Biology 100/101
Lecture 15
Mutations
(Print Version)

Announcements

Objectives

Web Resources

What are Mutations?

Types of Mutations

Effects on Proteins

Word Analogies

Lecture Activity

Causes of Mutations

Somatic/Germinal Mutations

Not All Bad

Lecture Syllabus

IB 100/101 Home Page

Answers to many of these questions can be found at the Text On-Line Learning Center

You may also ask questions and see answers to your classmates' questions in Web Crossing in the "Talk to Jim, Ross, and Ed" discussion.

Objectives:

The content of today's lecture will help you answer question #2 on this assignment:

Take-home Assignment #6, Gene Expression and Mutation Due At Lecture Tuesday April 4

After studying this material you should be able to:

1. Define the term mutation.
2. Describe the types of mutations that can occur in a gene and the effect, if any, they have on the protein that is produced when the gene is expressed.
3. Describe how a mutation might occur by distinguishing between spontaneous and induced mutations.
4. Distinguish between somatic and germinal mutations and describe the consequences of each for a person's child.
5. Explain why mutations are not all harmful.
6. Understand these terms:

induced mutation	spontaneous mutation	germinal mutation
somatic mutation	missense mutation	nonsense mutation
frameshift mutation	mutagen	silent mutation

Web Resources:

• Genes and Disease (Selected genes and their functions and locations on the chromosomes) from the National Center for Biotechnology Information.
• The Beauty of Mutations from Access Excellence. This is a good read; have a look at it!
• Mechanisms of Antibiotic Resistance in Bacteria
• Battle of the bugs: Fighting Antibiotic Resistance. Bacteria develop resistance to certain drugs spontaneously through mutation.
• More on antibiotic resistance, from P&S Medical Review. Bacterial antibiotic resistance can develop as a result of a chromosomal mutation.

What are Mutations?

General Types of Mutations

• Changes in chromosome structure
• Deletion, duplication, inversion, or translocation.

• Changes in chromosome number
• Polyploidy, aneuploidy (autosomes or sex chromosomes). Review Lecture 12, Chromosomes and Traits.

• Changes made by substituting a single base with another or by adding or deleting one or more nucleotides.
• Sickle cell disease results from a single base change (See Figure 13.17, in Lewis et al., page 256)
  Remember! In RNA, the nucleotide base uracil replaces thymine.

Genetic Mutations and their Effects on Proteins

• Transcription DNA --> RNA
• Chose "Copying the Code" toward the bottom of the screen
• then select "puting it together" from the top of the next screen.
• Then choose the "Transcription animation"

• Translation mRNA --> Protein
• Chose "Reading the Code" toward the bottom of the screen
• then select "puting it together" from the top of the next screen.
• Then choose the "Translation animation"

• A missense mutation substitutes a different amino acid for the original one.

Example: Sickle cell disease results from a single base change (See Figure 13.17, in Lewis et al., page 256)
Remember! In RNA, the nucleotide base uracil replaces thymine.

TEMPLATE DNA code CTC (Glutamine - glu) -mutation->
TEMPLATE DNA code CAC (valine - val)

• A nonsense mutation results in a stop codon being inserted someplace before the end of the gene.

TEMPLATE DNA code ATG (tyrosine - tyr) -mutation->
TEMPLATE DNA code ATT (STOP)

• Silent mutations are point mutations that do not change the amino acid sequence of the protein. These are most likely to have no effect. Redundancy of the Genetic Code reduces the chance that point mutations do not alter the specified amino acids.

The mRNA codons GAA and GAG code for the amino acid Glutamic Acid (Glu).
The mRNA codons GCU, GCC, GCA, and GCG all code for the amino acid Alanine (Ala).
The mRNA codons GGU, GGC, GGA, and GGG all code for the amino acid Glycine (Gly).

• Frameshift Mutations: Additions or deletions of one or more nucleotides.
• May result in "garbage" genes, as the entire amino acid sequence in the code after the change is devastated.
• Large deletions may remove a single amino acid, or an entire chunk of chromosome. The most common mutation that causes severe cystic fibrosis deletes only a single codon.
• Real examples of missense, nonsense, and frameshift mutations:

Hemoglobin mutants and Hemoglobin molecule

A note of caution. These examples show the NON-template DNA sequence rather than the template DNA sequence as in our previous examples. This is a standard used by DNA scientists. To get the mRNA codons, just change the Ts to Us.

• Some genes have repeated base sequences, and the number of these may increase each generation. These expanding genes are responsible for increasingly severe cases of muscular dystrophy (CTG repeats), Huntington disease (CAG repeats), and Fragile X syndrome (CGG repeats).

Fragile X Syndrome:
6-50 CGG repeats in an unaffected individual
50-200 CGG repeats in a carrier
>200 CGG repeats in an affected individual

Word Analogies for Types of Mutations

Mutation Lecture Activity

mRNA Code Chart

• Point mutations - changes in single DNA nucleotides.

  Part of gene to be transcribed	CTG / TTA / CGC
  Mutation 1	CTG / TTG / CGC	Silent
  Mutation 2	CTG / TTT / CGC	Missense
  Mutation 3	ATT / TTA / CGC	Nonsense

  What is the mRNA sequence without mutation?
  With mutation 1, 2, and 3?

  What is the amino acid sequence without mutation?
  With mutations 1, 2, and 3?

• Frameshift mutations: Additions or Deletions of one or more nucleotides.

  Part of gene to be transcribed	CTG / TTA / CGC
  Mutation 1	CTA / GTT / ACG / C	Addition
  Mutation 2	CT_T / TAC / GC	Deletion
  Mutation 3	CTG / CTG / TTA / CGC	Expansion

  What is the mRNA sequence without mutation?
  With mutation 1, 2, and 3?

  What is the amino acid sequence without mutation?
  With mutations 1, 2, and 3?

  Mutation Lecture Activity Summary (Click Here to See Answers)

Causes of Mutations

• Damage may occur at any time in any cell. Mutations result when the damaged genes are replicated without repairing them first. Chromosome replication is 99.999% accurate. Errors in the actual duplication process happen only about once in 100,000 bases. Given that the human genome has about 6 billion bases, this means each replication cycle will have 60,000 errors associated with it. However, cells contain several complex systems to fix damage before, during, and after DNA replication.
• Some genes mutate at a higher rate than others.
• Such mutations occur more frequently in organisms with very short generation times, such as viruses and bacteria.

• DNA sequences are altered as a result of exposure to mutagens (agents that increase the rate of mutation).
• Mutations may be purposely induced for research purposes (chemicals, gamma rays, x-rays). Natural mutagens include radon, cosmic rays, and UV light. Human-created mutagens include pollution, pesticides, chemicals, nuclear testing and accidents, and biological warfare. Also, exposure in utero to alcohol, cocaine, carbon monoxide, German measles, lead, mercury, and many others.
• Watch out for Worcester Sauce!
• A Definition of carcinogen
• A current list of known carcinogens
• What's the #1 Carcinogen???
• Been to the Art Institute in Chicago??
• An introduction to skin cancer. UV light is a mutagen. The sunburn you receive this week may take 20 years or more to become skin cancer. Think about this before hitting the beaches or the tanning salon.

Somatic Mutations vs. Germinal Mutations

Somatic Mutations (Greek Soma= body)

• Mutations in the body cells of an organism, including any cell type EXCEPT the cell lines destined to produce eggs or sperms by meiosis.
• Somatic mutations early in development may affect the entire development process of the organism, or may result in the cells of an individual not being entirely genetically uniform.
• Somatic mutations may result in unusual cell growth (such as cancer).

Germinal Mutations (Latin germinare= to sprout)

• Mutations in cells destined to produce gametes (eggs and sperm).
• Germinal mutations result in genetically altered gametes that may be passed on to the individual's offspring. This means that these mutations may not affect the individuals in which they occur, but may result in genetic disorders in their offspring.

Were these deformities the result of a somatic or germinal mutation?

Mutations are Not All Bad

• Mutations may occur in non-coding regions of DNA.
• The amount of DNA you have is much greater than that accounted for by your genes. Even with 31,000+ protein-encoding genes and a daily production rate of billions of protein molecules, the vast majority of your DNA is not involved in protein coding.
• Even within an allele, as much as 95% of the DNA is non-coding. Introns get spliced out before protein synthesis starts.
• Mutations in non-coding regions usually do nothing to the phenotype of the individual.
• Even within coding regions of alleles, some types of mutations have no effect on the resulting protein.

• Mutations do much more than cause genetic disorders or cancers. They do not occur only in humans.
• Mutations increase the genetic variability of a population. They are a way to introduce new alleles into a population.
• An allele is an alternate form of a gene. Alleles are formed by mutations of pre-existing alleles. For some genes, there may be hundreds of different alleles.
• Genetic variability is essential to the survival of a species and even the formation of new species.
• Mutations make evolution possible.