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Molecular Basis of Inheritance

Translation

We have learned that the process of transcription converts the information in DNA to RNA. How is the information in the RNA then used to synthesize proteins? Transcription is followed by a process called translation which involves decoding the instructions in the RNA to make proteins. How exactly does this work? Let’s find out below.

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Genetic Code

In replication and transcription, a nucleic acid is copied to make another nucleic acid. Both these processes work on the basis of complementarity. Translation, however, converts genetic information from a polymer of nucleotides to a polymer of amino acids. This is not based on complementarity. Then, how does this process take place?

You may have seen barcodes on items in a grocery store. These barcodes are used to identify the item. Scanning the barcode helps the store to track that item. In the same way, there also exists a genetic code. It is a set of rules on the mRNA that tells the cell which amino acid should be added to the polymer.

The process of deciphering this genetic code was extremely challenging and involved multiple scientists from different areas. Let’s learn who they were and how they contributed.

  • George Gamow – a physicist who proposed that if 4 bases (adenine, guanine, cytosine, uracil) have to code for 20 amino acids, the genetic code must be a combination of three bases (a triplet). According to this, a permutation combination of 43 (4 x 4 x 4) will give 64 codons, which is more than the number of amino acids.
  • Har Gobind Khorana – a biochemist who developed the chemical method to synthesize RNA molecules with defined combination of bases. These molecules were instrumental in deciphering the genetic code.
  • Marshall Nirenberg – a biochemist and geneticist who developed a cell-free system for protein synthesis that helped to finally decipher the genetic code.
  • Severo Ochoa – a biochemist who discovered an enzyme that allowed him to synthesize RNA with defined sequences, without the use of a DNA template.

The work of all these scientists finally gave a checkerboard for the genetic code as shown below:

Translation

The codons for different amino acids [Source: Wikimedia Commons]

Salient Features of the Genetic Code

  • Each codon is a triplet of bases. There are 64 codons in total, of which 61 code for amino acids while 3 act as stop codons during translation.
  • One codon codes for only one amino acid. Therefore, it is specific and unambiguous.
  • Some amino acids are coded for by more than one codon. For example, GUU, GUC, GUA, and GUG – all code for valine (Val). Therefore, the code is degenerate.
  • The codons on the mRNA are read in a continuous manner, without any punctuations.
  • The genetic code is universal i.e. from bacteria to humans, the code UUU refers to phenylalanine (Phe). However, there are some exceptions to this rule, such as mitochondrial codons.
  • The codon AUG has dual functions. It codes for the amino acid methionine (Met) and is also the start/initiator codon.

The Genetic Code And Mutations

You may have already learned about mutations that involve large deletions or rearrangement of segments of DNA. These result in loss or gain of a gene and therefore, a function. What about mutations or changes in a single base pair of a codon? These are called point mutations. A classic example is a point mutation in a gene for beta globin chain.

A change in a single base pair in this gene changes the amino acid glutamine to valine. This results in a disease called sickle cell anaemia. There are other types of mutations too. Let’s use the following statement with three-letter words like the genetic code, as an example:

TOM HAS BIG TOE

  • Now, insert one letter in the middle – TOM HAS OBI GTO E
  • Now, insert two letters – TOM HAS ONB IGT OE

In both the above cases, the frame of reading is shifted changing the meaning of the sentence. If similar insertions of one or two bases happen in the genetic code, the frame will shift and change the sequence of amino acids added. This is called a frameshift insertion.

  • Now, delete the letter from the above sentence – TOM HAS IGT OE
  • Now, delete from the above sentence – TOM HAS GTO E

Again, the frame has shifted changing the meaning of the sentence. But, this time letters were deleted, so this is a frameshift deletion. Inserting or deleting three letters (or multiples of three) adds or deletes one codon and therefore, one amino acid. This does not affect the reading frame. Let’s use the above sentence as an example.

  • Inserting three letters – TOM HAS ONE BIG TOE
  • Deleting three letters (B, I, G) – TOM HAS TOE

The Adaptor Molecule – tRNA

Amino acids have no special ability to read the codons. Then how are the codons read? Francis Crick proposed that there is an ‘adaptor molecule’ that reads the codons and also binds to specific amino acids. This adaptor molecule was found to be tRNA or transfer RNA. The tRNA has the following parts:

  • Anticodon loop – that has bases that are complementary to the codon on the mRNA.
  • Amino acid acceptor end – It uses this end to bind to amino acids.

There are specific tRNAs for each amino acid. A special tRNA called initiator tRNA initiates the process of translation. There are no tRNAs for stop codons.

Translation

Cloverleaf structure of tRNA [Source: Wikimedia Commons]

Translation

It is the process of polymerization of amino acids to give rise to a polypeptide. The amino acids in the polypeptide are joined by peptide bonds. The sequence of amino acids is governed by the sequence of bases on the mRNA. In mRNA, a translational unit is a region that begins with the start codon (AUG), ends with the stop codon and codes for a polypeptide.

A mRNA also has some additional, untranslated regions or UTRs. They exist before the start codon at the 5′ end and after the stop codon at the 3′ end and are essential for efficient translation. Like transcription, translation has the following three steps.

Initiation

Translation occurs in the ribosome. In the inactive state, the ribosome consists of a large and small subunit. Translation begins when the small subunit encounters a mRNA. The ribosome binds to the start codon (AUG) on the mRNA to initiate translation. The initiator tRNA brings the first amino acid encoded by AUG i.e. methionine.

This phase also involves activation of amino acids in the presence of ATP and linking to their specific tRNA. This is called charging of tRNA or aminoacylation of tRNA. When two charged tRNAs are close enough, it favours formation of a peptide bond between them. The large subunit of the ribosome has two sites for subsequent amino acids to bind and to be close enough to form peptide bonds. The ribosome also acts as a catalyst for peptide bond formation.

Elongation

Elongation involves the stepwise addition of amino acids to the growing polypeptide chain. In this phase, the new amino acid-tRNA complex binds to the complementary codon on the mRNA via the anticodon on the tRNA. Next, the bond between the tRNA and amino acid breaks and a new peptide bond forms between the new and previous amino acids on the growing chain.

After adding each new amino acid to the polypeptide, the ribosome moves down to a new codon on the mRNA. This releases the previous tRNA, which is now free to bring another amino acid. These steps repeat till the ribosome reaches the stop codon on the mRNA.

Termination

Elongation continues till the ribosome reaches the stop codons (UAA or UAG or UGA). At this point, a release factor binds to the stop codon and terminates translation by releasing the polypeptide and mRNA from the ribosome.

Translation

Translation [Source: Wikimedia Commons]

Solved Example For You

Q1: Use the genetic code checkerboard to list the amino acid sequence resulting from the following mRNA sequence: 5′-A U A G C A G G A C U U-3′.

Sol: The answer is 5′- isoleucine-alanine-glycine-leucine -3′. If you use the checkerboard, you can see that AUA codes for isoleucine, GCA codes for alanine, GGA codes for glycine and CUU codes for leucine.

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