Genetic Changes and Protein Function Flashcards
Brief overview of Translation
- Occurs in the cytoplasm
- Carried out by ribsomses
- Ribosomes are complex structures made of protein and rRNA
- Ribosomes work like enzymes to catalyse protein synthesis (peptide bond reaction)
- There are four unique nucleobases in DNA or RNA (DNA: t, RNA u)
- There are 20 unique AAs
- the code of DNA has to be read in sets of threes known as codons to make an AA
- The codon system is common across all life and is known as the ‘universal genetic code’
Describe the role of tRNA in translation
Codons in mRNA are ‘read’ by another RNA molecule called tRNA
- has an anti-codoc - the complementary sequence to the mRNA codon
- Has an amino acid attached
- every codon/anti-codon sequence has a particular amino acid that it pairs with
- the tRNA attaches to the amino acid, and only the amino acid that matches tRNA molecules’ anti-codon will be able to match
- ensures the same mRNA sequence is always translated the same way (always makes the same protein)
Describe the three stages of translation
Initiation: the ribosome, mRNA and the first rRNA come together to form the translation initiation complex
- the first tRNA always codes for 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 that 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)
Describe codons and redundancy
There are 64 possible codons
- four bases, 3 per codon 4 to the 3 = 64
There are 20 AA’s (plus ‘stop’)
Each amino acid can be coded for by multiple codons
- except methionine (Met) and tryptophan (Trp)
Known as codon redundancy
- allows for some flexibility in gene sequence, without changing the protein
Describe genetic variation
- Genetic variation refers to the differences between the DNA sequences of members of the same species
- humans are 0.1% different to each other at the DNA sequence level
- whole diploid human genome is made up of 6 million base pairs
- Genetic variation is important in any species (to determine who is who, helps species survive, helps organisms adapt to their environment)
- genetic variant refers to a specific difference between individuals
- in the sae location in the DNA, different forms of a variant are called alleles
Describe the types of genetic variant
Genetic variants can be classified based on:
- number of DNA bases involved
- style of DNA sequence involved (repetition of DNA sequence vs. one-off differences)
- location of the change
In BIOC192 we will focus on single-base variants or small insertion/deletion variants found inside genes
- SNP: single nucleotide polymorphism, a single base change in the DNA sequence
- InDel: insertion-deletion, the addition or removal of one or more bases
Describe the consequences of genetic variants
- Most variants are neutral (have no consequences)
- Variants in a regulatory region (non-coding variants) may change the expression of a gene (this changes the amount of protein that is produced)
- Variants within the exon of a gene (coding variants) may change the amino acid sequence, and potentially the function, of a protein
- Coding variants can have no, minor or major consequences
Describe the specific types of consequences of genetic variants (name and what it does)
SNPs:
- Synonymous: altered codon specifies the same amino acid
- Missense: altered codon specifies one different amino acid
- Non-sense: altered codon specifies a translation stop signal (protein is too short)
InDel: usually has serious consequences for the protein
- Inframe insertion and Inframe deletion: Gain/loss of one amino acid. all codons after variant are read correctly
- Frame shift insertion or frame shift deletion: Frameshift causes all codons after the variant to be read incorrectly
Describe the consequences of a missense genetic variant to the proteins function
The consequences depend on:
- where in the protein the amino acid change occurs (in an enzyme active site or receptor ligand binding site)
- how chemically similar/different the two amino acids are (ie. polar changed to polar or if polar charged changed to non-polar would be much worse)
- whether the amino acid breaks an essential structure (proline is a helix breaker so if that’s added to alpha helix that’s bad or if cysteine is removed from one side of the disulphide bond)
- the original function of the protein
Describe the types of proteins affected from genetic variants
Genetic variants are found in every gene
- every type of protein can be affected by a genetic variant
Every type of protein can have any type of genetic variant
- leads to the wide variety of differences between organisms
- Variations causing complete loss of function to a protein essential for life will be lethal
(could be storage, catalysis, defence, transport, signalling, structure, growth/maintenance)
Briefly explain what the sonsequences of a missense variant to an organism depend on
The consequences of a mis sense variant to an organism depend on:
- how important the protein’s job is
- whether another protein can compensate for the changed proteins function
- whether the protein lost its function or gained a new function
describe the haemoglobin variants
Haemoglobin (beta subunit): most recorded variants are synonymous or missense changes
- HBB V55I - valine changes to isoleucine at AA 55 (no known consequences)
- HBB E6V - glutamate changes to valine at AA 6 (sickle cell anemia - ‘sticky’ Hb proteins clog blood vessels)
- HBB H64Y - histamine changes to tyrosine at AA 64 (methaemoglobinaemia - Fe3+, unable to bind oxygen)
