Mutations and Genetic Variation

What is a mutation?

• Random Changes in the DNA sequence. 

• Mutations can have variable effects on an organism, depending on the severity/ type of mutation. 

• Most mutations have NO EFFECT on an organism.

• Negative and positive mutations are very, very rare.

mRNA Reading Frame

• Reading frame refers to the sequence of nucleotides that actually codes for protein and is “read” by the ribosome 

• Beginning- Start Codon

• End- Stop Codon

• Any mutations to the reading frame sequence can cause a change in protein structure, which can prevent the protein from functioning. 

• mRNA strands frequently have multiple reading frames

  • Another way to allow for multiple proteins to be made from one gene sequence 

The Central Dogma of Biology

• DNA-->RNA-->Protein

• Mutations can cause changes in the mRNA sequence, which may change the amino acid sequence of the protein and stop the protein from working correctly. 

• Proteins that do not work will cause a change in the phenotype, or physical expression of the trait.

• Sometimes this leads to disease.

Point Mutation

-Usually a change in 1 to 3 nucleotides and only affect one gene. 

-Point mutations occur during DNA Synthesis in the Cell Cycle.

• Point mutations are chemical changes in just one base pair of a gene.

• The change of a single nucleotide in a DNA strand can lead to the production of an abnormal protein.

• Point mutations can be divided into two general categories:

  • Base-pair substitutions and base-pair insertions or deletions

Chromosomal Mutation

-Chromosomal mutations occur during meiosis. 

-Mutations that affect big sections of chromosomes and affect many genes. 

Mutation Subtypes

Base-Pair Substitutions

A base-pair substitution replaces one nucleotide and its partner with another pair of nucleotides.

• They can cause synonymous(Silent), missense, or nonsense mutations.

  • A synonymous mutation still codes for the same amino acid (example of a silent mutation).

  • Missense mutations still code for an amino acid, but not the correct one.

  • Nonsense mutations change an amino acid codon into a stop codon, nearly always leading to a nonfunctional protein

Silent Substitution Mutation

• A change in a single nucleotide that doesn’t result in a change in amino acid sequence. 

• No effect on protein structure or function.

• No change in the phenotype of the organism. 

Missense Mutation

• A change in a single nucleotide that results in a change in a single amino acid in the sequence. 

• Variable effect on protein function and phenotype of the organism. 

Variable Effects of Missense Mutations

• Protein stops working entirely

  • Mutations that cause amino acids with completely different chemical properties to be incorporated into the activate site of a protein. 

• Decreased functionality of the protein

  • Mutations that cause amino acids with similar chemical properties to be incorporated into the active site of the protein. 

• Increased or new function of the protein (very rare)

  • Mutation causes a change in amino acid sequence that allows the protein to be more functional and/or gain a completely new function leading to a new phenotype. 

Nonsense Mutation

• A change in a single nucleotide that results in a premature stop-codon in the mRNA sequence.

• Negative impact on protein structure and function

  • Codons after stop codon will not be translated

  • Protein will not have all of its amino acids, so it won’t fold or function properly. 

Base-Pair Insertions and Deletions

• Insertions and deletions are additions or losses of nucleotide pairs in a gene

• These mutations have a disastrous effect on the resulting protein more often than substitutions do.

• Insertion or deletion of nucleotides may alter the reading frame, producing a frameshift mutation.

  • A frameshift mutation changes all of the codons translated after the point of mutation, and thus changes all the corresponding amino acids. 

Insertion Mutation

• Insertion of a single nucleotide into the DNA sequence.

• Insertions change  the reading frame which also changes the entire amino acid sequence after the insertion.

• Protein will not fold or function correctly

Deletion Mutation

• Deletion of a single nucleotide into the DNA sequence.

• Deletions change  the reading frame which also changes the entire amino acid sequence after the deletion.

• Protein will not fold or function correctly

Mutagens

• Spontaneous mutations occur with no outside influence. This could be a result of replication errors by DNA polymerase—most are repaired but some become permanent.

• Mutagens, however, are physical or chemical agents that can cause mutations.

• Examples of mutagens include:

  • Radiation (such as X-rays or ultraviolet radiation from the sun) 

  • Harmful chemicals (such as some bromine, benzene, and nitrous acid). 

  • Mutagens are also found in the chemical defenses of some plants and fungi.

Effects of Mutations

• Mutations can have benefits:

  • Provides the raw material for evolution in the form of genetic diversity

  • Diversity may benefit the organism immediately—if mutation is in somatic cells

  • Mutations in germ line cells may cause an advantageous change in offspring

• Mutations can be harmful if they result in loss of function of genes or other DNA sequences needed for survival.

  • Harmful mutations in germ line cells can be passed to offspring.

  • Harmful mutations in somatic cells can lead to cancer.

• Mutations can have no effect (silent) if they have no effect on a protein.

  • Either the changed codon encodes the same amino acid, or the mutation occurred in a noncoding segment of DNA (DNA that is not part of a gene).

Processes that Increase Genetic Variation
-Mutations are the ultimate source of genetic variation and create genetic variation in ALL life on earth (both prokaryotic and eukaryotic).

• Along with mutations, there are many other processes that can allow organisms and species to acquire new combinations of DNA, leading to new genetic variation.

  • In eukaryotes: sexual reproduction (which includes the processes of segregation, independent assortment, crossing over, and fertilization)

  • In prokaryotes: horizontal gene transfer (which includes the processes of transformation, transduction, conjugation, and transposition).

  • In viruses: recombination between related viruses.

Genetic Variation in Eukaryotes

• Sexual reproduction in eukaryotic organisms is a huge source of genetic variation.

  • The segregation, independent assortment, and crossing over of alleles during gamete formation (meiosis) create incalculable combinations of DNA in the resulting sperm or egg cells… all of which were formed from the exact same starting DNA in the parent. 

  • Fertilization of a random egg cell by a random sperm cell from two parents results in a zygote with a new combination of DNA that has never existed.

Genetic Variation in Prokaryotes

• Prokaryotes reproduce asexually, which creates offspring that are genetic replicas of the parents.

• Prokaryotes, however, can gain genetic variation during their life through a process called horizontal gene transfer:

  • This is when an organism acquires genetic material from another organism that it is relatively unrelated to; as opposed to vertical gene transfer, which is the transmission of DNA from parent to offspring.

Genetic Variation in Prokaryotes-Transformation

• There are four processes that can be involved in horizontal gene transfer: transformation, transduction, conjugation, and transposition. All of these contribute to genetic variation in bacteria.

• Transformation occurs when a bacterial cell uptakes “naked” DNA, typically fragments or plasmids, from its surrounding (usually from a nearby lysed cell).

Genetic Variation in Prokaryotes-Transduction

• Transduction occurs when foreign bacterial DNA is introduced into a new bacterial cell by a bacteriophage (virus). 

  • When a bacteriophage infects a cell, it forces the cell to make copies of its genetic material and protein coat. The viral DNA is then loaded into the viral protein coats and are released from the cell.

  • During this process many viruses attack and fragment the bacteria’s DNA, preventing the bacteria from turning on defensive genes.

  • These bacterial DNA fragments can sometimes get loaded into the viral coats that are released by the cell, causing those viruses to carry bacterial DNA to future bacteria cells that they infect.

Genetic Variation in Prokaryotes-Conjugation

• Conjugation occurs when DNA - most commonly a plasmid - is transmitted between bacterial cells through direct contact. This requires the ability to form a connecting bridge structure called a pilus. 

  • Transformation and transduction do not require direct contact.

Genetic Variation in Prokaryotes-Transposition

• Transposition occurs when segments in a DNA molecule relocate to different positions in the same molecule or relocate to a different DNA molecule.

  • In bacteria cells, this commonly occurs between plasmids and the bacterial chromosome, allowing certain genes from the chromosomes to become part of a plasmid, and vice versa.