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Nirenberg and Leder experiment
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==Background== [[Oswald Avery]] discovered that the substance responsible for producing inheritable change in the disease-causing bacteria was neither a protein nor a lipid, rather deoxyribonucleic acid ([[DNA]]). He and his colleagues [[Colin Munro MacLeod|Colin MacLeod]] and [[Maclyn McCarty]] suggested that DNA was responsible for transferring genetic information. Later, [[Erwin Chargaff]] discovered that the makeup of DNA differs from one species to another. These experiments helped pave the way for the discovery of the structure of DNA. In 1953, with the help of [[Maurice Wilkins]] and [[Rosalind Franklin]]βs [[X-ray crystallography]], [[James D. Watson|James Watson]] and [[Francis Crick]] proposed DNA is structured as a [[double helix]].<ref>{{Cite book | title= iGenetics: A Molecular Approach, 3rd edition | author=Russell P. |year=2010| publisher= Pearson/Benjamin Cummings }}</ref> In the 1960s, one main DNA mystery scientists needed to figure out was in [[translation (genetics)|translation]] how many bases would be in each code word, or [[codon]]. Scientists knew there were a total of four bases ([[guanine]], [[cytosine]], [[adenine]], and [[thymine]]). They also knew that were 20 known [[amino acids]]. [[George Gamow]] suggested that the genetic code was made of three nucleotides per amino acid. He reasoned that because there are 20 amino acids and only four bases, the coding units could not be single (4 combinations) or pairs (only 16 combinations). Rather, he thought triplets (64 possible combinations) were the coding unit of the genetic code. However, he proposed that the triplets were overlapping and [[Genetic code#Degeneracy|non-degenerate]].<ref name="Leavitt_craze">{{cite web |last= Leavitt |first=Sarah A.|title=Deciphering the Genetic Code: Marshall Nirenberg. The Coding Craze |url=http://history.nih.gov/exhibits/nirenberg/HS3_craze.htm |publisher=Stetten Museum, Office of NIH History |year=2004 |accessdate=2009-10-05 |url-status=live |archive-date=9 February 2020 |archive-url=https://web.archive.org/web/20200209101250/https://history.nih.gov/exhibits/nirenberg/HS3_craze.htm}}</ref> [[Seymour Benzer]] in the late 1950s had developed an assay using phage mutations which provided the first detailed linearly structured map of a genetic region. Crick felt he could use mutagenesis and genetic recombination phage to further delineate the nature of the genetic code.<ref>{{Cite journal| doi= 10.1016/j.cell.2007.02.029| author= Yanofsky C.| year = 2007|title = Establishing the Triplet Nature of the Genetic Code| journal = Cell |volume = 128| issue= 5 | pages = 815β818| accessdate = 2018-01-24| url = http://www.cell.com/cell/pdf/S0092-8674(07)00253-X.pdf | pmid= 17350564| doi-access = free}}</ref> In the [[Crick, Brenner et al. experiment]], using these phages, the triplet nature of the genetic code was confirmed. They used [[frameshift mutation]]s and a process called [[mutation#Classification of mutation types|reversions]], to add and delete various numbers of nucleotides.<ref>{{Cite journal| doi= 10.1038/1921227a0|author1=Crick F.H.C. |author2=Brenner S. |author3=Barnett L. |author4=Watts-Tobin R.J. |name-list-style=amp | year = 1961|title = General Nature of the Genetic code for Proteins| journal = Nature|volume = 192 | pages = 1227β1232| accessdate = 2009-10-10| url = https://profiles.nlm.nih.gov/SC/B/C/B/J/_/scbcbj.pdf| pmid= 13882203| issue=4809| bibcode=1961Natur.192.1227C|s2cid=4276146 }}</ref> When a nucleotide triplet was added to or deleted from the DNA sequence, the encoded protein was minimally affected. Thus, they concluded that the genetic code is a triplet code because it did not cause a frameshift in the reading frame.<ref>{{Cite journal| doi = 10.1073/pnas.48.4.666| author = Matthaei, H.J., Jones, O.W., Martin, R.G., and Nirenberg, M.W. | title = Characteristics and Composition of RNA Coding Units | journal=Proceedings of the National Academy of Sciences of the United States of America | volume = 48 | pages =666β677 | year = 1962| pmid = 14471390| pmc = 220831| issue = 4 |bibcode = 1962PNAS...48..666M | doi-access = free }}</ref> They correctly concluded that the code is degenerate, that triplets are not overlapping, and that each nucleotide sequence is read from a specific starting point.
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