DNA Mutations Biology 6(E)

DNA Mutations Learning Objectives Identify and describe types of mutations that can occur in DNA Evaluate how DNA mutations affect protein synthesis and the survival of organisms After this lesson you will be able to identify and describe types of mutations that can occur in DNA. You will also be able to evaluate how DNA mutations affect protein synthesis and the survival of organisms.

DNA Mutations Mutation – a random change in the sequence of a gene ATCGA TAGCT ATCAA Caused by: Mistakes in DNA replication process Environmental agents that damage DNA A mutation is a random change in the sequence of a gene. Mutations have two primary causes. The first cause is a mistake that occurs during the DNA replication process. Although cells have mechanisms in place to double-check the new DNA strands created during DNA replication, errors can still occur. In the top image, an incorrect base has been added to one of the new DNA strands. The second cause of DNA mutations are environmental agents, such as ultraviolet radiation and chemical toxins. These environmental agents can damage existing DNA, leading to mutations. In the bottom image, ultraviolet radiation has damaged a group of bases on one of the DNA strands, causing the bases to pair with each other instead of with their complementary bases on the other DNA strand.

Types of DNA Mutations Point mutation/Substitution Inversion Insertion Deletion Translocation C T C G A T A Five major types of mutations occur in DNA: point mutations, or substitutions, inversions, insertions, deletions and translocations. Let’s look at each of these types of mutations in more detail. When we look at these examples, we will be using an illustration of bases. Remember that there are only four bases, generally abbreviated A, T, G, and C. To illustrate the changes more easily, we will use an illustration with seven bases named A through G. These bases could actually correlate to any base sequence.

Types of DNA Mutations Point mutation/Substitution – one base replaced with another base Inversion – order of two or more bases is reversed A point mutation, or substitution, occurs when one nucleotide base is replaced with another base. In the example, base C has been replaced with base Z. An inversion occurs when the order of two or more nucleotide bases is reversed. In the example, bases CDE have been inverted to EDC.

Types of DNA Mutations Insertion – addition of one or more new bases Deletion – removal of one or more bases An insertion occurs when one or more new nucleotide bases are added to a DNA sequence. In the example, an extra base Z has been added between bases E and F. A deletion occurs when one or more nucleotide bases are removed from a DNA sequence. In the example, bases CD have been removed from the original sequence.

Types of DNA Mutations Translocation – movement of one or more bases to a new location in a different DNA sequence A translocation occurs when one or more nucleotide bases are moved to a new location in a different DNA sequence. In the example, bases CDEFG from the top strand have switched places with bases EFG from the bottom strand.

DNA to Proteins Transcription – mRNA created from DNA template Sequence of nucleotide bases is identical, except for replacement of thymine (T) with uracil (U) Translation – protein created from mRNA template Each three-base mRNA codon translates to a single amino acid …TACGTGCACGTTCTG… …ATGCACGTGCAAGAC… …UACGUGCACGUUCUG… Tyr-Val-His-Val-Leu DNA (transcription) RNA (translation) Protein To understand the significance of these types of DNA mutations, let’s briefly review the process of going from a DNA sequence to a functional protein. First, an mRNA transcript of the DNA sequence is made during the process of transcription. The sequence of nucleotide bases in mRNA is an exact copy of one of the original DNA sequences, with the exception of the use of uracil in mRNA in place of thymine. The mRNA transcript is then used as a template to build proteins during the process of translation. Remember that mRNA is read in three-base segments called codons. Each codon corresponds to a particular amino acid that will be added to the protein chain.

DNA to Proteins The genetic code determines which amino acid will be used During translation, the genetic code determines which amino acid will be used. You can see here that changing the codon will often result in a different amino acid.

DNA Mutations Changes in sequence of a gene can cause changes to the protein that is produced during translation Can affect proteins produced in different ways: Silent mutations Missense mutations Nonsense mutations Frameshift mutations Remember that the mRNA template used during translation is created using the original DNA sequence. This means that any changes in the sequence of a gene can cause changes to the protein that is produced from that gene. Each type of mutation that we have discussed changes the protein produced in different ways. These mutations can be described as silent, missense, nonsense or frameshifts depending on their specific effect on a protein. Let’s take a look at each of these in more detail.

Silent Mutations Silent mutation – mutation that causes no change in amino acid sequence Genetic code has redundancies Caused by point mutations …TACAACCTCACC… …ATGTTGGAGTGG… …AUGUUGGAGUGG… Met-Leu-Glu-Trp… DNA (transcription) RNA (translation) Protein …TACAATCTCACC… …ATGTTAGAGTGG… …AUGUUAGAGUGG… A silent mutation causes no change in the amino acid sequence of a protein. This is a result of redundancies in the genetic code. For example, both the codons UUA and UUG encode for leucine. Because of these redundancies, point mutations can be silent mutations. In the example, a point mutation has occurred in the DNA that will be used for the second codon. A cytosine base is replaced with a thymine base in the mutant DNA strand. The resulting mutant mRNA codon, UUA, happens to code for the same amino acid (leucine) as the original mRNA codon. Since no change occurs in the amino acid sequence, the protein produced is unaffected by the mutation.

Missense Mutations Missense mutation – mutation that changes the identity of an amino acid added Most often because of point mutations May be because of inversions …TACAACCTAACC… …ATGTTGGATTGG… …AUGUUGGAUUGG… Met-Leu-Asp-Trp… DNA (transcription) RNA (translation) Protein …TACAACCTCACC… …ATGTTGGAGTGG… …AUGUUGGAGUGG… Met-Leu-Glu-Trp… A missense mutation changes the identity of an amino acid added to a protein chain. While many groups of codons code for the amino acid, there are instances where changing a base changes the amino acid. Most missense mutations are point mutations, though they can also result from inversions. In the example, a point mutation has occurred. An adenine base is replaced with a cytosine base in the mutant DNA strand. The resulting mutant mRNA codon codes for a different amino acid than the original mRNA codon. This changes the identity of an amino acid in the chain, which could change the identity or properties of the protein produced.

Nonsense Mutations Nonsense mutations – mutation that shortens a protein by replacing an amino acid codon with a stop codon Most often because of point mutations Large impact on protein produced …TACAACATGACC… …ATGTTGTACTGG… …AUGUUGUACUGG… Met-Phen-Tyr-Trp… DNA (transcription) RNA (translation) Protein …TACAACATCACC… …ATGTTGTAGTGG… …AUGUUGUAGUGG… Met-Phen-STOP A nonsense mutation shortens a protein by replacing a codon for an amino acid with a stop codon. Nonsense mutations are the result of point mutations. In the example, a point mutation has occurred. A guanine base was replaced with a cytosine base in the mutant DNA strand. The resulting mutant mRNA codon signals translation to stop rather than adding the next amino acid in the chain. This change shortens the protein produced, which can severely limit its function.

Frameshift Mutations Frameshift mutation – mutation that alters the reading frame in which codons are translated Caused by insertions, deletions, and translocations Large impact on protein produced …TACAACATGACCCTA… …ATGTTGTACTGGGAT… …AUGUUGUAUUGGGAU… Met-Leu-Tyr-Trp-Asp… DNA (transcription) RNA (translation) Protein …TACAACTATGACCCTA… …ATGTTGATACTGGGAT… …AUGUUGAUAUUGGGAU… Met-Leu-Ile-Leu-Gly… A frameshift mutation alters the reading frame in which mRNA codons are read. Frameshift mutations occur when the total number of bases is changed. This can be caused by insertions, deletions, or translocations. In the example, an insertion has occurred. A thymine base has been added at the seventh base location in the mutant DNA sequence. The addition of an extra base shifts the reading frame by one base. This causes all mRNA codons after the insertion to be read incorrectly. Starting at the third base, the protein produced is composed of a completely different chain of amino acids than was intended by the original sequence. As you can see, frameshift mutations can have a large impact on the protein produced.

DNA Mutations and Survival Mutations can be organized by their effect Neutral mutations – no effect on organism’s survival Increase genetic diversity in a species Example: human eye color Harmful mutations – decrease organism’s survival Produce genetic disorders or unfavorable traits Example: cancers Beneficial mutations – increase organism’s survival Produce favorable traits Example: antibiotic resistance in bacteria Remember that proteins are responsible for directing the functions of an organism’s cells. A DNA mutation that alters the identity or function of a protein can impact an organism’s survival in three possible ways. Neutral mutations have no effect on an organism’s survival. An example would be a mutation that causes variations in the eye color of humans. Since these mutations do not help or hurt the organism, they tend to increase genetic diversity within a species because natural selection does not favor or work against them. Harmful mutations decrease chances of survival by producing genetic disorders or unfavorable traits in an organism. An example of a harmful mutation would be one that leads to the development of cancer cells. An organism with this mutation would be less likely to survive and reproduce. Beneficial mutations increase chances of survival by producing favorable traits in an organism. An example of a beneficial mutation would be one that leads to antibiotic resistance in bacteria. Bacteria with this mutation would be more likely to survive and reproduce.

DNA Mutations Learning Objectives Identify and describe types of mutations that can occur in DNA Evaluate how DNA mutations affect protein synthesis and the survival of organisms You should now be able to identify and describe types of mutations that can occur in DNA. You should also be able to evaluate how DNA mutations affect protein synthesis and the survival of organisms.