Genetic Code & Central Dogma

The Genetic Code

• The genetic code is contained in DNA, transcribed to mRNA, and translated into proteins.
• The code is degenerate, meaning that multiple codons can code for the same amino acid.

Central Dogma

• The central dogma states that DNA is transcribed into mRNA, which is then translated into proteins.
• The process does not involve a code, but rather the synthesis of mRNA through base pairing.

Cracking the Genetic Code

• The genetic code was cracked through a series of experiments, including:
  • Synthesizing poly(U) and poly(A) to test codon combinations.
  • Using ribosomes to translate synthesized RNA.
  • Determining the sequence of nucleotides in tRNA.
• The code was found to be degenerate, with multiple codons coding for the same amino acid.

Codon Assignment

• Codons were assigned to amino acids through experimentation.
• The first position of the codon is most important in determining the amino acid.
• The second position is also important, while the third position is less important.
• Some amino acids have multiple codons, while others have only one.

tRNA and the Wobble Hypothesis

• tRNA recognizes codons through complementary base pairing.
• The Wobble Hypothesis states that the third base of the codon can undergo non-canonical pairing, allowing a single tRNA to recognize multiple codons.
• This allows for degeneracy in the code and reduces the number of tRNAs needed.

Codon Bias and Optimal Codons

• Codon bias refers to the preference for certain codons over others in an organism.
• Optimal codons are those that are used most frequently and are recognized by abundant tRNAs.
• The use of optimal codons can affect the speed of translation and the efficiency of protein synthesis.
• Non-optimal codons can cause ribosome stalling and affect protein synthesis.

Summary

• The genetic code is degenerate, with multiple codons coding for the same amino acid.
• Codon assignment was determined through experimentation.
• tRNA recognizes codons through complementary base pairing, and the Wobble Hypothesis explains degeneracy in the code.
• Codon bias and the use of optimal codons can affect protein synthesis.### Non-Optimal Codons and Protein Synthesis
• Non-optimal codons produce less protein and have reduced stability, leading to ribosome stalling and degradation.
• Rapid translation is not always beneficial, as it can lead to misfolding.

Regulation of Gene Expression by tRNAs

• In multicellular organisms, tRNA population varies between cells undergoing differentiation or proliferation.
• Cells undergoing differentiation have a tRNA population that translates specific mRNAs, while proliferating cells have a tRNA population enriched for specific codons.
• In tumors, cell populations switch from a differentiated to a proliferative state, altering tRNA expression and promoting metastasis.

Suppressor tRNAs

• Mutations in the anticodon of a tRNA can cause it to read a different codon, leading to mistranslation and mutations.
• Such mutations can be difficult to recognize.

Mitochondrial Genetic Code

• Mitochondria have a reduced genetic code with fewer tRNAs due to genomic pressure.
• The code has evolved independently, with changes such as stop codons becoming tryptophan codons.

Universality of the Genetic Code

• The genetic code is universal, but there are exceptions in nuclear genomes.
• Some organisms have modified codons, such as Mycoplasma capricolium, where UGA codes for tryptophan.

New Amino Acids

• Selenocysteine (Sec) is the 21st amino acid, found in all organisms, and has antioxidant properties.
• Pyrrolysine (Pyl) is the 22nd amino acid, found only in eubacteria and archaea, and is encoded by the UAG codon.

Origin and Evolution of the Genetic Code

• The "frozen accident" hypothesis proposes that the genetic code arose randomly and was frozen in place.
• The stereochemical hypothesis suggests that the code arose from direct interactions between RNA and amino acids.
• The co-evolution hypothesis proposes that the code co-evolved with the expansion of the amino acid repertoire.