclude that since junk DNA is completely inconsequential to us, there should be no
effect on us in response to a change in junk DNA’s nucleotide code/composition.

Another hypothesized answer I came up with to my question was if the mutation occurred within a protein-coding
portion of a gene. This can also be called a silent mutation. Silent mutations are DNA changes in the protein-coding
region of a gene that does not affect the sequence of amino acids that make up the gene's protein therefore not
affecting the organism at all. Genes can be separated into three regions; the promoter, coding region, and
termination sequence. The promoter is the region in which the transcription of a gene is initiated. The coding region
holds all the protein-building information, and the termination sequence indicates the end of a gene. With that said, I
hypothesize that the reason some genetic mutations have no effect on you is because of the underlying fact that the
mutation occurs either in a protein-coding portion of a gene or in a junk DNA sequence.

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Background Research:

Figure: the structure of a standard human genetic code

A gene is a basic unit of heredity. Every one of these genes in our body consists of deoxyribonucleic acid
(abbreviated DNA). DNA is a genetic code, located in the nucleus (core) of your cells that is written by four types of
nucleotides: adenine (A), guanine (G), cytosine (C), and thymine (T). Most genes have multiple exons and introns
within them. An exon is a DNA sequence or RNA molecule found in a gene, which codes for a specific protein and
can be turned into mRNA (one of the three types of RNA) and then into a protein. Introns are segments of DNA or
RNA molecules located in between exons that are copied into RNA but are cut out of the final RNA transcript
therefore not coding for any amino acids.

You may be wondering what exactly RNA is. Well, this vital molecule plays an important role in the transfer of
proteins to our cells. Protein helps our body to construct and maintain healthy cells. There are three main types of
RNA, namely messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). mRNA is responsible
for giving our cells instructions on how to produce proteins. rRNA helps guide the process of translation, while
tRNA brings amino acids to the ribosome (an area outside of the nucleus of a cell), which are used to build proteins.
RNA differs from DNA in a few key ways. For example, every thymine in a DNA sequence is replaced with uracil

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(one of the four nucleotide bases in RNA). Another way the two differ is that DNA is typically composed of two
strands of sugar phosphate while RNA is usually composed of just one.

Genes can be separated into three regions: the promoter, coding region, and termination sequence. The promoter is
the region in which the transcription of a gene is initiated. It also points out which DNA strand will be transcribed
(written out). The coding region holds all the protein-building information, and the termination sequence indicates
the end of a gene (see below). All unknown vocabulary will be covered in the next couple of paragraphs.

The gene's DNA sequence is then copied to make an RNA molecule (ribonucleic acid) in a process called
transcription. Helicase, primase, DNA polymerase, and ligase are the four main enzymes involved in the replication
of your DNA.

The RNA then goes through a separate process called translation in which it turns into amino acids; the building
blocks of protein. During this process, every three RNA nucleotides code for an amino acid. A set of three
consecutive RNA/DNA nucleotides is called a codon and different codons or nucleotides may code for the same or
different types of amino acid.

Figure 1: A codon chart elucidating the type of amino acid produced from the specific codons. Notice that pro
(proline) can be coded by CCA, CCG, CCU, or CCC and that lys (lysine) is coded by either AAA or AAG.

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Essentially, a genetic code is a bunch of codons lined up that tell a cell to construct a specific protein. In the end, a
sequence of DNA has been transformed into a sequence of amino acids linked together in a long chain called a
protein. Proteins are an extremely fundamental part of our bodies as they are responsible for most of the functions of
our cells. (see figure 2)

Figure 2: The process of a gene transforming into protein

A variety of calamities may occur during this process to prevent a gene from turning into a functioning protein. As
mentioned, if even a single DNA nucleotide were to be mutated, for example from thymine (T) to an adenine (A), it
could cause severe genetic impairments and it also may cause the wrong type of amino acid to be produced. For
example, the codons CGU, CGC, CGA, and CGG all code for a specific amino acid called “Arg”. And if the wrong
amino acid is created and assembled into a long strand of amino acids, the resulting protein may be dysfunctional.
This happens because different types of different amino acids are unique in many ways in comparison to other
amino acids such as in size and the electric charges it carries. These features affect how they interact with one
another as well as the molecules that surround them (such as water and other amino acids). These seemingly small
differences can result in huge repercussions. (see figure 3)

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 Figure 3: A single-nucleotide polymorphism (SNP) in which the upper DNA molecule differs from the lower DNA
molecule at a single-base pair location; a guanine(G) / cytosine(C) polymorphism. (Courtesy of Wikipedia)

In the image above you may also notice that all guanines are paired with cytosines, all adenines are paired with
thymines, and vice versa. This is because in a standard gene, a cytosine will always pair with guanine, and evidently
thymine will always pair with an adenine. What I’m saying may contradict so some information I’ll mention in the
future.

For example, in the autosomal recessive inheritance disease, cystic fibrosis, there is a mutation in the CFTR gene.
This gene encodes for a channel that is responsible for regulating the flow of negatively charged particles, called
chloride ions either into or out of your cells. The transportation of these chloride ions helps with the secretion and
absorption of water in tissues, which is important because it is responsible for the production of mucus. Mucus is a
wet, slippery, flowing substance that helps lubricate and protect the linings of the digestive system, reproductive
system, airways, and other organs/tissues. Since chloride draws water, if chloride ions don’t get pumped into the
body, it results in the accumulation of thick and sticky mucus in the lungs and digestive tract. This mucus blocks the
airways, making it harder for the person to breathe, and it also provides an ideal environment for bacteria to grow,
leading to a number of serious health complications. For example, lung failure occurs in cystic fibrosis when
abnormally thick mucus covers the bronchioles. Bronchioles are the air tubes that keep the lungs pumping. If the
bronchioles are covered with mucus, the lungs will consequently stop functioning. Cystic fibrosis is one of the most
deadly genetic disorders because of this reason; it affects all organs that have mucus surrounding them, like (as
mentioned) the lungs. Below are some of the manifestations of cystic fibrosis: (see figure 4)

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Figure 4: the effects of cystic fibrosis on different parts of the body (image courtesy of Wikipedia Commons, 2011)

The diagnosis of cystic fibrosis can be done through genetic testing but can also be confirmed through a sweat
chloride test. A sweat chloride test is a sweat which it measures the levels of sodium and chloride (both components
of salt) in the sweat. You can even do this on your own by tasting your skin to see whether it is salty or not! Salty
skin is one of the most common symptoms of cystic fibrosis.

Cystic fibrosis is inherited in an autosomal recessive manner. Autosomal means that the gene is located on one of
the first 22 pairs of chromosomes. These first 22 pairs are called autosomes (non-sex chromosomes). Per cell, we
have 1 pair of sex chromosomes it’s on one of the first 22 pairs of chromosomes. This results in both males and
females being affected by the disease equally. Recessive means that in a pair of genes, one has to come from each
parent in order for you to be diagnosed with the genetic disorder. Hereditary diseases can be inherited in different
ways. However, the most common way is through an autosomal recessive manner as shown below: (figure 5)

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Figure 5: A graph on how prevalent different ways of inheriting genetic disorder is(source: https://www.nature.com/articles/s41431-019-0508-0)

An autosomal recessive disorder is a genetic disorder attributable to mutations of only one gene that is inherited as a
recessive allele on an autosome (non-sex chromosome). Alleles are matching genes; one from our biological father
and one from our biological mother. This means that the disease is inherited when a person receives two mutated
copies of the CFTR gene, one from each parent. Each parent must be a carrier of the gene mutation in order for a
child to be affected by cystic fibrosis.

Figure 6 (shown below) shows the cystic fibrosis inheritance pattern where “R” is the other gene (non-working
gene) and where “r” is the recessive gene (working gene). Colors correlate to inheritance in this depiction.

Looking at the image, you can see that each parent carries one defective CFTR gene (R). None of the parents are
affected though, (hence being called unaffected “carrier” father and mother) because they each only carry one
defective gene, not two. But once this parent couple reproduces and has had a child with cystic fibrosis, each
subsequent child will have a ¼ or 25% chance of inheriting the abnormal CFTR gene. This means that 75% of the
time, a child will remain unaffected. However, there is a 2/4 or 50% chance that the children are carriers of the gene
like their parents. This means that if an unaffected carrier child has children with another unaffected carrier child in
the future, the inheritance pattern for cystic fibrosis will be the same as the image shown above. In the scenario of an
unaffected carrier child having children with an unaffected child, there is a very slim chance that they will produce a
child affected with cystic fibrosis (It’s not impossible). In the end, these will always be the mathematical odds of
having cystic fibrosis. Like a coin flip, these odds aren’t always accurate; they can be enhanced or diminished.

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 Figure 6: Cystic fibrosis (or any genetic disorder) inheritance pattern (source:
https://rosalind.info/glossary/autosomal-recessive-disorder/)

To put it simply, all humans possess 46 chromosomes, which are composed of 23 pairs and consist of protein and
DNA. Each chromosome holds thousands of genes that hold our genetic codes and information, with 23
chromosomes from the mother and the other 23 from the father. The CFTR gene is located on the 7th chromosome,
and the most commonly seen mutation in this gene is called delta F508. This mutation affects the protein generated
by the CFTR gene, preventing it from transporting chloride ions into and out of cells.

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Observations:

Remember how I said that certain base pairs always match up with each other (for example, C-T and G-A)? That
may not always be the case. The occurrence of these two base pairs not pairing up is called a “mutational mismatch”
or an SNP as mentioned before. For example, the DNA base pair formed by thymine and guanine (A G-T
transversion) are able to shape-shift so that they blend in with the rest of the DNA helix…

“...When these two bases form a hydrogen bond by accident, at first, they don't fit quite right," Zucai Suo, professor
of chemistry and biochemistry at Ohio State University, said in a news release. "They stick out along the DNA helix,
so normally it's easy for the enzymes that replicate DNA to detect them and fix them."
-https://www.upi.com

And in most cases, this mutational mismatch does get caught and is rectified. But on occasion, the base pair may
modify their structure/shape before detection, disguising themselves thus evading the notice of genetic repair
mechanisms. I guess this is where they get the saying: “Fake it ‘till you make it!”

Anyway, G-T mutations can affect the way genes are expressed by making it harder for transcription factors to
recognize genes and by altering the gene's amino acid sequence. This can lead to changes in the gene's function,
which can affect the entire organism. For example, G-T mutations may result in a reduction in the expression of
important proteins, leading to reduced function of the protein. This may cause a decrease in our ability to grow and
reproduce, as well as other health consequences. G-T mutations can also lead to the formation of new proteins,
which can have unpredictable effects on the organism. Additionally, G-T mutations can affect the stability of genes,
which may lead to increased mutation rates and the potential for cancer.

Genetic alterations can have advantageous and detrimental effects depending on the kind of mutation, the
environment the affected organism inhabits, and a multitude of other factors.

Mutations take place at the DNA level and can have a variety of effects on the organism at the protein level.
Mutations are categorized into two types, depending on the level they affect: DNA-level mutations and protein-level
mutations.

DNA-level mutations can be broken down into two sections: point mutations and frame-shift mutations. Point
mutations involve the substitution of one base with another, while frame-shift mutations are the deletion or insertion
of nucleotide bases that are not codons (see figure 6). Frame-shift mutations usually have more significant effects on
the resultant protein than point mutations.

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 Figure 7: A deletion mutation in cystic fibrosis

At the protein level, there are nonsense and missense mutations. Nonsense mutations result in a termination codon
(stop codon), which sends a signal to a protein telling it when to stop its production of itself. In contrast, missense
mutations are point mutations that lead to a change in the amino acid.

Now narrowing down to the final question: What kind of genetic mutations matter?

Mutations can have harmful or beneficial effects depending on their context and location. Mutations may not only
refer to the organism it’s affecting but can also be the bacteria. However, you can’t call a mutation strictly good or
strictly bad. Some mutations can be neutral, and others can be both good and bad. Let’s take cystic fibrosis as an
example. Without much context, you may be quick to assume it's a completely bad mutation. But this mutation also
has detrimental effects. People with the CFTR mutation have a decreased risk of developing certain bacterial
infections. But in most cases, I would argue that this is a “bad” mutation. To separate these, I decided to make a
chart, providing examples of good, bad, and neutral mutations (see next page) :

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 Good Mutations (in most Bad Mutations (in most
Neutral Mutations
cases) cases)

- Lactase persistence
- Fragile X syndrome - Sickle cell anemia
- Point mutation
- Pompe’s disease - Condensation reaction
- Antimicrobial resistance
- Turner syndrome - Lactose intolerance
- Streptococcus pneumoniae
- Cystic fibrosis - Heterochromia
bacteria

Good mutation - Mutations can be beneficial or good when the mutation increases the competitive advantage or
fitness of an organism. For example, a mutation that confers antibiotic resistance in bacteria.

Example of good mutation (a): Lactase Persistence – Lactase persistence is caused by a mutation in the LCT gene.
People with the mutation have the ability to digest lactose, a sugar found in milk, more efficiently than those without
the mutation. This mutation is good for the organism which possesses it.

Example of a good mutation (b): Streptococcus pneumoniae - This mutation is only good for the bacteria infecting
the host. This is because it will be harder for the person infected to get rid of the bacteria that are resistant to certain
antibiotics. You see, streptococcus pneumoniae is a bacteria associated with pneumonia, a lung disease. To treat
pneumonia, you can take a drug called penicillin which kills the streptococcus bacteria. However, in some cases, the
bacteria can be mutated causing it to be resistant to penicillin, therefore, making it a good mutation for the bacteria,
not the organism infected by it.

Neutral mutation - Neutral mutations are mutations that occur within an organism’s genome when there is a DNA
change in the protein-coding region of a gene that does not affect the sequence of amino acids that make up the
gene's protein. Some may interpret that silent mutations are the same thing as neutral mutations, but actually, silent
mutations are a type of neutral mutation. A neutral mutation is neither good nor bad. This mutation is neutral for the
organism that possesses it.
An example of a neutral mutation: Sickle cell anemia - Sickle cell anemia is thought of as a neutral disorder, with
neither overall good nor bad effects. In some cases, it can be advantageous for adaptation in certain environments
and can even heighten fertility. Conversely, it has the potential to be disabling and can raise the chances of
mortality. The consequences of having sickle cell anemia can vary depending on the individual's particular situation
and maybe both good and bad. This mutation is neutral for the organism that possesses it.

Bad mutation - A harmful mutation defines as a genetic alteration that can cause genetic disorders that are not
“good” mutations, or cancer.

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An example of a bad mutation: is Fragile X syndrome - Fragile X syndrome is a chromosomal disorder in which the
FMR1 gene is defected. This gene is responsible for the production of a protein called FMRP which is rudimentary
for brain development. People who are diagnosed with FXS do not have the ability to produce this protein, therefore,
having cognitive impairments, learning disabilities, and/or other defects. This mutation is bad for the organism that
possesses it.

Conclusion:

In regard to my question, “Why do some genetic mutations not affect us?”, I can conclude that some genetic
mutations don’t affect us when a silent mutation occurs. Silent mutations are DNA alterations in the protein-coding
region of a gene that does not affect the sequence of amino acids that make up the gene's protein therefore not
affecting the organism at all. Silent mutations are not neutral mutations, but a type of neutral mutations. If a
dysfunctional gene causes certain amino acids to not be produced properly, a mutation is in place. In spite of that,
when mutations in the coding region of a gene occur, due to the redundancies in genetic code in the coding region of
a gene, amino acids don’t have much of an impact on the sequence of amino acids.
Therefore, I can conclude that my hypothesis was indeed correct.

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References:

CFTR gene
https://www.ncbi.nlm.nih.gov/gene/?term=cftr

DNA VS. RNA

https://www.technologynetworks.com/genomics/lists/what-are-the-key-differences-between-dna-and-rna-296719

How is cystic fibrosis inherited?

https://rwjms.rutgers.edu/departments/pediatrics/divisions/cystic-fibrosis-center/what-is-cf/genetics-of-
cf#:~:text=Cystic%20fibrosis%20(CF)%20is%20a,%22carrier%22%20of%20the%20disease.

Autosomal recessive disorder definition:

https://rosalind.info/glossary/autosomal-recessive-disorder/

What is an allele?
https://www.jax.org/news-and-insights/minute-to-understanding/what-is-an-
allele#:~:text=Well%2C%20alleles%20are%20matching%20genes,can%20often%20have%20slight%20differences.

In a given gene, what kind of DNA mutation would not change the protein that is made?
https://www.biologyonline.com/dictionary/silent-
mutation#:~:text=A%20silent%20mutation%20(quiet%20mutation,neutral%20in%20terms%20of%20evolution.

Mutation mismatches:
https://www.upi.com/Science_News/2018/02/01/Study-reveals-secrets-of-DNA-
mutation/4741517508834/#:~:text=The%20DNA%20base%20pair%20formed,the%20DNA%20ladder%2C%20or
%20helix.

Different types of mutations:

https://www.khanacademy.org/test-prep/mcat/biomolecules/genetic-mutations/v/the-different-types-of-mutations

Effects of mutations:
https://www.youtube.com/watch?v=JxC2phkdY8Y

Silent mutations:
https://www.biologyonline.com/dictionary/silent-mutation

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Analysis:

In the making of this project, I encountered many challenges and issues each of which were equally intriguing, but
in this section, I’m only going to shed light on to only one of them which was trying to interpret this synopsis into
words I and people who don’t have a vast knowledge on this topic can easily understand. I’ve scanned countless
google definition banks in order to summarize the gist of my topic in these seventeen pages which in the end,
worked out pretty well for me. Also, I found correcting the formatting in Google Docs to be quite a rigorous process,
but I eventually resolved that problem. In spite of further reflection, I’ve come to realize that I haven’t quite grasped
the concept of everything about this topic, but hopefully, in the future, I’ll be able to have a more thorough
understanding of the broad world of genetics.

Acknowledgments:

I would like to dedicate this section to thanking my math/science teacher, Mr. Abbazhadeh for providing our class
(and me) with amazing resources to help us plan the science fair project, as well as various student templates to
aspire from. I would also like to thank my dad and uncle for encouraging me to do this project in the first place by
finding many resources and articles which I used during the making of this project.

Materials/Appendix:

All of the research from this project was conducted using Google.ca. I also used Google Docs, a computer with
internet access, a keyboard, a mouse, and an obscene amount of NON-copyright websites I managed to find.

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