what three technical advances in the 1960s allowed researchers to crack the genetic code
Life (Basel). 2016 Sep; 6(iii): 36.
The Genetic Code: Francis Crick's Legacy and Beyond
Koji Tamura
1Section of Biological science and Technology, Tokyo University of Scientific discipline, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan; pj.ca.sut.sr@ijok; Tel.: +81-3-5876-1472
2Research Plant for Science and Technology, Tokyo University of Scientific discipline, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
David Deamer, Academic Editor
Received 2016 Aug 22; Accepted 2016 Aug 23.
Francis Crick (Figure 1) was born on 8 June 1916, in Northampton, England, and passed away on 28 July 2004, in La Jolla, California, USA. This twelvemonth, 2016, marks the 100th anniversary of his nativity. A drastic change in the life sciences was brought about by the discovery of the double helical structure of Deoxyribonucleic acid by James Watson and Francis Crick in 1953 [1], eventually leading to the deciphering of the genetic code [2]. The elucidation of the genetic code was ane of the greatest discoveries of the 20th century. The genetic code is an algorithm that connects 64 RNA triplets to twenty amino acids, and functions as the Rosetta stone of molecular biology.
Sir Francis Crick, La Jolla 1982, Photo by Norman Seeff. Credit: Norman Seeff Productions.
At the historic period of 60, Crick moved to La Jolla from Cambridge, England, and shifted his focus to the encephalon and human consciousness. He tackled this field of study for the final 28 years of his life. His life-long interest was the distinction between the living and the non-living, which motivated his research career. Crick was arguably 1 of the 20th century's most influential scientists, and he devoted himself to science until his death.
Francis Crick continued to practise his intellectual abilities throughout his life. His research fashion was characterized by collaborations with outstanding partners, James Watson in discovering the structure of Dna, Sydney Brenner in swell the genetic code, Leslie Orgel in probing the origins of life, and Christof Koch in agreement human consciousness. Francis Crick was never modest in his choice of scientific problems [3] and was similar "the usher of the scientific orchestra" [iv]. He always discussed his ideas, which helped in the progress he made in science. Interestingly, his son, Michael, and then 12 years old, was the outset person to read the earliest written description of the genetic code. Crick wrote the following in a letter to Michael,
"…Now nosotros believe that the D.N.A. is a code. That is, the guild of the bases (the letters) makes one cistron unlike from another gene (simply equally one page of print is unlike from another). You tin now see how Nature makes copies of the genes. Because if the two chains unwind into two separate chains, and if each chain then makes another chain come up together on it, then because A always goes with T, and One thousand with C, nosotros shall go two copies where…"
Letter from Francis Crick to his son, Michael, explaining his and Watson's discovery of the structure of DNA. The letter is the earliest written clarification of the genetic mechanism on 19 March 1953. Credit: Wellcome Library, London.
This is the central principle of biology. The large questions that arose subsequently the discovery of the structure of DNA were "how is the code used?" and "what is it a code for?" Francis Crick turned his attention to find answers to these questions for the next 13 years. George Gamow, who is famous for the Big Blindside theory, founded the 20-member "RNA Tie Order" with Watson, to hash out the transmission of information by DNA. RNA-illustrated neckties were provided to all members, and a golden tiepin with the abridgement for one of the 20 amino acids was given to each member. Crick was "TYR" (tyrosine). Crick'due south famous "adaptor hypothesis" was prepared for apportionment in the RNA Tie Club [5], only when Paul Zamecnik and collaborators discovered transfer RNA (tRNA) [6], Crick did non believe that it was indeed the adaptor, because of its unexpectedly large size. Crick insisted that at that place would be 20 different adaptors for the amino acids, and that they would bring the amino acids to bring together the sequence of a nascent protein. A manuscript entitled "Ideas on protein synthesis (October, 1956)" remains extant (Figure 3). Crick spoke about "The Central Dogma" at a Society for Experimental Biology symposium on "The Biological Replication of Macromolecules", held at the Academy College London in September, 1957. The Central Dogma holds truthful fifty-fifty today, and is another example of Crick's genius.
The earliest written description of "The Cardinal Dogma" in a manuscript entitled "Ideas on protein synthesis (Oct 1956)". Credit: Wellcome Library, London.
In 1961, Francis Crick, Sydney Brenner, Leslie Barnett, and Richard Watts-Tobin first demonstrated the 3 bases of DNA code for one amino acid [7]. That was the moment that scientists cracked the lawmaking of life. Even so, ironically, the first decoding of the "give-and-take" of the genetic code was reported in the same twelvemonth past a non-member of the RNA Tie Order, Marshall Nirenberg, who spoke at the International Biochemical Congress in Moscow. Matthew Meselson heard Nirenberg's 15-minute talk in a small room and told Crick about it. Crick arranged for Nirenberg to give the talk again at the end of the meeting. Starting with Nirenberg and Heinrich Matthaei's piece of work [8], followed by that of Nirenberg and Philip Leder [9], the decoding was completed by Har Gobind Khorana [10]. Finally, Brenner, Barnett, Eugene Katz, and Crick placed the final slice of the jigsaw puzzle of life by proving that UGA was a third stop codon [xi].
Thus, the genetic code was cracked, and it is the greatest legacy left backside by Francis Crick, along with the discovery of the double helical nature of DNA. As hallmarks of the foundation of molecular biology, they volition go along to shine forever. However, the origin and evolution of the genetic lawmaking remain a mystery, despite numerous theories and attempts to understand them. In the mid-1960s, Carl Woese proposed the "stereochemical hypothesis", which suggested that the genetic lawmaking is derived from a blazon of codon–amino acrid pairing interaction [12]. On the other manus, Crick proposed the "frozen blow hypothesis" and conjectured that the genetic code evolved from the last universal common ancestor and was frozen in one case established. Even so, he explicitly left room for stereochemical interactions between amino acids and their coding nucleotides, stating that "It is therefore essential to pursue the stereochemical theory…vague models of such interactions are of little use. What is wanted is direct experimental proof that these interactions take place…and some idea of their specificity" [13].
What is the real origin of the genetic code? tRNAs and aminoacyl-tRNA synthetases play central roles in translating the genetic code in the present biological system [xiv], just what could have been the archaic forms of these molecules? Although Crick idea that tRNA seemed to be nature's attempt to make RNA do the task of a protein [2], the primordial genetic code prior to the establishment of the universal genetic code might have resided in a archaic form of tRNA. Such an example of "operational RNA code" [15] may be seen as a remnant in the acceptor stem of tRNA, which still functions equally a critical recognition site by an aminoacyl-tRNA synthetase [16,17,18]. In addition, why are xx amino acids involved in the genetic code? Bigotry of an amino acid with the high fidelity attained by modern aminoacyl-tRNA synthetases (mistake rate as low as 1/40,000 [19]) would be impossible using a simple thermodynamic process lone, because the hydrophobic bounden energy of a methylene group is, at the almost, ~i kcal/mol. Therefore, several sets of amino acids with similar side bondage might take been coded non-selectively in the primitive stage [20]. Furthermore, the genetic lawmaking is the human relationship between left-handed amino acids and right-handed nucleic acids. As non-enzymatic tRNA aminoacylation has been shown to occur chiral-selectively [21], the establishment of the genetic lawmaking might be closely associated with the evolutionary transition from the putative "RNA world" to the "RNA/protein earth" in terms of homochirality [22]. All these are disquisitional problems that should be investigated in the futurity.
The life force of Francis Crick was once described as similar to the "incandescence of an intellectual nuclear reactor" [23]. His passion for science is an inspiration for future scientific explorers. The Guest Editor of this Special Issue dedicates all articles included herein to the memory of Francis Crick.
Acknowledgments
The author cheers Kindra Crick for her valuable comments and suggestions.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041012/
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