Genetic Code

GENETIC CODE

 The genetic code is a remarkable biological system that dictates the translation of nucleic acid sequences into the language of proteins, which are composed of amino acids. Understanding the genetic code was a monumental scientific achievement involving the collaboration of scientists from various disciplines.

 Historical Background:

  • During the early days of molecular biology, it became evident that the genetic material (nucleic acids) somehow controlled the sequence of amino acids in proteins, but the mechanism was unclear.
  • George Gamow, a physicist, proposed that the genetic code should consist of a combination of three nucleotides (triplet code) to account for coding all 20 amino acids.
  • Proving that the code was indeed a triplet code was a significant challenge.

 Key Scientists Involved:

  • Har Gobind Khorana: Developed chemical methods to synthesize RNA molecules with defined base combinations, contributing to the study of the genetic code.
  • Marshall Nirenberg: Developed a cell-free system for protein synthesis that allowed the deciphering of the genetic code.
  • Severo Ochoa: His enzyme, polynucleotide phosphorylase, aided in synthesizing RNA with defined sequences in a template-independent manner.

 Deciphering the Genetic Code:

  • Har Gobind Khorana's methods allowed the synthesis of RNA molecules with specific base combinations.
  •  Marshall Nirenberg's cell-free system for protein synthesis helped in associating codons (triplets of nucleotides) with specific amino acids.
  • This eventually led to the creation of a genetic code checkerboard.

 

 

Key Features of the Genetic Code:

  • Triplet Codons: Each codon consists of three nucleotides. There are 64 possible codons (4 bases raised to the power of 3), which is more than enough to code for the 20 standard amino acids. 
  • Degeneracy: The genetic code is degenerate, meaning that some amino acids are specified by more than one codon. For example, both UUU and UUC code for the amino acid Phenylalanine (phe). This redundancy in the code provides a degree of error tolerance during translation. 
  • Contiguous Reading: Codons are read in a contiguous (continuous) manner along the mRNA molecule. There are no gaps or interruptions in the reading frame.
  •  Universal: The genetic code is nearly universal across all living organisms. For instance, UUU will code for Phenylalanine (phe) in bacteria, plants, animals, and humans. However, there are some exceptions in mitochondrial codons and certain protozoans.
  •  Start and Stop Codons: AUG serves a dual function. It codes for Methionine (met) and acts as the initiator codon, marking the beginning of protein synthesis. UAA, UAG, and UGA are stop codons, signaling the end of translation.

 Mutation and Genetic Code

  • The impact of mutations on genes and DNA is best understood through mutation studies. In this context, the effects of point mutations, particularly insertions and deletions, play a crucial role in altering gene function.
  • Mutations are like spelling mistakes in the genetic code, DNA. These mistakes can happen when DNA is copied.
  • Point Mutation: Imagine a word with three letters, like "CAT." If you change one letter, it becomes something else, like "RAT." That's a point mutation—changing just one letter (base) in the DNA.

Example -

Original DNA: ATG CAT TCA GGA

Mutated DNA (changing one letter): ATG CAT ACA GGA

In this point mutation, the letter 'T' changed to 'A' in the DNA sequence. It can lead to a change in a single amino acid in the protein.

  • Insertion Mutation: Think of a sentence with three-word groups. If you insert an extra word into one group, it messes up the whole sentence. In DNA, adding an extra letter (base) shifts everything, which is called an insertion mutation.

Example- Original DNA: ATG CAT TCA GGA

Mutated DNA (inserting 'C'): ATG CAT CTC AGG A

Here, the letter 'C' was inserted into the sequence, shifting everything afterward. This can cause a frameshift mutation.

  •  Deletion Mutation: Now, if you remove a word from our sentence, it changes everything too. In DNA, deleting a letter (base) also shifts everything, leading to a deletion mutation.

Example- Original DNA: ATG CAT TCA GGA

Mutated DNA (deleting 'T'): AGC ATT CAG GA

In this case, the letter 'T' was removed, also causing a frameshift mutation.

 

Frameshift mutation

 Frame shift mutations are a type of genetic mutation that occurs when nucleotides (the building blocks of DNA) are inserted or deleted from a DNA sequence, causing a shift in the "reading frame" of the genetic code. This shift can lead to significant changes in the resulting protein's amino acid sequence and function.

 Examples:

 Original DNA Sequence:

ATG CAG TCA GGA

 1. Insertion Frame Shift Mutation (Adding a Base 'C'):

 ATG CAG TCA GGA

 ATG CAG CTC AGG A

 In this example, the insertion of the base 'C' caused a frame shift mutation.

This results in a completely different amino acid sequence in the protein and can lead to a non-functional or malfunctioning protein.

 2. Deletion Frame Shift Mutation (Removing 'T'):

 ATG CAG TCA GGA

 AGC AGT CAG GA

 In this example, the deletion of the base 'T' caused a frame shift mutation. The original sequence had a reading frame based on groups of three nucleotides (codons), but after the deletion, the reading frame shifted. As a result, the amino acids encoded by the altered codons will be different, potentially leading to a non-functional protein.

 Impact of Frame Shift Mutations:

  • Frame shift mutations can have significant consequences. They often result in the production of a truncated (shortened) protein or a completely non-functional one. These mutations are commonly associated with genetic disorders and diseases. For example, diseases like cystic fibrosis and Tay-Sachs disease can be caused by frameshift mutations in specific genes.
  •  Understanding frame shift mutations is crucial in genetics and biology because they highlight how small changes in the DNA sequence can lead to significant alterations in protein structure and function, ultimately affecting an organism's health and development.

 

tRNA the Adapter molecule

 tRNA, also known as transfer RNA, plays a crucial role as an adapter molecule in the process of protein synthesis. It was postulated by Francis Crick to read the genetic code and link it to specific amino acids. Each tRNA molecule has a unique anticodon loop that contains bases complementary to the codons in mRNA, allowing it to recognize and bind to the corresponding codon. Additionally, tRNA possesses an amino acid acceptor end to which it attaches specific amino acids.

 Structure of tRNA:

 1. Cloverleaf Structure: Transfer RNA (tRNA) molecules have a characteristic cloverleaf-like secondary structure. This structure consists of several key features:

  •  An anticodon loop: This loop contains three nucleotides that are complementary to a specific mRNA codon, allowing tRNA to recognize and bind to the mRNA.
  • An amino acid acceptor stem: This stem holds the corresponding amino acid attached to the tRNA.
  •  D-arm (dihydrouridine arm): A secondary structure element essential for tRNA stability.
  • T-arm (thymidine arm): Another structural feature that contributes to tRNA stability.
  •  Variable loop: A loop region with varying sequences, which can differ among different tRNA molecules.

 

2. Inverted L-shape: In its three-dimensional structure, tRNA appears as an inverted L-shape due to the folding of its cloverleaf secondary structure.

 

 

Function of tRNA:

  • Adapter Molecule: tRNA acts as an adapter molecule during protein synthesis, connecting the genetic code carried by mRNA to the specific amino acids required for protein assembly. 
  • Amino Acid Binding: Each tRNA molecule is specific to a particular amino acid. The amino acid is attached to the tRNA at the 3' end, forming an aminoacyl-tRNA. 
  •  Anticodon Recognition: The anticodon loop of tRNA contains three nucleotides that are complementary to a specific mRNA codon. This enables tRNA to recognize and bind to the mRNA codon through base-pairing interactions. 
  •  Initiation: During translation initiation, a specialized initiator tRNA carrying methionine (Met) binds to the start codon AUG on the mRNA. This initiator tRNA ensures the correct placement of the first amino acid in the growing polypeptide chain. 
  • Elongation: In the elongation phase of translation, tRNAs with attached amino acids enter the ribosome and match their anticodons with the complementary codons on the mRNA. This facilitates the addition of amino acids to the growing polypeptide chain in the correct sequence. 
  • Termination: When a stop codon (UAA, UAG, or UGA) is encountered on the mRNA, release factors bind to it, leading to the termination of protein synthesis. No tRNA molecules correspond to stop codons.