INTRODUCTION

Natural selection acts on phenotypes, which are largely shaped by genotypes. Because of this relationship, gene
frequencies change as phenotypes are selected for or against within a population. Genes that code for beneficial traits
tend to accumulate in populations. Similarly, genes that code for traits that reduce an individual’s fitness tend to decrease
in frequency. But how do new genes arise? And once they arise, do they ever change? Can once-functional genes
become useless and “die”? And can “extra” genes take on new functions? This lesson explores the mechanisms of gene
birth and death and provides several examples of the role these processes play in evolution.

MATERIALS
● student presentation slides
● Internet connection for hyperlinks
● genetic code chart (in the BANK or the last page of this handout)

PROCEDURE

1. In order to complete this lesson, you will need to access the accompanying presentation slides titled “Mutations and the
Birth and Death of Genes.”

2. As you proceed through the slides, they will prompt you to answer the questions in this handout. Some answers will
require you to apply what you learn from watching the animations, lecture clips, and short films embedded in the slides.

QUESTIONS

1. What drives the evolution of new genes?

Gene duplication drives new genes.

Define “mutation.”
A mutation is a change in an organisms genetic information or DNA.

Are mutations random?

Mutations are random.

2. Which of the following has the greater potential effect on the evolution of a population: mutations in somatic
(body) cells or mutations in gametes (egg and sperm)? Explain.
Mutations in body cells have less effect because it only affects the individual in which they occur. If that occurs
in gametes, however, that can be passed to the next generation.

3. What is a point mutation?

A point mutation is when a single nucleotide changes.

4. When can an insertion or deletion be something other than a point mutation?

It is possible if it involes two or more nucleotides.

5. DNA is transcribed to messenger RNA (mRNA), which is translated into a sequence of amino acids that fold to
form a protein.
 a. Complete the tables below by first transcribing the DNA triplets to mRNA codons and then translating
them to amino acids by using a genetic code chart on page 8 of this handout.
Wild-Type DNA Sequence
DNA GAC TCT GGA CAC CTC

mRNA CUG AGA CCU GUG GAG

Amino Acid Leu Arg Pro Val Glu

Mutant DNA Sequence 1

DNA GAC TCT GGA CGC CTC

mRNA CUG AGA CCU GCG GAG

Amino Acid Leu Arg Pro Ala Glu

Mutant DNA Sequence 2

DNA GAC ACT GGA CAC CTC

mRNA CUG UGA CCU GUG GAG

Amino Acid Leu stop

b. Which mutant sequence contains a missense mutation? Explain your answer.

The second one has a missense mutation because only one amino acid changed.

c. Which mutant sequence contains a nonsense mutation? Explain your answer.

The third one has a nonsense mutation because it is stopped prematurely.

6. Which type of substitution mutation has the greatest chance of leading to a nonfunctional protein? Explain your
answer.
A nonsense mutation has the greatest chance of this because it stops the whole sequence.

7. Describe the cause of sickle cell anemia. (Animation from slides)

Valine causes the cells to elongate oddly. This makes them break.

8. Rett syndrome occurs almost exclusively in girls, but there are a few male patients. The right side of slide 10
depicts the normal protein (A) and the proteins produced by three different MECP2 mutations, (B,C, and D) along
with the resulting phenotypes of the male Rett syndrome patients. The top illustration (A) shows the healthy
protein with the most important domains highlighted in light blue and pink. The orange band in the bottom
illustration (D) indicates the presence of a different amino acid in the protein sequence compared to the normal
protein. (lecture clip on Rett syndrome)
a. What type of substitution mutation would result in the protein structures shown in B and C?
Nonsense mutation

b. Even though the proteins depicted in B and C are caused by the same type of mutation, patients with the
mutation depicted in the third illustration have less-severe symptoms. Develop a hypothesis to explain
why.
I think this may be because the translation of protein B is stopped before the one the protein in C is
 stopped. So, the protein is much shorter. The protein can’t carry out its full function to the same
capacity that C can.

c. What type of substitution mutation causes the protein depicted in D?

Point mutation

d. Form a hypothesis to explain why patients with the mutation depicted in D have less-severe symptoms
than patients with the other type of mutation.
The protein has a complete sequence in D. It is able to therefore perform all functions.

e. There are many more female patients with Rett syndrome than males; furthermore, female patients
exhibit a much wider range of symptoms than males do. Explain both observations. (Hint: Think about
what you know about the X chromosome; you may also watch the X Inactivation animation.)
More female patients with Rett syndrome survive. This is a major reason. Also, they have more
symptoms exhibited because the expression of the two X chromosomes is different.

9. The following sequence contains an insertion mutation, shown in the larger, red font.
a. Use the genetic code chart to complete the table below.

DNA GAC CTC TGG ACA CCT

mRNA CUG GAG ACC UGU GGA

Amino Acid Leu Glu Thr Cys Gly

b. Compare this amino acid sequence to the wild-type sequence in Question 5. Explain why frameshift
mutations can have such major consequences on a protein’s function.
They mess up all future amino acids too.

10. What is a trinucleotide repeat?

That’s when sequences of 3 nucleotides repeat several times. It makes the chormosome thin.

11. After watching the 14-minute lecture clip regarding spinocerebellar ataxia type 1 (SCA1) on slide 13, answer the
following questions.
a. What type of mutation causes SCA1, and how does the mutation occur?
It is a trinucleotide repeat expansion.

b. Explain how the number of CAG repeats relates to the severity of the disease.
It causes the chromosome to get thin and cause malfunctioning of the nerve fibers that carry messages
to the brain.

c. What is another human disease caused by a trinucleotide repeat expansion?

Huntington disease is a another example.

12. Many people mistakenly think that “all mutations are bad.”
a. Explain how it is possible for a mutation to have no effect on an organism.
It can be a silent mutation so it doesnt change the amino acid its supposed to code for.

b. Use a real example to explain how a mutation can have a positive effect on an organism.
 Peppered moths were able to hide on trees and avoid predators better because they were now dark.

13. When in the cell cycle do most chromosomal alterations that affect chromosome structure occur?
Usually it occurs during the S phase of interphase of prophase I of meiosis.

14. List and describe the four types of alterations that affect chromosome structure.
a) Chromosomal deletions occur when part or all of a chromosome is lost.

b) Chromosomal inversions occur when a segment of a chromosome breaks off and reattaches in the reverse
orientation.

c) Chromosomal translocations occur when a part of a chromosome breaks off and attaches to a
nonhomologous chromosome.

d) Chromosomal duplications occur when part or all of a chromosome is repeated.

15. How might these chromosomal alterations affect gene expression? (Hint: Watch the Gene Switch animation at
http://www.hhmi.org/biointeractive/gene-switch.)
The position of the genes can change. So, how it is regulated also needs to be change.

16. What type of chromosomal alteration causes cri-du-chat syndrome? How do you know?
Chromosomal deletion causes this. We know this because we can see the part that was deleted from the
chromosome.

17. View the four-minute lecture clip and animation on slide 18. (Note: Gleevec is a pharmaceutical drug developed
to help treat chronic myelogenous leukemia, or CML.)
a. What type of chromosomal alteration causes CML?
translocation

b. Which chromosomes are affected by this meiotic error?

Chromosomes 9 and 22

c. What is the “Philadelphia chromosome”?

It is a mutated version of chromosome 22

d. Explain the mechanism by which Gleevec works to treat CML.

It prevents phosphorylation. The abnormal cell growth is stopped because of this.

18. Define “paralogous genes” and explain the evolutionary significance of gene duplication.
Paralogous genes are pairs of genes in an organism. Gene duplication helps for there to be more diversity in
life.

19. Describe the possible outcomes of gene duplication.

Functions can be lost or gained. Basically, it can either be beneficial or not. Or, it could be something that is
neutral.

20. Explain how gene duplication led to the evolution of a key mammalian trait.
The duplicated lysozyme gene can lead to novel functions.
21. What is a pseudogene?
Noncoding gene

22. Explain how the accumulation of mutations could lead to gene death.
If enough structures are changed, the protein is not functional anymore. If these mutations continue, it will die.

23. Develop hypotheses to explain the evolutionary significance of the gene death events for the examples listed
below.
a. Olfactory receptor genes in humans and mice
Mice have a better sense of smell than humans do because of the different rates at which the senses
developed.

b. Myoglobin gene in some icefish species

Fish are less able to deliver oxygen throughout their bodies because of the gradual loss of myoglobin
genes.

24. Explain the evolutionary significance of icefish “antifreeze” proteins. What types of chromosomal rearrangements
and gene mutations led to the development of the antifreeze protein? (Hint: Watch the animation about the
ancestral and antifreeze gene in the film very closely. Three mutation events follow the initial gene duplication.)
Provide evidence from the animation to support your answer.
Antifreeze allows the icefish to keep their blood flowing despire the water being extremely cold. A chromosomal
duplication had a gene duplication. Then a deletion occurred. The replication of a repeated DNA sequence and
an insertion caused there to be the gene that codes for the antifreeze.

25. What “gene death” event occurred in icefish?

This event for them would be when the genes for globin polypeptides were lost.

How did it affect their ability to survive and reproduce?

It enhanced their survival because it made it easier to pump blood even in the freezing temperatures of their
environment.

26. Explain how icefish serve as an example of both the birth and death of genes. Provide evidence from the case
study to support your answer.
Genes that code for the antifreeze were born. Genes for the hemoglobin molecules died.

27. Using what you know about the icefish genome and providing evidence from the cast study, explain this
statement: “Genes tell the story of evolution.”
Genes are the small parts living in each organism that describe how and when evolution occurred roughly. They
are a measure of what happened as it went on, as well as what things are beneficial to organisms and what
things are not.