The Genetic Code: Deciphering & How it Works

Classes 10 & 11

Code

a system of symbols that equates information in one language with information in another

Codon

• each nucleotide triplet

• specifies one amino acid

• is only relevant during translation

• RNA dialect (U instead of T)

• non-overlapping

Missense mutation

change a codon for one amino acid into a codon that specifies a different amino acid

Intragenic suppression

the restoration of gene function by one mutation canceling another in the same gene

Reading frame

the sequential partitioning of nucleotides into groups of three to generate the correct order of amino acids in the resulting polypeptide

Frameshift mutations

• shift in the reading frame for all codons beyond the point of insertion or deletion (downstream)

• usually screws up the function of the polypeptide product

• a deletion can counter-balance an insertion, but only if the portion of polypeptide encoded between the two mutations of opposite sign is not required for protein function

  • ex: portion of polypeptide should NOT be at active site

Degenerate characteristic of genetic code

• multiple nucleotide triplets specify one of the 20 amino acids

• 4 total nucleotides and triplet nucleotides creating a codon = 4³ = 64 different combinations of the three nucleotides

  • 64 combos - 20 amino acids = 44 noncoding triplets

In vitro test/studies

• "cell-free”

• cellular extracts + mRNA = synthesizing polypeptides in a test tube

• experiment to see what nucleotide triplets made what amino acid

• studies that analyze how mutations actually affect the amino acid composition of polypeptides encoded by a gene

Stop codon

• RNAs that have signals that stop the construction of a polypeptide chain

• when they appear in the reading frame, translation stops

• UAA, UAG, UGA

• DO NOT code for anything = nonsense codon

Nonsense mutation

a codon is changed from one that signifies an amino acid to one that does not

Genetic code

a complete dictionary equating the 4-letter language of nucleic acids with the 20-letter language of proteins

Start codon

• nucleotide triplet that specifies the amino acid methionine (Met) wherever it appears in the reading frame

• marks where in an mRNA the code for a particular polypeptide begins

Transcription

process by which the polymerization of ribonucleotides (through complementary base pairing) produces an RNA transcript of a gene

Translation

• the process by which the sequence of nucleotides in an mRNA directs the assembly of the correct sequence of amino acids in the corresponding polypeptide

• very messy with many mistakes, but is tolerable because of degeneracy of genetic code

Ribosomes

• coordinate the movement of tRNAs carrying specific amino acids with the genetic instructions of an mRNA

• recognize features that signal the start of translation

• supply the enzymatic activity that links the amino acids

• move 5’ to 3’ along mRNA, exposing mRNA codons in sequence, ensuring the linear addition of amino acids

• help end polypeptide synthesis by dissociating the mRNA directing polypeptide construction and from the actual peptide

Transfer RNAs

• serve as adapter molecules that mediate the transfer of information from nucleic acid to protein

• short, single-stranded RNA molecules

  • primary structure: a nucleotide sequence

  • secondary structure: short, complementary regions with single strand that pairs with itself

  • tertiary structure: 3D folding

• all cells have at least one type for each of the common 20 amino acids

• each carries one specific amino acid

• 32 species

Aminoacyl-tRNA synthetases

• connect tRNA to the amino acid that corresponds to the anticodon

• the only molecules that read the languages of both nucleic acid and protein

• each one only functions for one amino acid

• establishes the covalent bond between amino acid and the 3’ end of its tRNA

Anticodon

• three nucleotides complementary to an mRNA codon

• anti-parallel

• can only bind to one amino acid’s codon

Wobble

• the flexibility in base pairing between the 3’ nucleotide in the codon and the 5’ nucleotide in the anticodon

• so long as first two nucleotides correspond to a certain amino acid, the third letter (3’ end) “doesn’t matter”

  • explains why multiple codons for a single amino acid usually start with the same two letters

• bases are chemically modified at 5’ end of the anticodon

  • there’s a weak bond between this position and the base that isn’t typically “supposed” to be bound

Post-translational modifications

• enzymatic addition of chemical constituents to specific amino acids modify a polypeptide after translation

  • ex: adding phosphate groups, carbohydrates, fatty acids, other small peptides

• may alter the way protein folds, its ability to interact with other proteins, its activity, or its location in the cell

• can cleave polypeptide

Noncoding genes

• genes transcribed but NOT translated

• ex: genes for rRNAs, tRNAs, snRNAs

Nonsense suppressor tRNAs

• mutations in certain tRNA genes that can suppress the effects of nonsense mutations in other genes

• its anticodon is something that it shouldn’t (mutated), but it still puts the amino acids that it’s meant to put