Indian behind Biological Code

Indian behind Biological Code

Man has landed on moon, constructed machine efficient than himself, created robots that would behave like him, created techniques to form life artificially, despite, the life is still a mystery. There are millions of things unaware about life. Either it is the biochemical processes and cell signaling or the introns in eukaryotes. Behavior of cells or else the formation of cells, there are a no of things that still remain mystery.

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.