The Molecular Evolution
of Gene Birth and Death
Author:
Ann Brokaw
AP Biology Teacher
Rocky River High School
Rocky River, Ohio
The Birth and Death
of Genes
To the student:
The following slides provide
examples of how genes can be
gained and lost through
evolution.
Answer the questions on the
student handout when
prompted.
The Birth of Genes
Mutations are the ultimate source of new genes.
A mutation is a change in an organism’s genetic
information, or DNA.
Mutations occur at random. When mutations occur
in genes, they may result in new phenotypes that
natural selection acts upon.
Student Handout:
Answer Question 1
Heritable Mutations
Mutations can occur at any time and in the
DNA of any type of cell. Mutations that occur in
somatic (body) cells only impact the individual
in which they occur. Mutations that occur in
gametes (egg and sperm) can be passed on to
the next generation.
Student Handout:
Answer Question 2
Types of Mutations
Mutations can occur on a small
scale, most often affecting one or
two nucleotides of DNA, or can
involve large segments of a
chromosome or even an entire
chromosome.
Regardless of the type, mutations
in a gene’s DNA can alter the
function of the protein encoded by
the gene.
Point Mutations
Most mutations involve changes to a single nucleotide
or a few nucleotides of an organism’s DNA.
Point mutations are changes in a single nucleotide of
the DNA sequence. They include substitutions,
insertions, and deletions.
Insertions and deletions are not only point mutations;
they can involve two or more nucleotides.
Student Handout:
Answer Questions 3 - 4
Substitutions
A substitution mutation is the replacement of a single
nucleotide with another. It can be classified in one of three
ways depending on the effect it has on the protein
produced:
• Silent mutations have no effect on the protein.
• Missense mutations result in a single amino acid
change in the translated sequence.
• Nonsense mutations result in an amino acid codon
being replaced by a “stop” codon. Nonsense
mutations cause a premature end to translation,
resulting in a truncated protein.
Substitution Examples
Wild-type
(unmutated)
Silent
mutation
Missense
mutation
Nonsense
mutation
DNA
G-T-C
G-T-T
G-T-G
A-T-C
mRNA
C-A-G
C-A-A
C-A-C
U-A-G
Amino
acid
Glutamine
Glutamine
Histidine
“Stop”
Student Handout:
Answer Questions 5 - 6
Sickle Cell Anemia
Sickle cell anemia is a disease caused by a point mutation
that affects the shape of red blood cells. People with sickle
cell anemia, which is also called sickle cell disease,
experience frequent pain, infections, and other symptoms.
Click to view an animation on
sickle cell anemia
A.
B.
C.
From the BioInteractive.org website:
http://www.hhmi.org/biointeractive/dna/
DNAi_sicklecell.html
Student Handout:
Answer Question 7
Rett Syndrome
Rett syndrome is a disorder that primarily affects girls and causes
severe problems with communication, learning, and coordination. The
most common cause of Rett syndrome are mutations in the MECP2
gene on the X chromosome. This gene provides instructions for making
a protein that is critical for normal brain function.
Click to view a lecture clip
on Rett syndrome
A.
A.
B.
B.
From the BioInteractive.org website:
www.biointeractive.org/neuroscience/
child_dev+rett.html
Student Handout:
Answer Question 8
C.
C.
D.
D.
Insertions and Deletions
Insertion and deletion mutations occur when one or more
base pairs are inserted or deleted from the DNA sequence.
Since mRNA is translated three nucleotides at a time,
insertions and deletions that do not involve three or multiples
of three nucleotides change how all the mRNA downstream
of the mutation is translated. These mutations are known as
frameshift mutations. Frameshift mutations almost always
result in a nonfunctional protein.
Student Handout:
Answer Question 9
Repeat Expansion
Some protein-coding genes contain sequences of
three nucleotides, repeated several times. This type
of repeat is called a trinucleotide repeat. The
number of repeats can increase, or “expand,” due to
an error during DNA replication. The repeat
expansion gives rise to a new allele but can still
result in a functioning protein. However, if the number
of repeats exceeds a certain “normal” threshold for
that gene, the resulting protein will no longer function
properly.
Student Handout:
Answer Question 10
Spinocerebellar Ataxia Type 1
An example of a disease caused by
a trinucleotide repeat expansion is
spinocerebellar ataxia type 1
(SCA1). SCA1 is an inherited
disease of the central nervous
system. The mutations cause
malfunctioning of the nerve fibers
that carry messages to and from the
brain. The overall result is
degeneration of the cerebellum, the
coordination center of the brain.
Click to view a lecture clip on
spinocerebellar ataxia type 1
From the BioInteractive.org website:
http://media.hhmi.org/hl/03Lect3.html?star
t=12:26&end26:16
Student Handout:
Answer Question 11
Are All Mutations “Bad”?
It is a common misconception that “all mutations are bad.” We
have already learned that some mutations in genes have no
effect, such as silent mutations, whereas others cause disease.
But mutations can also be beneficial to an organism.
Here is an example:
View the short film
The Making of the Fittest:
Natural Selection and Adaptation
From the BioInteractive.org website:
www.biointeractive.org/shortfilms
Student Handout:
Answer Question 12
Chromosomal Alterations
Changes to the number or structure of chromosomes can
also affect an organism’s phenotype. Such large-scale
changes most often occur during the S phase of interphase,
when DNA is replicating; during prophase I of meiosis, when
crossing over occurs; or upon exposure to damaging agents,
such as radiation.
There are four main types of alterations in chromosome
structure: deletions, inversions, translocations, and
duplications.
Student Handout:
Answer Questions 13 - 14
Types of Chromosomal Alterations
• Chromosomal deletions occur when part or all of a
chromosome is lost.
• Chromosomal inversions occur when a segment of
a chromosome breaks off and reattaches in the
reverse orientation.
• Chromosomal translocations occur when a part of
a chromosome breaks off and attaches to a
nonhomologous chromosome.
• Chromosomal duplications occur when part or all
of a chromosome is repeated.
Student Handout:
Answer Question 15
Cri-du-chat Syndrome
Cri-du-chat is a rare disorder caused by a
chromosomal alteration on chromosome 5. Infants with
this condition often have a high-pitched cry that
sounds like that of a cat. A drawing of an affected
individual’s chromosome 5 is shown below.
Student Handout:
Answer Question 16
Chronic Myelogenous Leukemia
Chronic myelogenous leukemia (CML) is a rare form of cancer
caused by a chromosomal alteration that occurs in somatic cells. It is
characterized by increased and unregulated growth of myeloid cells in
the bone marrow and the accumulation of these cells in the blood.
Click to view a lecture clip on
chronic myelogenous leukemia
Click to view an animation on
CML and Gleevec
From BioInteractive.org website:
www.biointeractive.org/dna/DNAi_cml_gleevec.html
From the BioInteractive.org website:
http://media.hhmi.org/hl/03Lect2.html?start=32:20
&end36:11
Student Handout:
Answer Question 17
A Closer Look at Duplications
Chromosomal duplications occur when all or part of a
chromosome is repeated, resulting in two copies of a gene or
genes.
Two genes are said to be paralogous if they exist at different
chromosomal locations in the same organism and if they
arose from a common ancestral gene.
Gene duplication can lead to new traits and has played a
major role in the evolution and diversification of life.
Student Handout:
Answer Question 18
Causes of Gene Duplications
 Mechanisms by which complete genes are duplicated
include:
 Unequal crossing over: Chromatids from
homologous chromosomes are misaligned during
crossing over in prophase I of meiosis, causing one
chromatid to gain a second set of genes from the
homologous chromatid.
 Chromosome breaks: A piece of a chromosome
breaks off and becomes attached as an extra segment
to another chromosome during meiosis.
 Retrotransposition: mRNAs are reverse transcribed
into DNA, and these reverse copies of genes are
inserted at random sites in the genome.
Gene Duplication Outcomes
 When a gene is duplicated:
 one of the two gene copies can lose its function by
accumulating mutations over generations.
 one of the two gene copies can gain a novel function
through subsequent mutation; this can only happen if
the original gene duplication event does not have
severe effects on the organism and can persist over
generations.
 the two copies of the gene can partition the total
function of the ancestral gene into two unique but
related functions for more efficient expression.
Student Handout: Answer Question 20
Duplicated Genes in Animals
Lysozyme is an enzyme in animals
that protects against bacterial
infection by hydrolyzing the cell
walls of bacteria. α-Lactalbumin is
a nonenzyme protein that plays a
role in mammalian milk production.
Both proteins have similar amino
acid sequences and threedimensional structures. They are
both present in mammals, but only
lysozyme is present in birds.
Student Handout: Answer Question 21
Duplicated Genes in Flowering Plants
The flowering plant genes P1 and
paleoAP3 are involved in stamen
development. Scientists have
traced the origin of these genes to
the duplication of a gene called
MADS. This duplication took place
prior to the evolution of flowering
plants.
More recently, the paleoAP3 gene
duplicated again. The new gene
evolved a novel function in petal
development.
Student Handout:
Answer Question 22
Other Examples of Duplicated Genes
The following examples of gene duplications demonstrate the
evolutionary significance of these events:
Human olfactory genes
Early mammals carried a single gene for detecting odors; today,
humans have 1,000 olfactory receptor genes.
Genes that break down RNA
Most primates have one gene for the pancreatic enzyme RNAse,
which breaks down dietary RNA and degrades double-stranded
RNA, perhaps as a defense against viruses. The colobine monkey,
douc langur, has two genes that produce two RNA-degrading
enzymes—RNAse1 and RNAse1B—which work best at different pH
levels. Douc langurs primarily eat leaves, and the new gene
improved the efficiency of digestion.
Student Handout: Answer Questions 23
The Death of Genes
Duplication can lead to new genes. But genes can also
lose their protein-producing abilities or stop being
expressed. Such genes are called pseudogenes, or
“molecular fossils.” As species have evolved, diverged,
and gone extinct, so too have their genes.
Genes become pseudogenes when they accumulate
mutations over long periods of time. Note that this only
happens if the mutations do not compromise the
organism’s survival, or else natural selection would
eliminate the mutations.
Student Handout: Answer Questions 24 - 25
Examples of Gene Death
There are several examples of genes losing their functions that
demonstrate the evolutionary significance of these events.
Olfactory receptor genes in humans and mice
Mice have about 1,500 olfactory receptor genes, while humans
have about 1,000. Only 20 percent of mouse olfactory receptor
genes are pseudogenes, compared to about 60 percent in
humans.
Myoglobin gene in some icefish species
Myoglobin is an oxygen-binding protein found in muscles,
similar to hemoglobin in red blood cells. Myoglobin is absent
from muscles, including the heart, of several, but not all, icefish
species.
Student Handout:
Answer Question 26
Gene Birth and Death in Icefish
Icefish provide an excellent example of both
the birth and death of genes.
Click to view the short film The Making of the Fittest:
The Birth and Death of Genes
From the Biointeractive.org website:
www.biointeractive.org/shortfilms
Student Handout:
Answer Questions 27 - 30
Evolutionary Significance of
Gene Birth and Death
“Natural selection acts only in the moment.
It cannot preserve what is no longer used,
and it cannot plan for the future.”
Dr. Sean Carroll, Into the Jungle
Student Handout:
Answer Questions 31 - 34
Resources:
 Campbell, Neil A. and Jane B. Reece. Biology, AP Edition. Eighth Edition. Pearson
Benjamin Cummings Publishing. San Francisco, California. 2008.
 Carroll, Sean B. In Cold Blood: The Tale of the Icefish, Chapter 9, Into the Jungle,
Benjamin Cummings, San Francisco, California. 2008.
 Deng, Cheng, et al. Evolution of an Antifreeze Protein by Neofunctionalization Under
Escape from Adaptive Conflict. Proceedings of the National Academy of Sciences,
Vol. 107, No. 50. December 14, 2010.
 Howard Hughes Medical Institute, 2003 Holiday Lectures on Science, Learning from
Patients – The Science of Medicine, Chevy Chase, Maryland, 2003.
 Howard Hughes Medical Institute, Making of the Fittest: Natural Selection and
Adaptation, Chevy Chase, Maryland, 2011.
 Howard Hughes Medical Institute, Making of the Fittest: The Birth and Death of
Genes, Chevy Chase, Maryland, 2011.
 Howard Hughes Medical Institute, www.BioInteractive.org, DNA animations, Chevy
Chase, Maryland, 2011.
 Hurles, M. Gene Duplication: The Genomic Trade in Spare Parts. PLoS Biol. 2(7):
e206. doi:10.1371/journal.pbio.0020206, 2004.
 Raven, Peter H. and George B. Johnson. Biology. Ninth Edition. (McGraw-Hill
Publishing. New York, New York. 2011.)
 Zhang, Xhang, et al. Gene Duplication Adapts to Changing Environment. Nature
Genetics (online). March 4, 2002.