Lecture 16: Genetic changes & protein function Flashcards
Outline the 3 step process of translation:
- Initiation: The ribosome, mRNA, and the first tRNA come together to form the translation initiation complex.
- The first tRNA always codes for a methionine (AUG codon/UAC anti-codon). - Elongation: The ribosome moves along the mRNA, adding amino acids to the growing peptide chain.
- Termination: A “stop codon” indicates the peptide chain has all the necessary amino acids and causes the translation complex to break apart. Releases the newly formed peptide chain (ready for protein folding and post-translational modification).
What is the purpose of translation and where does it occur?
The purpose is to make a polypeptide chain using the message encoded by mRNA.
Translation occurs in the cytoplasm and is carried out by ribosomes.
What are ribosomes?
Ribosomes are structures made of protein and rRNA. They work like enzymes to catalyse protein synthesis (peptide bond reaction).
What is the role of tRNA in the translation process?
tRNA reads the codons in mRNA. tRNA has an anti-codon which is complementary to the mRNA codon. The tRNA has an amino acid attached to it which matches its anti-codon.
What is meant by “codon redundancy”?
There are 64 possible codons and 20 amino acids. This means that multiple codons can code for the same amino acid (except Met and Trp).
What is genetic variation and how is it important to a species?
Genetic variation refer to the differences between the DNA sequences of members of the same species. It is important as it helps determine who is who, helps a species survive, and helps organisms adapt to their environment.
What is a genetic variant?
A specific difference between individuals.
What are 3 examples of non-coding variants?
- Regulatory variants
- Intron variants
- Intergenic variants
What is the consequence of a variant in a regulatory region (non-coding) and within the exon of a gene (coding)?
Non-coding: it may change the amount of protein produced
Coding: it may change the amino acid sequence and function of a protein.
Variants can have no, minor, or major consequences.
What are the 2 different types of genetic variants and what are the consequences of them?
- SNP: single nucleotide polymorphism, a single base change in the DNA sequence e.g. an A nucleotide changed to a G nucleotide.
- synonymous; altered codon specifies same amino acid
- missense; altered codon specifies different amino acid
- nonsense; altered codon specifies stop - InDel: insertion-deletion, the addition or removal of one or more bases e.g. AAT sequence changed to AACT sequence – C is added.
- inframe deletion/insertion; loss/gain of one amino acid. All codons after variant read correctly
- frameshift deletion/insertion; causes all codons after variant to be read incorrectly
What do the consequences of a missense genetic variant depend on?
- Where in the protein the amino acid change occurs, e.g: In an enzyme active site or receptor ligand binding site.
- How chemically similar/different the two amino acids are, e.g: Polar charged → non-polar
- Whether the amino acid breaks an essential structure, e.g: Proline (helix breaker) added to an alpha-helix or Cysteine removed from one side of a disulfide bond.
What type of protein can be affected by a genetic variant?
Every type of protein can be affected by any type of genetic variant. Variants causing complete loss of function to a protein essential for life will be lethal, e.g. complete loss of DNA polymerase function – no ability to replicate cells.
What are 3 ‘real life’ examples of missense variants?
- Benign missense variant: (V55I) valine to isoleucine; no known consequences
- Pathogenic Missense Variant: (E6V)
Glutamic Acid to Valine; Sickle Cell Anaemia - Pathogenic Missense Variant:
(H64Y) Histidine to Tyrosine
Methaemoglobinaemia: Fe3+ haem – unable to bind oxygen.
