Indian
behind Biological Code
When we talk of life
there are 3 essential macromolecules that lead whole of life processes. These
molecules constitute the central dogma. (DNA to RNA, RNA to Protein)
A DNA transfers its
information to form RNA, RNA consequently end in amino acids. Amino acids
linked each other by peptide bond. The peptide bonds with the help of united
weaker forces aggregate themselves in a definite orientation to form a
functional protein.
It is this protein
structure that is pivotal in every metabolic pathway of life as enzyme, It is
responsible for protection (immunity), reproduction and behind every life
processes there will be protein. Hence it is said “Proteins are the building
blocks of Life.
There are many scientists
who contributed in solving the mystery of protein. Linus Pauling successfully
predicted the regular protein structure based on Hydrogen Bonding. Walter
Kuzman contributed an understanding of protein and structure mediated by
hydrophobic interaction. Sanger sequenced “Insulin”- the first protein to be sequenced
(every amino acid and its position is determined) and many more of them
contributed to solve the central dogma including Watson and Crick.
Despite of ample of research
on structure of DNA, RNA, and Protein the central dogma was still a misery. It
was a question to scientific world, How 4 bases in DNA (Adenine, Guanine,
Cytosine, Thymine) turn into such diverse form proteins. It was an Indian Har Gobind Khorana along with Marshall .W.
Nirenberg and Robert Holly quest the code of life” The genetic code”. It says
that combination of 3 bases (triplet Codon) in DNA read as mRNA and these 3
letter code in mRNA determine the amino acid to be produced.
A codon is defined by the initial nucleotide from which
translation starts. For example, the string GGGAAACCC, if read from the first
position, contains the codons GGG, AAA, and CCC; and, if read from the second
position, it contains the codons GGA and AAC; if read starting from the third
position, GAA and ACC. Every sequence can, thus, be read in three reading frames, each
of which will produce a different amino acid sequence (in the given example,
Gly-Lys-Pro, Gly-Asn, or Glu-Thr, respectively). With double-stranded DNA,
there are six possible reading frames, three
in the forward orientation on one strand and three reverse on the opposite
strand. The actual frame in which a protein
sequence is translated is defined by a start codon, usually the first AUG codon in the mRNA
sequence.
The genetic code has redundancy but no ambiguity. For
example, although codons GAA and GAG both specify glutamic acid (redundancy),
neither of them specifies any other amino acid (no ambiguity). The codons
encoding one amino acid may differ in any of their three positions. For example
the amino acid leucine is specified by YUR or CUN (UUA, UUG, CUU, CUC, CUA, or CUG) codons
(difference in the first or third position indicated using IUPAC
notation),
while the amino acid serine is specified by UCN or AGY(UCA, UCG, UCC, UCU, AGU, or AGC) codons
(difference in the first, second, or third position).
Khorana who made Indians pride was the first
receiver of Nobel Prize in physiology and medicine in the year 1968 who is
Indian origin.
Khorana was born in Raipur Village west Punjab,
British India (today Pakistan) to Hindu parents. He was home schooled by his father until high school. He
earned his B.Sc from Punjab
University, Lahore, in 1943, and his M.Sc from Punjab
University, Lahore in 1945. In 1945, he began studying at the University
of Liverpool. After
earning a Ph.D in 1948, he continued his postdoctoral studies in Zürich (1948–1949). Subsequently, he spent two
years at Cambridge
University. In
1952 he went to the University
of British Columbia, Vancouver and in 1960 moved to the University
of Wisconsin–Madison. In 1970 Khorana
became the Alfred Sloan Professor of Biology and Chemistry at the Massachusetts
Institute of Technology where he
worked until retiring in 2007.
His work consists of Ribonucleic acid (RNA) with three
repeating units (UCUCUCU → UCU CUC UCU) produced two alternating amino acids. This, combined with the Nirenberg and Leder
experiment, showed that UCU codes for Serine and CUC codes for Leucine. RNAs with three repeating units (UACUACUA → UAC
UAC UAC, or ACU ACU ACU, or CUA CUA CUA) produced three different strings of
amino acids. RNAs with four repeating units including UAG, UAA, or UGA,
produced only dipeptides and tripeptides thus
revealing that UAG, UAA and UGA are stop codons.
With this, Khorana and his team had established
that the mother of all codes,
the biological language common to all living organisms, is spelled out in
three-letter words: each set of three nucleotides codes
for a specific amino acid. Their Nobel lecture
was delivered on December 12, 1968. Khorana was the
first scientist to synthesize oligonucleotides.
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