Biology 100/101
Lecture 15
Mutations
(Print Version)

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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
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Text Readings in Lewis et al.

Chapter 13, Gene Function, pp. 249-252

The "Reviewing Concepts" boxes are valuable summaries of the main ideas in these sections of the text.

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Web Crossing

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

Objectives:

The content of today's lecture will help you answer the questions on these assignments:

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:

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

Web Resources:

What are Mutations?

  • A mutation is any physical change in the genetic material (such as a gene or a chromosome). A gene that contains a mutation (a change in the base sequence of the DNA) will produce an altered mRNA molecule that will produce an altered sequence of amino acids in the resulting protein.

  • More than 4,000 diseases are thought to stem from mutated genes inherited from our parents.

  • A mutation may or may not affect the amino acid sequence.

  • A mutation may or may not affect the phenotype.

  • Some specific mutations in a gene may have more adverse affects than other mutations in the same gene.

  • A mutation is not necessarily bad. It may even be good. A mutation may enhance or positively change the function of the protein produced by the gene.

    • General Types of Mutations

  • Chromosomal Mutations

  • Point Mutations

    • Changes in the DNA of a gene made by the substitution of a single base with another or by addition or deletion of one or more nucleotides.

    Genetic Mutations and their Effects on Proteins

  • A Review of Protein Synthesis, by Access Excellence.

  • Protein Synthesis from DNA Interactive
    • 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"

  • Gene Expression via Protein Synthesis, from Access Excellence. For a cell to make protein, the information from a gene is copied, base by base, from DNA into new strands of messenger RNA (mRNA). Then mRNA travels out of the nucleus into the cytoplasm, to cell organelles called ribosomes. There, mRNA directs the assembly of amino acids that fold into a completed protein molecule.

  • How are genes linked to disease? When a gene contains a mutation, the protein encoded by that gene may well be abnormal.

  • There are many ways that mutations can occur and affect gene expression. To understand them, you need to familiarize yourself with the use of the Genetic Code. The same Code is found in the text, table 13.1, pg. 246

  • THE GENETIC CODE CHART USES THE CODONS IN THE mRNA!!!!!!

  • Point Mutations: Changes in single DNA nucleotides.

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

    • 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 that result in a change in the third nucleotide of a codon will alter the specified amino acid.

        • 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.

      • Ribosomes decode mRNA three nucleotides (one codon) at a time. Translation starts at the initiator sequence (AUG) and continues with the next three nucleotides, then the next three, and the next three, etc. Ribosomes have a "reading frame" that decodes sets of three nucleotides, or codons. There are no "punctuation marks" to delineate the codons, so adding or deleting one or more nucleotides in the DNA changes the "reading frame" of the codon sequence of the mRNA produced from that point in the allele.

      • The amino acid sequence in the protein from that point will all be changed, radically changing the shape and function of the protein.

      • Adding or deleting triplets (three or multiples of three nucleotides) will add or delete one or more amino acids.

        • If the triplet(s) is/are added or deleted between two codons, there will be no disruption of the reading frame and all other amino acids in the protein will remain unchanged.

        • If the triplet(s) is/are are added or deleted within a codon, there will be a temporary disruption of the reading frame, but the reading frame will quickly get back on track. One or two neighboring amino acids might be changed with the addition or deletion, but all other amino acids in the protein will remain unchanged.

  • Real examples of missense, nonsense, and frameshift mutations:

      • Mutants of Hemoglobin (From Dr. Robert J. Huskey)

      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.

  • Expanding Genes - Some genes have repeated base sequences, and the number of these may increase each generation. Expanding genes are responsible for increasingly severe cases of myotonic muscular dystrophy (AGC/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

    The concept of expanding genes is the foundation of the current method of DNA profiling ( DNA fingerprinting). (To be addressed in Lecture #19)

    Word Analogies for Types of Mutations

  • Table 13.4 (text, p. 260) uses a sentence of three-letter words as an analogy to demonstrate the effects of mutations on gene sequence.

    • Wild type
    "Normal Gene"    		 THE ONE BIG FLY HAD ONE RED EYE
    Missense THQ ONE BIG FLY HAD ONE RED EYE
    Nonsense THE ONE BIG
    Frameshift THE ONE QBI GFL YHA DON ERE DEY
    Deletion THE ONE BIG HAD ONE RED EYE
    Duplication THE ONE BIG FLY FLY HAD ONE RED EYE
    Insertion THE ONE BIG WET FLY HAD ONE RED EYE
    Expanding (P) THE ONE BIG FLY HAD ONE RED EYE
    Expanding (F1) THE ONE BIG FLY FLY FLY HAD ONE RED EYE
    Expanding (F2) THE ONE BIG FLY FLY FLY FLY FLY FLY HAD ONE RED EYE

    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

  • Spontaneous 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.

  • Induced Mutations

    • 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 can NOT be passed on to one's children.

    • Mosaicism - Somatic mutations that occur early in development may affect all the cells of the organism, or may result in the cells of an individual not being entirely genetically uniform. Some parts of the body that develop from cells in the embryo that are mutated will be affected by the mutation. Parts of the body developed from normal cells will be normal. This condition is called "Mosaicism". Mosaicism may occur with anuploid situations as well.

    • 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 25,000+ 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 and Evolution.

      • 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.

      • Some mutations actually increase the efficiency of the protein produced or may change its function (remember antibiotic resistant bacteria?).

      • Genetic variability is essential to the survival of a species and even the formation of new species.

      • Mutations make evolution possible.