Content Benchmark L.8.A.2
Students know changes in genes of eggs and sperm can cause changes in inherited characteristics. E/S
Mutation is a term that is often associated with negative or unusual consequences. The media uses mutations as an entertaining theme to the plots of many shows such as Heroes, X-men,
Spiderman, and Teenage Mutant Ninja Turtles. The main characters in these shows have undergone radical transformations or developed super human powers due to a mutation of their
DNA. It is understandable that students will draw upon the information presented in these shows and develop misconceptions related to the terminology associated with changes in genes and inherited characteristics. Mutations are changes in the DNA sequence that may or may not cause an effect on an organism. Due to the nature of DNA and protein synthesis, most mutations cause no change in the function of an organism. However, there is the possibility that mutations may be beneficial or harmful (possibly fatal) to an organism. Random mutations naturally occur in populations and may or may not be passed along to the next generation. Mutations are considered one of the driving forces of evolution because they cause change in populations over time. The traits that parents pass along to their offspring are distributed through their gametes
(egg/ovum or sperm cells). Only changes that occur in the DNA of these cells will affect the inherited characteristics of their offspring.
Mutations and Inheritance
Members of the same species are remarkably similar in terms of their DNA sequences. In fact, their DNA sequences differ by approximately one base out of every thousand. “Each DNA difference results from a mutation- ranging from single nucleotide changes, to small repeated units, to large insertions or deletions. Some mutations generate novel changes that are the starting point of evolution, and some are responsible for disease” (Dolan DNA Learning Center, http://www.dnaftb.org/dnaftb/27/concept/index.html
). Most mutations that occur in humans affect areas of the genome that are not expressed. Therefore, a majority of mutations do not have an obvious immediate effect on our overall health or evolution. In fact, the average person has inherited hundreds of mutations from their ancestors and will acquire approximately 30 new mutations in their lifetime. Only the mutations that occur in the gametes will be passed on to the offspring.
For more information related to mutations accumulated over your lifetime, go to http://www.hhmi.org/genetictrail/d100.html
It is easier for humans to observe the effects of mutations in organisms that have relatively short life spans. For example, the overuse of antibiotics has led to the evolution of antibiotic resistant strains of bacterial pathogens. Throughout generations, bacteria have mutated in ways that the medicines commonly used to disrupt their biological processes no longer have an effect on them.
Figure 1 shows a cartoon version of bacteria becoming resistant to antibiotics through random mutations. A similar case has occurred among insects and their resistance to pesticides. Due to mutations, changes in the insects make them resistant to the chemicals that were used to kill them. Although the changes in these organisms are a nuisance to humans, the mutations are beneficial to the survival of the bacteria and insect populations.

Antibiotics attack and kill off bacteria
The mutated ones survive after the antibiotics are gone...
...and reproduce, passing along the mutation
Eventually there are more antibioticresistant without the mutation.
to their offspring. bacteria than nonresistant.
Figure 1 . Cartoon depicting bacteria mutating to become antibiotic resistant. ©Eric MacDicken
(From http://www.microbeworld.org/know/mutations.aspx
)
A genetic mutation is a change in the sequence of DNA. Changes in the DNA sequence may be caused by errors in the reading of the genetic code or environmental mutagens (substances that cause mutations). When changes occur in a somatic (body) cell, only the individual organism is affected. However, if the mutation occurs in a germ (sex) cell, then that change may be passed on to the individual’s offspring. The only genetic information that is passed from one generation to the next is located in the gametes (ova and sperm cells). For example, if an individual develops skin cancer due to exposure to a mutagen such as too much UV radiation, their offspring will not have skin cancer because the mutation occurred in the parent’s skin cells and somatic (body) cells are not used in fertilization. On the other hand, if the mother’s ovum (egg) undergoes an error during cell division and an extra #21 chromosome is present, then the child will develop
Downs Syndrome due to the extra chromosome. Normally, the ovum and sperm each contain 23 chromosomes which combine to form 46 chromosomes (23 pairs) after fertilization. If the ovum encountered an error during cell division, and an extra chromosome is present, the result would be 24 chromosomes (in ovum) + 23 chromosomes (in sperm) = 47 chromosomes in the offspring. An extra #21 chromosome results in Down Syndrome (also known as Trisomy 21).
See Figure 2 for a karyotype (photomicrograph of chromosomes) of an individual with Down
Syndrome. An individual normally receives one copy of each chromosome from each parent.
The presence of the extra #21 chromosome results in learning disabilities and physical symptoms characteristic of this disorder.

Figure 2 . Karyotype of an individual with Downs Syndrome (Trisomy 21). Note the 3 copies of chromosome #21.
(From http://encarta.msn.com/media_461569106_761556944_-1_1/Down_Syndrome_-_Trisomy_21.html
)
Chromosomes are composed of DNA, which contains the information necessary for an organism to function properly. DNA has a variety of roles including regulating genes and coding for proteins. Some sections of DNA are not expressed and their function remains unknown at this time. DNA is a molecule that contains four nitrogen bases: adenine (A), thymine (T), guanine
(G), and cytosine (C). The nitrogenous bases make up the “code of life” or the “blueprint of the organism.” Figure 3 shows a model of the double helix DNA molecule with its four nitrogenous bases.

Figure 3.
Model of the DNA molecule showing the four nitrogenous bases.
(From http://evolution.berkeley.edu/evolibrary/article/0_0_0/mutations_02 )
One of DNA’s primary roles is providing the information needed in the production of proteins. A simplified version of protein synthesis involves each three-base sequence of expressed DNA being transcribed into a codon of mRNA. The mRNA codon then pairs with a corresponding tRNA anticodon that is associated with a specific amino acid. Figure 4 shows a codon of GCA which stands for guanine, cytosine, and adenine. This codon translates into, alanine, which is one of twenty amino acids.
Figure 4 . Codon representing alanine.
(From http://evolution.berkeley.edu/evolibrary/article/0_0_0/mutations_02 )
Amino acids bond together in different ways to form the thousands of proteins that are necessary for life to exist. Figure 5 shows a chart used to decode the amino acids according to the codon.
(When DNA base pairs with RNA, thymine is substituted by uracil [U] in RNA. If the DNA sequence changes due to a mutation, then the protein may also change or not form at all).

Figure 5 . Circle chart to decode the 20 amino acids using the mRNA codon.
(From http://www.biology.lsu.edu/heydrjay/1201/Chapter17/SCI_Amino_Acid_CIRCLE.jpg
)
An illustration and overview of the process of protein synthesis is shown in Figure 6.
Figure 6 . Overview of the process of protein synthesis.
(From http://www.nature.ca/genome/03/c/10/03c_13a_e.cfm
)

Although knowing the process of protein synthesis is not a performance indicator for a middle school student, it is necessary background information for a teacher to explain how DNA contains the “code of life.”
For a detailed explanation of protein synthesis see TIPS Benchmark L.12.A.2.
How Mutations Occur
Mutations may occur due to an error as the DNA template is being replicated during cell division
(See Figure 7). Approximately one “naturally occurring” mistake occurs for every 100,000,000 bases of DNA that are read. However, cells contain proofreading DNA repair enzymes that fix a majority of the mistakes. If a base is paired incorrectly, the repair enzyme usually corrects the problem. (See http://learn.genetics.utah.edu/units/disorders/sloozeworm/mutationbg.cfm
for more information on DNA repair enzymes). If the mistake is not corrected, then the mutated copy of DNA will be passed along to each successive generation of daughter cells. If the mutation occurs in a gamete (ovum or sperm cell), then the offspring will inherit the mutation.
An explanation of the range of possible effects of germ cell mutations is available through http://evolution.berkeley.edu/evolibrary/article/0_0_0/evo_19 .
An animation of a mutation occurring during DNA replication is available at http://www.sciencemuseum.org.uk/on-line/lifecycle/82.asp
.
Figure 7 . Mutation occurring during DNA replication.
(From http://evolution.berkeley.edu/evolibrary/article/0_0_0/mutations_04 )
Environmental mutagens such as toxic chemicals, nuclear radiation, and UV light can alter the
DNA structure by changing the nitrogen bases. When a base is altered, it may cause incorrect base pairing. In a DNA molecule, adenine (A) bonds thymine (T) and cytosine (C) bonds with guanine (G). Figure 8 illustrates the effects of an environmental mutagen on the structure of
DNA. The environmental agent alters the cytosine of the first base pair. This causes guanine to incorrectly bond with thymine in the resulting DNA strand. During DNA replication, exact copies of DNA are supposed to be formed. However, the mutation has causes a permanent change in the DNA strand which will be passed along each time the cell replicates.

Figure 8 . The effects of an environmental agent on DNA.
(From http://learn.genetics.utah.edu/units/disorders/sloozeworm/mutationbg.cfm
)
Types of Mutations
The effect of a gene mutation depends upon the type of mutation that has occurred. If only one or a few DNA bases are affected, then it is known as a point mutation. One nucleotide of the DNA may be substituted by another resulting in a change at that point of the DNA sequence.
Substitution point mutations typically affect only one amino acid. If a nucleotide is deleted or

added into the DNA sequence, then a frameshift mutation occurs. The DNA sequence is still read in triplets, but the coded information has shifted due to the insertion or deletion. Since the reading frame of the DNA sequences has shifted, these mutations are known as frameshift mutations. Every amino acid that follows the point of mutation is affected by a frameshift mutation. Frameshift mutations are more serious because they may cause an entirely different protein to form or no protein to form at all. See Figure 9 for an illustration of different types of mutations. The original protein fictionally coded for the word “Note.” After a series of mutations, the coded word changed its meaning or created a word that does not mean anything.
Figure 9 . Different types of mutations.
(From http://www.nature.ca/genome/03/c/10/03c_14_e.cfm
)
The sickle cell point mutation is an example of a mutation that can have positive and negative effects. Sickle cell anemia is caused by a point mutation where one base is substituted and causes a drastic change in the structure of the hemoglobin (protein that carries oxygen in red blood cells). By changing one base, one amino acid changes and causes the hemoglobin protein to clump. This negatively results in red blood cells shaped like sickles instead of the normal round biconcave shape. The sickled red blood cells interfere with normal blood flow because they do

not travel through the blood vessels as well as the round red blood cells. If an individual inherits two mutated copies of the sickle cell gene, then the individual will have sickle cell anemia and experience the symptoms associated with interrupted blood flow. However, individuals who inherit only one gene for the sickle cell trait are resistant to malaria. Inheriting one copy of the sickle cell mutation is only beneficial if the individual lives in an area where malaria is prevalent.
For a detailed explanation of the cause of sickle cell anemia with diagrams, please go to http://evolution.berkeley.edu/evolibrary/article/side_0_0/sicklecase_01 .
Finally, there are mutations that involve the entire chromosome. These mutations may cause changes in the location of genes or the number of genes. Figure 10 shows the types of chromosomal mutations that may occur including deletion, duplication, inversion, and translocation.
Figure 10 . Examples of chromosomal mutations.
(From http://www.nature.ca/genome/03/c/10/03c_14_e.cfm
)
For a more thorough explanation of the types of mutations see TIPS Benchmark L.12.A.4

Although most mutations that occur in organisms cause no effect at all, some mutations cause a disruption in the normal biological processes which then affect the organism. When mutations occur in the gametes, then the resulting offspring will be affected.

Content Benchmark L.8.A.2
Students know changes in genes of eggs and sperm can cause changes in inherited characteristics. E/S
Common misconceptions associated with this benchmark
1.
Students incorrectly associate the term mutation with harmful consequences and do not realize they can be beneficial to the organism.
In fact, mutations can be beneficial. However, most mutations cause no change in gene function. The claim that "almost all mutations are harmful" is false. Mutations provide a population with genetic diversity. According to the Howard Hughes Institute, the average person has inherited hundreds of mutations from their ancestors and will develop 30 new mutations within their lifetime due to errors in reading the genetic code or environmental conditions. Some of these acquired mutations are passed along to the offspring. For more information, go to http://www.hhmi.org/genetictrail/d100.html
.
2.
Students incorrectly believe that mutations are caused by selective forces in the environment.
Students have the misconception that organisms willingly mutate in response to a change in their environment. Mutations are natural and occur randomly. A genetic change is passed to members of a population by transmission from parents to offspring. Therefore, a whole population cannot change at once. Environmental conditions may determine if a trait is beneficial or detrimental, however, it does not cause a trait to evolve within a population.
For a detailed explanation of random versus directed mutations, visit http://evolution.berkeley.edu/evolibrary/article/0_0_0/mutations_07 .
3.
Students incorrectly think that an individual adult can radically change features due to mutations in their DNA.
This misconception may be the result of students incorporating the ideas presented in entertainment and incorrectly applying it to genetics. Students may watch movies such as
Spiderman, X-men, or Teenage Mutant Ninja Turtles and develop such misconceptions.
It is possible for the cells of an adult to mutate. This type of mutation may result in a disease such as cancer, but it will not be passed on to their offspring. In order for a mutation to be passed on to the offspring, the mutation had to be present in one of the parents’ gametes or the mutation occurred during conception.
For an episode synopsis of Teenage Mutant Ninja Turtles and questions which probe this misconception, go to http://www.life.uiuc.edu/bio100/lectures/s97lects/15Mutations/tmnt.html
.
For further information on this type of student misconception, visit http://www.indiana.edu/~oso/animations/An10.html
.

Content Benchmark L.8.A.2
Students know changes in genes of eggs and sperm can cause changes in inherited characteristics. E/S
Sample Test Questions
1.
The cells involved in sexual reproduction are known as a.
Somatic b.
Gametes c.
Alleles d.
Homologous
2.
Substances that cause mutations are known as a.
Agents b.
Operons c.
Mutants d.
Mutagens
3.
In order for a mutation to be passed from one generation to the next, the mutation must be present in which of the following cells? a.
Skin cell b.
Muscle cell c.
Heart cell d.
Sperm cell
4.
An example of a disorder caused by inheriting an extra #21 chromosome is a.
Down Syndrome b.
Tay Sachs c.
Sickle Cell Anemia d.
Color Blindness
5.
DNA sequence: AATGGCT ATGGCT
What type of mutation occurred to the DNA sequence above? a.
Translocation b.
Insertion c.
Frameshift d.
Inversion

Content Benchmark L.8.A.2
Students know changes in genes of eggs and sperm can cause changes in inherited characteristics. E/S
Answers to Sample Test Questions
1.
(b)
2.
(d)
3.
(d)
4.
(a)
5.
(c)

Content Benchmark L.8.A.2
Students know changes in genes of eggs and sperm can cause changes in inherited characteristics. E/S
Intervention Strategies and Resources
The following is a list of intervention strategies and resources that will facilitate student understanding of this benchmark.
1.
Slooze Worm Mutagenesis
This is an activity from the Genetic Science Learning Center where students determine how much of the Slooze Worm’s DNA has been mutated from living in the polluted waters of
Lake Abestozene.
Access this activity at http://learn.genetics.utah.edu/units/disorders/sloozeworm/scenario.cfm
2.
Mighty Mutation Maker
The Mighty Mutation Maker is an online game developed by nature.ca where students can decode their names into a sequence of codons. Next, the student selects a type of mutation which their name will undergo. The student can select and witness the effects of insertion, deletion, silent, missense, and nonsense mutations.
This educational resource is available at http://www.nature.ca/genome/04/0413_e.cfm
3.
Animated Demonstration of Mutations Accumulating Over Time
The following link takes you to the Indiana University Animation website. The site is designed to assist in student understanding of the effects of genetic mutations over many generations. One animation focuses on the evolution of whales and hippos, the other shows an example of human and chimpanzee evolution.
Access this animation at, http://www.indiana.edu/~oso/animations/An10.html
4.
A Mutation Story Video
A Mutation Story is an online video segment (4 minutes 50 seconds) from the PBS Evolution series. The video focuses on the mutation which causes sickle cell anemia. Although sickle cell anemia can be a deadly disease, the mutation has lead to survival benefits through a resistance to malaria. The video highlights a family in West Africa where both parents are carriers of sickle cell anemia and the effects it has on their offspring.
The video segment is available at http://www.pbs.org/wgbh/evolution/library/01/2/l_012_02.html

5.
Cracking the Code of Life Video
Cracking the Code of Life is a two-hour video that is divided into specific segments and available through NOVA Online. Chapter 3 (8 minutes 57 seconds) of the video entitled One
Wrong Letter tells the story of two couples who discover their child has Tay-Sachs disease, which is an incurable disorder caused by the misspelling of just one letter out of three billion in the entire human genome.
Use the following link to access the video http://www.pbs.org/wgbh/nova/genome/program.html
6.
University of Utah’s Genetic Science Learning Center
This link provides detailed information about the cause of mutations. It contains diagrams that illustrate mutations induced by environmental conditions and mutations caused by errors in the reading of the DNA.
The background information is available at http://learn.genetics.utah.edu/units/disorders/sloozeworm/mutationbg.cfm
7.
Berkeley Understanding Evolution: DNA and Mutations
This website integrates the types of mutations, the causes and effects of mutations, and a case study involving mutations. Links are also available to explain several pieces of evidence, including mutations that relate to how organisms have changed over time.
To reach the Berkeley website, use the following link http://evolution.berkeley.edu/evolibrary/article/mutations_01
8.
A Whale of a Change
This activity combines the concepts of mutations, inherited characteristics and evolution through the construction of an origami whale.
To access the directions for Whale of a Change go to http://www.lpb.org/education/classroom/ntti/cdpdf/12twhale.pdf