D1.3  Mutation and Gene Editing

Theme:  Continuity and Change

There is continuity of the genome despite constant exposure to mutagens and DNA replication errors.

• Many regions of the genome show extreme continuity over millions of years. This demonstrates that for essential life functions, natural selection favors the continuity of the original code.
  
• Due to the degeneracy of the genetic code, some base-pair changes do not alter the amino acid produced. These silent mutations maintain the biological function of the protein created.
  

Genome changes occur through both the natural occurrences of mutation and the deliberate gene-editing by humans.

• Mutations are a change to the DNA sequence and are the ultimate source of all genetic variation, providing the new alleles upon which natural selection acts.
  
• Environmental factors (UV light, radiation, chemicals) increase the rate of mutations. While often deleterious, mutations can occasionally lead to an advantageous trait.
  
• Gene editing technology such as CRISPR-Cas9 represents a paradigm shift in genetic change. Humans can now induce directed change to target a specific DNA sequence to correct genetic disorders or introduce new traits into a genome.
  

Guiding Questions:  
Guiding questions help students view the content of the syllabus through the conceptual lenses of both the themes and the levels of biological organization.

• How do gene mutations occur?
• What are the consequences of gene mutation?

​Linking Questions:  
Linking questions strengthen students’ understanding by making connections between topics.  The ideal outcome of the linking questions is networked knowledge.

• How does variation in subunit composition of polymers contribute to function?
• How can natural selection lead to both a reduction in variation and an increase in biological diversity?

Key Terms to Know: * higher level only

Amino Acid
Animal Model*
Base Substitution Mutation
Beneficial Mutation
Cancer
Cas9*
Conserved Sequence*
CRISPR*
Degeneracy (of Genetic Code)

Deletion Mutation
DNA Replication
Frameshift Mutation
Gene Editing*
Gene Knockout*
Gene Mutation
Genetic Variation
Genome
Germ Cell

Harmful Mutation
Highly Conserved Sequence*
Insertion Mutation
Mutagen
Neutral Mutation
Polypeptide
Radiation
Single Nucleotide Polymorphism
Somatic Cell

D1.3.1—  Gene mutations as structural changes to genes at the molecular level.

• Define mutation.
• Distinguish between base substitution, insertion and deletion mutations.​

D1.3.2-- Consequences of base substitutions.

• Define single- nucleotide polymorphism. 
• Compare the impact of base substitution mutation in coding and noncoding sequences of DNA.
• Outline the impact of genetic code degeneracy on the effect of mutations.
• Distinguish between same-sense, nonsense and mis-sense base substitution mutations.

D1.3.3-- Consequences of insertions and deletions.

• Define “frameshift” mutation.
• Outline the consequences of insertions and deletions on polypeptide structure and function.

D1.3.4-- Causes of gene mutation.

• Outline causes of gene mutation. 
• Define mutagen.​

D1.3.5— Randomness in mutation.

• Discuss the impact of randomness of gene mutations.
• State that no natural mechanism is known for making a deliberate change to a DNA sequence.​

​​​​D1.3.6-  Consequences of mutation in germ cells and somatic cells.

• Distinguish between germ cells and somatic cells. 
• Compare the consequences of a germ cell versus somatic cell mutation.

 ​​​​D1.3.7- Mutation as a source of genetic variation.

• Define genetic variation.
• State the source of new alleles of a gene.
• State that gene mutation is the original source of all genetic variation.
• Distinguish between beneficial, neutral and harmful gene mutations.

AHL ​​​​​D1.3.8-  Gene knockout as a technique for investigating the function of a gene by changing it to make it inoperative.

• State the function of gene knockout studies.
• Outline the method scientists use to “knockout” genes.

AHL ​​​​​D1.3.9-  Use of the CRISPR sequences and the enzyme Cas9 in gene editing.

• Describe the process of gene editing using CRISPR Cas9.
• Outline uses of CRISPR Cas9 gene editing.
• Outline the ethical implications of gene editing.

AHL ​​​​​D1.3.10- Hypotheses to account for conserved or highly conserved sequences in genes.

• Define “conserved sequence” of DNA.
• List common examples of the products coded for by conserved sequences of DNA.
• State two hypotheses that account for conserved sequences between species.