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As you have learned, the specific sequence of nucleotides in DNA is critical in each step that leads to the end product of a gene. However, there are many opportunities for errors and mistakes. These changes in the DNA sequence are called mutations. Mutations can happen in any of the stages previously discussed and can range from single nucleotide changes to long segment insertions or deletions. Some of these mutations will be repaired and others will lead to changes that will be passed on to the next generation. In this section, we will discuss different types of mutations as well as their potential effects.
Types of DNA Damage
After DNA has been completely replicated, the daughter strand is often not a perfect copy of the parent strand it came from. Mutations during replication and damage after replication make it necessary for there to be a repair system to fix any errors in newly synthesized DNA. There are many sources of damage to DNA including the loss of a nucleotide, chemical damage that alters the DNA structure, and radiation which breaks bonds in the DNA that may not reform correctly.
Repair Systems
Because the types and causes of DNA damage are different, there is a need for multiple repair systems.
The first type of repair system we will discuss is the excision repair system. To excise simply means to remove, so this repair systems works by removing the area of damage. Special enzymes recognize damaged DNA. These sections are then removed, the gap is filled with DNA polymerase, and the nick is sealed by a DNA ligase. This repair system comes in two forms: Base-excision repair and short-patch nucleotide excision.
The other major type of repair system corrects damage resulting from mismatched bases, called the mismatch repair system. The mismatch repair system is able to identify mismatch errors because such damage leads to a small distortion in the DNA backbone. Once it has identified a mismatched base pair, it marks the spot with a cut and uses an exonuclease to digest or "eat up" the DNA at the marker. A DNA polymerase can then fill in the gap with the appropriate base.
Sometimes, mutations are not repaired. If not, these changes are passed on and affect translation of the genetic material into a protein.
Mutations Effect on Translation
Some mutations in DNA or RNA may not have much effect. For example, if the codon GAA becomes the codon GAG, because the genetic code is degenerate, the codon will still code for the amino acid glutamate. Such ineffectual mutations are called silent mutations. Some mutations, however, can have a huge impact on coding for amino acids, which can in turn affect what proteins are produced, which can ultimately have a profound effect on cellular and organismal function.
The most common mutations occur in two ways: 1) a base substitution, in which one base is substituted for another; 2) an insertion or deletion, in which a base is either incorrectly inserted or deleted from a codon.
Base Substitutions Mutations
Base substitutions can have a variety of effects. The silent mutation cited above is an example of a base substitution, where the change in nucleotide base has no outward effect. A missense mutation refers to a base substitution when the change in nucleotide changes the amino acid coded for by the affected codon. A nonsense mutation refers to a base substitution in which the changed nucleotide transforms the codon into a stop codon. Such a change leads to a premature termination of translation, which can badly affect the formation of proteins.
Insertion/Deletion Mutations
When a nucleotide is wrongly inserted or deleted from a codon, the effects can be drastic. Called a frameshift mutation, an insertion or deletion can affect every codon in a particular genetic sequence by throwing the entire three by three codon structure out of whack. For example, given the code:
GAU GAC UCC GCU AGG, which codes for the amino acids aspartate, aspartate, serine, alanine, arginine.
If the A in the GAU were to be deleted, the code would become: GUG ACU CCG UAG G
In other words, every single codon would code for a new amino acid, resulting in completely different proteins coded for during translation. The physical results of such mutations are, understandably, usually catastrophic. However, sometimes these mutations can be beneficial.
Genetic Variation and Natural Selection
Mutations are the primary source of genetic variation. Genetic variation can lead to changes in phenotype, or the observable traits of an organism. These changes may make an organism more or less likely to survive, reproduce, and pass on the mutation. This process is called natural selection and will be discussed more in Unit 7. Genetic variation may also occur from the transfer of DNA from other sources. Some key processes that facilitate this are transformation, transduction, conjugation, and transposition. Collectively, these are referred to as horizontal gene transfer. Transformation occurs most commonly in prokaryotes. Prokaryotes will uptake DNA from their environment and integrate it into their genome via transformation. Transduction occurs when viruses insert DNA into cells that they infect. Since viruses carry DNA within them, they have the ability to introduce this genetic variation to other cells. Conjugation is the cell-to-cell transfer of DNA between bacterial cells. Usually, the DNA is in the form of a plasmid that passes through a structure called the pilus. This requires direct cell-to-cell contact. Transposition is the movement of DNA segments within and between DNA molecules. The DNA segments are called transposons and their movement can alter gene expression and create genetic variation.
Errors in Mitosis and Meiosis
While we have primarily focused on small mutations within a single gene or chromosome, errors in mitosis or meiosis can occur that lead to changes in chromosome number. These changes have an ultimate effect on the organism’s phenotype. One example is triploidy; here an organism has three sets of chromosomes instead of two. This usually results in sterility and the inability to produce offspring due to the challenge of pairing chromosomes during meiosis. However, in other instances, if there are multiple sets of chromosomes (a condition called polyploidy) an organism may increase in size or vigor. This happens most frequently in plants.
In humans, changes in chromosome number often result in disorders that have alterations in developmental processes. Two common examples are Down syndrome and Turner syndrome. Individuals with Down syndrome, also called Trisomy 21, have an extra copy of chromosome 21. This disrupts normal development and leads to characteristic physical features, intellectual differences, and other health issues. Females with Turner syndrome only have one X chromosome instead of two. This can lead to infertility, short stature, and other physical differences. These are just some of the examples of phenotypic differences that can occur from errors during cell division.
